If there is one joint that quietly determines how we age, it is the knee. Knees play a key role on overall health and longevity. Let me explain why.

The knee is the largest joint in the body and yet most of us don’t give it a second thought in our daily lives until it begins to hurt. When we think about longevity, we should be thinking about knees far more than we do. Because a strong, stable knee is not merely a convenience, it is a predictor of independence, metabolic health, cognitive engagement and even mortality.

But before we discuss what goes wrong, let us start with what the knee actually is. Because understanding the machine helps us understand its weaknesses and how it can fail.

Knee Anatomy 101

The knee is not a simple hinge, despite appearances. It is a complex, weight-bearing synovial joint where the femur (thigh bone) meets the tibia (shin bone), with the patella (kneecap) gliding in front. Between the bones sit two crescent-shaped pads of cartilage called menisci, which act as shock absorbers and stabilisers. Criss-crossing inside and around the joint are four major ligaments: the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL) and lateral collateral ligament (LCL), all of which hold the joint together under extraordinary loads. Surrounding everything is a capsule lined with synovial membrane, producing fluid that lubricates and nourishes the cartilage. And overarching the entire structure are the quadriceps, hamstrings and calf muscles, which generate and control movement.

Every step you take, every time you stand from a chair, every mile you walk, your knee absorbs forces equivalent to several times your body weight.

This is why the knee matters so profoundly for longevity. Mobility is the substrate of healthy ageing. When knees fail, people stop walking. When they stop walking, muscle mass drops, cardiovascular fitness declines, balance deteriorates, social engagement shrinks and the risk of falls and fractures rises sharply. A 2019 study in the Journal of the American Geriatrics Society found that knee pain and dysfunction were independently associated with faster declines in physical function and higher mortality risk in older adults. The knee is not an isolated joint, but the key to an active life.

So what goes wrong? And why?

The problems that develop in knees over time fall into two broad categories, which is a useful framework for thinking about them. The first is degenerative wear, the slow, cumulative damage that comes from living in a body that is subject to gravity, load and time. The second is acute structural injury, the sudden tears, ruptures and dislocations that happen in sport, in falls, or sometimes in the simple, unlucky twist of an ordinary day.

Osteoarthritis sits at the top of the degenerative list. It is the wearing away of articular cartilage, the smooth, gliding surface that covers the ends of the bones. As cartilage thins, the underlying bone can thicken, cysts can form, and the joint can become inflamed, painful and stiff. It is not, as people often assume, simply caused by “wear and tear” in the mechanical sense. The biology is more nuanced. Low-grade chronic inflammation, metabolic factors, prior injuries, obesity and genetics all play roles. Adipose (fat) tissue is not inert; it secretes inflammatory cytokines that can accelerate joint degradation. This is partly why obesity is such a powerful risk factor; it is not just the extra load, but the systemic inflammatory environment.

Meniscal tears are extraordinarily common, particularly after the age of forty. The menisci become more brittle and less elastic with age. A tear can happen acutely during sport, but just as often it occurs during an innocuous movement such as a squat or a twist while getting out of a car. In younger people, meniscal tears are typically traumatic. In older adults, they are often degenerative, the result of tissue that has simply become less resilient over decades.

Then there are the ligament injuries. ACL ruptures are the headline event in sports medicine, often requiring surgical reconstruction in active individuals. MCL sprains are common in contact sports and usually heal well with conservative management. PCL and LCL injuries are less common but can be serious. The prognosis for ligament injuries depends heavily on age, activity level and whether the injury is isolated or combined with other damage, such as meniscal tears or cartilage injury, the so-called “unhappy triad” of ACL, MCL and medial meniscus damage.

Patellofemoral pain syndrome (pain around or behind the kneecap) is one of the most common knee complaints in younger and middle-aged adults. It is typically driven by biomechanical factors: muscle imbalances, poor tracking of the patella in its groove or overuse. It is rarely dangerous, but it can be stubborn and functionally limiting.

Tendinopathies (such as patellar tendinopathy, or jumper’s knee) and bursitis (inflammation of the fluid-filled sacs that reduce friction) round out the common problems. These are often overuse injuries, linked to repetitive loading, poor load management or muscular weakness.

Why do these problems accelerate with age? The reasons are multifactorial. Cartilage has a poor blood supply and limited capacity for repair. With age, the synthesis of collagen and proteoglycans (the molecules that give cartilage its resilience) declines. Synovial fluid becomes less viscous. Muscles lose mass and strength unless actively maintained. Proprioception (the body’s sense of where the joint is in space) dulls. And for many people, activity levels drop, which paradoxically hastens decline because cartilage is nourished by the cyclical loading and unloading of movement. The knee does not like being still. Nor does it like being overloaded. It likes being used, intelligently, within a window of tolerance.

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So what can we do to keep our knees in great shape?

The evidence here is clearer than many people realise, and it does not require exotic interventions. Strength training is the single most powerful protective factor. The quadriceps, in particular, act as shock absorbers for the knee. Strong quadriceps reduce the load transmitted directly to cartilage and ligaments. Resistance training, progressive and well-programmed, has been shown to reduce pain and improve function even in people who already have radiographic osteoarthritis. It is never too late to start, though earlier is better.

Weight management is equally critical. For every kilogram of body weight lost, the load on the knee during walking decreases by roughly four kilograms. The metabolic benefits of reducing adipose tissue (which lowers systemic inflammation) are an added bonus.

Movement quality matters. How you squat, how you walk, how you descend stairs, whether your hips and ankles move well enough to spare your knees from compensatory strain. These are not trivial details, they are the mechanics of longevity. Working with a knowledgeable physiotherapist or strength coach to address biomechanical deficits can be transformative.

Low-impact cardiovascular exercise, such as cycling, swimming, brisk walking on forgiving surfaces maintains the health of cartilage, synovium and bone without the repetitive pounding of running on hard surfaces, particularly if you are carrying excess weight or already have early degenerative changes.

It is a myth that you only have so many steps in your knees before they wear out. Yes some activities can do permanent damage to the knees (such as competitive mogul skiing) but using your knees sensibly can help them to regenerate. The evidence is more robust than many people realise. But as with most things in physiology, the answer is not a simple yes or no. It depends on dose, history and individual context.

The most useful framework here is a U-shaped risk curve. At one extreme, sedentary living is strongly associated with knee osteoarthritis. At the other extreme, elite competitive running at very high volumes also carries elevated risk. Between those extremes lies a broad chondroprotective window where recreational running appears not merely safe, but actively beneficial.

A landmark systematic review and meta-analysis of over 125,000 individuals found that recreational runners had a knee and hip osteoarthritis prevalence of just 3.5%. Sedentary controls, by comparison, sat at 10.2%, nearly three times higher. Elite and ex-elite competitive runners were at 13.3%.

This is not a marginal finding. It has been replicated across multiple large cohorts, including a survey of 3,804 Chicago Marathon participants, where the prevalence of hip or knee arthritis was 7.3%, far below the approximately 26% seen in the general population over the age of 45.

Critically, in that marathon cohort, the number of marathons completed, cumulative years of running, weekly mileage and running pace were not significant predictors of arthritis. The real risk factors were age, BMI, previous injury or surgery and family history.

So why does running protect the knee rather than destroy it?

The first part of the answer is biomechanical. Runners generate higher peak forces per step than walkers, but they take fewer steps per kilometre due to longer strides and flight phases. The cumulative load per unit of distance may actually be comparable to, or in some models even lower than, walking.

Furthermore, cartilage is viscoelastic, i.e. it responds to the rate of loading. The high loading rates of running increase the dynamic stiffness of cartilage, which limits internal deformation and protects the collagen network from excessive strain.

The second part of the answer is biological. Cartilage has no blood supply. It is nourished by the cyclical compression and release of movement, which pumps synovial fluid into the tissue and washes metabolic waste products out. Running appears to facilitate exactly this. Studies show that a 30-minute run decreases the concentration of pro-inflammatory cytokines such as IL-1β and TNF-α in synovial fluid, while increasing lubricin production (the molecule that reduces friction within the joint.)

Running also increases serum cartilage oligomeric matrix protein (sCOMP), which was once viewed purely as a damage marker but is now understood to reflect active cartilage metabolism and tissue turnover.

MRI studies confirm that cartilage undergoes transient deformation immediately after running (a reduction in volume and thickness of roughly 3–5%) but returns to baseline within 1 to 24 hours.

The absence of new structural damage even after a marathon suggests that cyclic mechanical loading, within physiological limits, is well tolerated by healthy cartilage.

What about people who already have osteoarthritis? Here, the evidence is equally reassuring. A study using data from the Osteoarthritis Initiative found that running did not increase the risk of symptom exacerbation or structural progression (measured by joint space narrowing) over 48 months in individuals over 50 with radiographic knee osteoarthritis. Runners with osteoarthritis actually reported significant pain reduction compared with non-runners.

So does running regenerate cartilage? That is a strong word, and we should be careful with it. The evidence does not show that running creates new cartilage where it has been lost. What it does show is that moderate, recreational running maintains cartilage health, stimulates metabolic turnover, reduces inflammation, improves joint lubrication and (through the strengthening of quadriceps and other supporting musculature) reduces the load that cartilage must bear. In that sense, running preserves and conditions the knee’s existing architecture. Some imaging studies have even found that long-distance runners develop thicker, more resilient cartilage over time. Whether this constitutes true regeneration or adaptive remodelling is a semantic distinction; the practical outcome is healthier joint tissue.

The caveats matter. If you are significantly overweight, have a history of knee injury or surgery, or already have advanced structural damage, running may not be the optimal first intervention. The knee absorbs forces equivalent to five to ten times body weight with each step. If you are carrying excess weight or have compromised cartilage, those forces may exceed the joint’s tolerance. In such cases, beginning with low-impact conditioning, weight management and strength training is the wiser path.

The dose also matters. The protective effect appears to sit within what researchers call the “biomechanical window”, which is roughly 1.5 to 5.9 METs^[1] of activity. Recreational running fits neatly here. Competitive volumes exceeding 90 kilometres per week for many years push into the zone where risk rises.

The idea that running wears out your knees is one of the most persistent myths in medicine, and it is largely wrong. For most people, running within reason is not merely safe but one of the most effective, accessible and well-evidenced strategies for maintaining knee health over a lifetime. It is not a magic bullet that will rebuild destroyed cartilage, but it is a powerful tool for preserving what you have, stimulating the biological machinery of the joint and keeping the muscles that protect your knees strong and responsive.

Nutrition plays a supporting role. Adequate protein supports muscle and connective tissue repair. Omega-3 fatty acids have modest anti-inflammatory effects. Vitamin D and calcium matter for bone health. Glucosamine and chondroitin have mixed evidence; some people report benefit, but large trials have been underwhelming. They are not harmful for most, but they are not a substitute for the fundamentals.

Now, what about when prevention is not enough? What about the latest therapies?

This is where the topic becomes as nuanced as the one about peptides. There is genuine excitement in regenerative and surgical orthopaedics, but there is also a great deal of hype, commercial pressure and premature marketing.

Corticosteroid injections have been the workhorse of knee pain management for decades, and they remain useful in specific contexts. A corticosteroid injection into the knee can dampen inflammation rapidly and provide meaningful short-term relief, typically weeks to a few months, for flare-ups of osteoarthritis or bursitis. For someone in acute pain who cannot sleep, walk or participate in physiotherapy, this can be a valuable bridge. But the evidence for long-term benefit is poor, and the safety profile is more concerning than many patients realise. Repeated steroid injections have been associated with accelerated cartilage loss, tendon weakening and, in some cases, joint infection or bone damage. The American College of Rheumatology now advises caution with frequent injections and current guidelines suggest they should not be administered more than three to four times per year, if at all. They are a symptom-management tool, not a disease-modifying one. If you are receiving steroid injections every few months for years, you are likely masking a problem that needs a different solution.

Hyaluronic acid injections aim to restore the lubricating properties of synovial fluid by injecting a synthetic or purified form of the molecule directly into the joint. The theory is elegant: osteoarthritic joints comprise degraded, less viscous fluid, so replacing it should reduce friction and pain. The reality has been underwhelming. Large-scale trials and meta-analyses have shown, at best, modest and inconsistent benefits compared to placebo, and some major guideline bodies, including the American Academy of Orthopaedic Surgeons, have recommended against their routine use. They are not harmful for most people, but they are expensive, the effect is unpredictable, and the evidence does not support them as a first-line intervention. Some patients report genuine relief, and individual response does vary, but from a population perspective, hyaluronic acid sits in a grey zone, not clearly effective enough to recommend broadly, not dangerous enough to ban. It is another example of a therapy that sounds more biologically compelling than the clinical data supports.

Against this backdrop of modest conventional options, the appeal of regenerative therapies becomes easier to understand, even if their promise, too, is often overstated.

Platelet-rich plasma (PRP) involves concentrating platelets from the patient’s own blood and injecting them into the joint or around injured tissue. The theory is that growth factors released by platelets may stimulate healing. The evidence is mixed and highly variable depending on the condition. For early to moderate knee osteoarthritis, some well-conducted trials show modest improvements in pain and function compared to placebo, particularly in younger patients with less advanced disease. For meniscal tears or ligament injuries, the evidence is weaker. PRP is probably not the breakthrough it is sometimes marketed as, but it may have a role as part of a broader management strategy for specific patients.

Stem cell therapy, using mesenchymal stem cells, often derived from bone marrow or adipose tissue, has generated enormous interest. The premise is alluring: introduce cells that can differentiate into cartilage, modulate inflammation and regenerate tissue. The reality is more complicated. Early human trials have shown some promise in reducing pain and perhaps slowing structural progression in osteoarthritis, but high-quality, long-term data is still lacking. The field is also plagued by inconsistent protocols, unregulated clinics offering expensive treatments with little oversight and a gap between animal studies and human outcomes. Stem cells may well become a cornerstone of orthopaedic medicine in the future. They are not there yet.

Exosome therapy is even earlier in its development. Exosomes are extracellular vesicles that carry signalling molecules between cells (read my earlier article on this topic). The idea is that they can deliver regenerative instructions without the risks of live cell therapy. It is a fascinating area of research, but currently the clinical evidence for knee osteoarthritis or injury is preliminary. Anyone paying for exosome injections for their knees is participating in an experiment, not receiving an established treatment.

Knee replacement surgery. Total or partial arthroplasty is, by contrast, one of the great success stories of modern medicine. For end-stage osteoarthritis where pain is severe and function is profoundly limited, knee replacement can be transformative. Modern implants, improved surgical techniques and enhanced recovery protocols have made the procedure safer and more effective than ever. The vast majority of patients experience dramatic pain relief and improved mobility. However, replacements have a finite lifespan (typically fifteen to twenty years) and revision surgery is more complex. This makes timing important. A knee replacement is not a first resort, and it is not a reason to neglect prevention. But when conservative measures have been exhausted, it is a genuinely life-altering intervention.

Other emerging approaches include autologous chondrocyte implantation and matrix-induced chondrogenesis for focal cartilage defects in younger patients, as well as biologic scaffolds and tissue engineering approaches that remain largely experimental. There is also growing interest in sensorimotor training, blood-flow restriction therapy and personalised biomechanical interventions guided by motion capture and artificial intelligence. These are exciting frontiers to keep an eye on.

So the take-home from all of this is that your knees deserve the same disciplined, evidence-based attention that we give to our diets, our sleep and our cardiovascular health. Do not wait for pain to force the conversation. The knee is not a passive hinge that inevitably wears out like a car tyre. It is a living, adaptive tissue that responds to how you load it, how you nourish it and how you care for the muscles around it.

Do not be seduced by the idea that an injection of stem cells or PRP will undo years of neglect. These therapies may have roles, but they are not substitutes for strength, weight management and intelligent movement. And if the time comes that your knee needs surgical intervention, know that modern arthroplasty is remarkably effective but that the best outcome is still the one where you never need it at all.

The future of knee longevity will depend not on miracle injections, but on better public understanding of biomechanics, earlier intervention with strength and lifestyle modification and a much more disciplined conversation about which regenerative therapies are proven versus which are merely plausible. Your knees have carried you this far. With the right care, they can carry you a great deal further.

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^[1] Metabolic Equivalent of Task. One MET is the energy you burn while resting or sitting still.

There’s a new buzz word that has been doing the rounds in the longevity community lately and that word is exosomes. There’s plenty of excitement about them and their role in rejuvenating the body, but what exactly are they?

You can think of them as the body’s microscopic postal service: tiny bubble‑like packages that cells use to send messages to one another across tissues and even organs. Almost all cells in the body can release small membrane‑bound vesicles (little spheres of fat with cargo inside) into the fluids around them. Exosomes are one specific type of these vesicles, typically far smaller than a single cell. They form inside cells in specialised “sorting compartments” and are then released when those compartments fuse with the cell surface.

Inside each bubble is a custom mix of molecules from the parent cell, such as pieces of protein, genetic material (like DNA and RNA) and other instructions.

Exosomes circulate throughout the body and they have been found in blood, urine, saliva, breast milk and cerebrospinal fluid. This means that they have access to many tissues throughout the body. When they fuse with another cell, they deliver that cargo and can re‑programme what the recipient cell is doing.

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Why exosomes matter

The simplest way to think about exosomes is as a parallel communication channel layered on top of hormones, nerves and immune signals. Instead of sending a single molecule like insulin, a cell can ship a whole “data packet” containing dozens of proteins and RNAs at once. That makes exosomes powerful tools for coordinating complex responses such as wound healing, immune activation or tissue remodelling.

Crucially, exosomes can be “good” or “bad”. Their impact depends entirely on who sent them and what they contain. For example, exosomes are “bad” when tumour cells release them to help prepare distant tissues for metastasis, suppress immune responses or promote blood vessel growth around a cancer. They are “good” when they are released by stem cells or healthy tissue to carry pro‑repair signals that support regeneration after a heart attack, stroke or other injury.

Exosomes, ageing and the “senescent microenvironment”

Ageing is increasingly seen as a systems‑level process rather than just wear and tear on individual parts. Exosomes fit neatly into that systems story. Several lines of evidence now suggest that they participate in the spread of ageing signals between cells and tissues.

One key player here is cellular senescence, which are cells that have permanently exited the cell cycle and adopt a pro‑inflammatory, pro‑remodelling secretory profile. Senescent cells (sometimes nick-named “zombie” cells) shed exosomes loaded with distinct cargo. Experimental work has shown that exosomes from senescent cells can induce senescence‑like changes in otherwise young cells.

This suggests exosomes help create a “senescent microenvironment”, where small numbers of damaged cells can influence their neighbours and potentially propagate dysfunction at a distance. In parallel, exosome‑associated microRNAs have been implicated in regulating tissue repair, inflammation and resilience to stress, with some specific microRNAs linked to age‑related diseases and possibly longevity.

Potential applications of exosomes

• Biomarkers of biological ageing: Because exosomes carry a fingerprint of the parent cell’s state, changes in their cargo over time may reflect underlying biological age rather than just chronological age. Studies have reported age‑related shifts in exosomal proteins and microRNAs associated with cardiovascular disease, neurodegeneration and osteoarthritis.

• Mediators of age‑related disease: Exosomes appear to participate in the development of atherosclerosis, heart failure, neurodegeneration and metabolic disease, often by modulating inflammation, endothelial function and cell death pathways.

• Tools for “reprogramming” tissues: If exosomes can carry pro‑youthful, pro‑repair signals, it may be possible to harness them therapeutically, either by collecting and concentrating exosomes from beneficial sources (for example, certain stem cells) or by engineering exosomes to carry defined cargo. This has led to interest in exosome‑based approaches as a kind of “cell‑free” regenerative therapy.

Regenerative medicine: promise and current evidence

One of the most active areas for exosome research is regenerative medicine. Animal studies and early human work suggest that exosomes derived from mesenchymal stem cells, cardiac progenitors and other sources can reduce inflammation, promote angiogenesis (blood vessel growth) and support tissue repair after injury.

A number of early‑phase clinical trials have explored exosome use in conditions such as heart disease, stroke, skin wounds and immune‑mediated disorders. Other trials are focusing on exosomes as biomarkers, for instance, using circulating exosomal signatures to predict prostate cancer risk or stroke outcomes.

But the clinical landscape is still sparse and the field is young, heterogeneous and not yet ready to support broad claims of “exosome therapy” as a proven anti‑ageing intervention.

The science versus the hype

As with peptides, the gap between laboratory findings and commercial offerings is wide. Exosomes are now being marketed in various guises, from intravenous infusions to cosmetic products and “exosome facials”. Regulatory agencies have begun to issue warnings about unapproved exosome therapies, particularly those advertised for joint pain, neurodegenerative disease or general “rejuvenation”.

The concerns are based around 3 areas:

• Source and quality control: Genuine exosome preparations require careful isolation, characterisation and testing to ensure they contain the intended vesicles and are free from contaminants. Many commercial products provide little transparency about their origin, dose or composition.

• Mechanistic uncertainty: Even for research‑grade preparations, the mechanisms of action are not fully understood. Different cell sources, culture conditions and isolation methods can yield exosomes with very different cargo and effects.

• Safety and off‑target effects: Exosomes can carry complex signalling cocktails. While that opens therapeutic possibilities, it also raises the risk of unintended consequences, such as promoting fibrosis, abnormal angiogenesis or immune dysregulation in some contexts.

For now, exosomes belong firmly in the experimental category: fascinating as a biological tool and a research‑grade therapeutic candidate, but not a mature, validated longevity therapy ready for widespread use.

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Fisetin has become one of the more talked-about compounds in longevity science. In mice, it looks impressive: it helps clear senescent cells, improves physical function and even extends lifespan in some studies.

But in humans, the story is very different. Despite serious interest from the National Institute on Aging (NIA) in the US and other researchers, the current trial data has not shown clear, reliable benefits on health, frailty or biological ageing.

What Is Fisetin?

Fisetin is a natural flavonoid found in small amounts in foods such as strawberries, apples, onions and persimmons. It has attracted attention because it appears to act as a senolytic, meaning it may help remove senescent cells, the damaged “zombie cells” that build up with age.

In theory, that sounds very promising. Senescent cells contribute to inflammation, tissue dysfunction, and many age-related diseases, so a compound that can reduce them could, in principle, help people age more healthily.

The problem is that “works in theory” and “works in humans” are very different things.

Why the Excitement Started

The interest in fisetin really took off after animal studies showed meaningful benefits. In mice, intermittent fisetin treatment reduced frailty, improved grip strength and increased healthspan.

That is exactly the kind of result longevity researchers hope to see. It suggested that fisetin might do more than just act like a generic antioxidant. It might actually influence one of the core biological processes of ageing.

So naturally, researchers moved into human trials.

What the Human Trials Show

This is where the picture becomes much less exciting. NIA-related and NIA-supported studies have tested fisetin in older adults, including frail breast cancer survivors and healthy older adults, to see whether it can improve function, vascular health or markers of cellular ageing.

So far, the human evidence has not shown a convincing benefit. A small pilot study in healthy adults over 50 found mixed results: 4 out of 10 participants had lower biological age scores, 5 had higher scores and 1 had no change.

That is not the kind of signal you would want if you were trying to prove fisetin is a reliable anti-ageing intervention. The authors of that pilot study were explicit that fisetin should not be recommended as an anti-ageing agent until more extensive studies are done.

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Why It Works in Mice but Not in People

There are several likely reasons why the results in mice were more positive:

First, mice and humans are not the same biology. Mice age faster, live shorter lives and may respond to senolytic compounds in a way that is easier to detect over a short period.

Second, the dosing problem is huge. What works in a mouse may require a very different exposure in a human. The amount of fisetin used in animal experiments is not easily translated into a safe or practical human dose.

Third, human ageing is far more complex. By the time someone reaches older age, decades of inflammation, metabolic stress, medication use, lifestyle differences and chronic disease can blur the effect of any one compound. A supplement that looks dramatic in a controlled mouse study may produce only a tiny or undetectable effect in real-world humans.

What This Means In Practice

At the moment, fisetin is still an interesting research compound, not a proven anti-ageing treatment. The available human trials do not support the idea that it reliably improves health or reverses ageing in people.

That does not mean the science is useless. It means the hype is ahead of the evidence. The animal data justifies more research, but it does not justify strong claims yet.

Fisetin is a good example of how promising longevity compounds can look in preclinical studies and still fail to deliver clear results in humans. In mice, the signal is strong. In people, the signal is weak, inconsistent or absent so far.

Fisetin remains scientifically interesting, but it has not yet shown convincing health benefits in humans. So I would suggest that you give fisetin a miss and spend your money on other longevity supplements that are supported by stronger evidence of delivering health benefits.

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Peptides are having a major moment in health and longevity circles, but the conversation is far more nuanced than the hype suggests. When we hear the word peptides, we shouldn’t be thinking of them as a single category, but as biologically distinct compounds with very different levels of evidence, safety and clinical relevance.

But beyond the hype, what actually are peptides? To answer this, let’s start with explaining what proteins are.

Our bodies are made up of proteins. There are an estimated 20,000 core unique proteins in the human body. Our DNA is our master architectural blueprint stored in every cell, and our body uses this blueprint to make the proteins we need. The physical infrastructure of our bodies is made up of proteins, as well as our enzymes, ATP, hormones, neurotransmitters, antibodies, haemoglobin, lipoproteins, etc. you get the picture.

Every single thing you are, feel or do is enabled by proteins.

Proteins are made up of smaller building blocks called amino acids. There are 20 of these amino acids in total that the body uses to build proteins, 9 of which are considered essential amino acids, meaning that we must get them from our foods as our body can’t make them. These amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. Animal proteins are the best sources of the essential amino acids, as well as some soy products such as tofu and edamame.

There are also 11 non-essential amino acids, namely alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine and tyrosine. Some of these are classified as conditionally essential, meaning that they become essential if you are ill or stressed. Those interested in the chemical structure of each amino acids can click the link here.

So I’ve described proteins and amino acids, but what about peptides? To put it in the simplest terms, a peptide is the name given to a chain of amino acids held together by a peptide bond, hence the name given to them. They can be considered to be small proteins – typically a protein comprising fewer than 50 amino acids is called a peptide. See diagram below.

You can think of peptides as tiny, specific fragments of the larger proteins the body uses to build and repair itself. If a protein is a long, complex sentence, a peptide is just a short, powerful phrase, i.e. a small chain of amino acids. Because they’re small, the body can use them as precise messengers, telling certain cells to do specific jobs like reduce inflammation, build collagen for skin or stimulate muscle repair.

In the world of longevity and health, peptides are exciting because they can target one process at a time, with fewer side effects than broader drugs. For example, some peptides may signal the body to release more growth hormone, while others help calm an overactive immune system. However, because peptides are fragile, most can’t survive digestion as a pill if swallowed, which is why they often need to be injected or applied as a cream to work properly.

One useful framework is to split peptides into two broad groups. The first includes peptides with known receptors and clearer downstream effects, such as the GLP-1 receptor agonist drugs (the likes of Ozempic and Mounjaro). These have the strongest clinical footing and are already transforming metabolic health, weight loss and diabetes care.

The second group includes peptides with intriguing animal data but limited human evidence, unclear mechanisms and uncertain safety profiles. This is where much of the current excitement (and confusion) lies.

BPC-157 is probably the most famous of these peptides. Originally identified from gastric tissue, it was first associated with gut protection and later became popular for tendon, ligament, nerve and injury repair. In animals, the results can look impressive: faster wound healing and improved tissue repair. But the human evidence remains thin, and there are major unresolved questions about dosage, pharmacokinetics, receptor biology and long-term safety. It is the gap between promise and proof that makes this peptide so controversial.

Some peptides may be doing more than simply “reducing inflammation.” BPC-157 appears to promote healing by influencing blood flow, growth factor signalling, tissue remodelling and cellular migration. That makes it interesting but also raises caution. A compound that broadly increases repair signalling could theoretically have trade-offs, especially if it affects angiogenesis or other pathways that are not always desirable.

Beyond BPC-157, there are several other peptides that have gained attention in longevity and sports performance communities. GHK-copper is being used for skin, hair and collagen-related goals. Pinealon (a synthetic tri-peptide developed in Russia) and epitalon/epithalon (comprising four amino acids) are often discussed in the context of sleep, cognition, DNA repair and ageing.

There are also thymus-related peptides that are framed as part of the larger story of immune ageing, especially as thymic function declines with age. Each of these compounds has its own story, but the common thread is the same: there is often more enthusiasm than evidence.

Peptides are now deeply entangled with compounding pharmacies, telehealth platforms, grey-market sellers and regulatory uncertainty. In some cases, products are marketed aggressively before the science is mature. In others, the legal status changes faster than clinical practice can adapt. That creates a space where patients may be exposed to products that are not well studied, not consistently manufactured and not always clearly prescribed.

My overall message to you, dear reader, is not to consider all peptides the same. GLP-1s belong in a very different category to BPC-157, and both belong in a very different category to the more speculative anti-ageing peptides that have little modern clinical validation. Don’t think of peptides as one breakthrough, but a collection of very different tools, each with its own evidence base, risks and open questions.

Peptides are an exciting frontier in biomedicine, but excitement is not evidence. The future of peptide medicine will depend on better pharmacology, better clinical trials, clearer regulation and a much more disciplined conversation about what is proven versus what is merely plausible.

3D structure of glucagon-like peptide 1 (GLP-1)

Source: AlphaFold

Recently Dr Peter Attia, a US-based longevity doctor did a podcast on sleep medications. I found it particularly interesting and wanted to share some of his key points as sleep is one of the most non-negotiable processes in human biology and most people with sleep issues are not aware of the basic four mechanisms of sleep, which makes it difficult to diagnose and treat their sleep issues effectively.

This article does not discuss sleep hygiene; I wrote a short article on that a while ago. Subscribers can read it here.

The four pillars of sleep disruption

Sleep is regulated by four distinct but interrelated systems, and almost every sleep issue can be traced back to one or more of these. The first is sleep pressure, the homeostatic drive that accumulates the longer we remain awake and discharges during sleep. The second is circadian timing, the internal clock anchored to the light-dark cycle and coordinated by melatonin and cortisol. The third is hyperarousal, a state of elevated cortical and neuroendocrine activity that overrides the normal drive to sleep. The fourth is sleep architecture, the quality and structure of the sleep stages we actually obtain.

Most treatment failures occur when a perfectly valid intervention is applied to the wrong mechanism. A sedative-hypnotic may reduce sleep latency in someone whose primary problem is circadian misalignment, but it will not correct their clock. Conversely, circadian interventions such as timed light exposure will do little for a patient whose insomnia is driven by hyperarousal.

Even the most precisely targeted sleep medication is a temporary measure if an unrecognized medical condition is driving the problem. Three conditions are frequently overlooked in clinical practice.

1) Restless leg syndrome. This affects approximately 3% of adults worldwide. It presents as an irresistible urge to move the legs during rest, often accompanied by crawling or tingling sensations that temporarily abate with movement. It disrupts sleep onset and frequently masquerades as primary insomnia.

2) Obstructive sleep apnoea. This is even more prevalent. Because of the obesity epidemic, roughly a third of US adults are likely to have it. Sleep apnoea is characterized by snoring, gasping or apnoeic episodes during sleep. Patients typically report unrefreshing sleep, morning headaches and excessive daytime sleepiness despite adequate time in bed.

3) Mood and anxiety disorders. These can affect up to a third of adults. Persistent depressive disorder can produce either insomnia or hypersomnia. Anxiety disorders fragment sleep maintenance. Bipolar disorder is marked by circadian disruption that feeds a vicious cycle with the disease itself. Up to 45% of people with mood or anxiety disorders report severe insomnia.

All of these have established medical and behavioural treatments and addressing them can improve sleep with substantial downstream benefits. But when the underlying cause has been ruled out or addressed and sleep remains impaired, pharmacological tools may have a role.

There are three classes of drugs, with three very different outcomes:

Benzodiazepines (Benzos): sedation without restoration

Benzodiazepines include drugs such as temazepam, lorazepam, alprazolam, diazepam and clonazepam. These remain among the oldest and most widely recognized sedative-hypnotics. They enhance signalling through GABA-A receptors, the brain’s principal inhibitory neurotransmitter system, effectively pressing the brakes on the hyperarousal that characterizes much of modern insomnia. In the thalamus, where GABAergic signalling is increased, the sensory gate between the external world and the cortex closes more tightly and conscious perception fades.

Benzos reduce sleep latency and may modestly increase total sleep time, but they significantly alter sleep architecture, often decreasing slow-wave sleep and suppressing REM (dream) sleep. They are potent anxiolytics (anti-anxiety), which makes them useful in acute crises where ruminative thought and somatic tension are the primary barriers to sleep. But the trade-offs are substantial.

These drugs carry genuine risks of physiologic dependence and withdrawal, including rebound insomnia, anxiety and in severe cases, seizures. They increase fall risk through dizziness, ataxia and impaired balance. Taking benzos with alcohol or opioids enhances the GABAergic signalling or depress respiratory centres, markedly increases the risk of respiratory depression and death, particularly in patients with undiagnosed obstructive sleep apnoea.

There is also a meaningful signal of cognitive impairment with long-term use, affecting psychomotor speed, executive function, memory and processing speed. They can also trigger complex sleep-related behaviours, such as sleepwalking and cause anterograde amnesia. This amnesia is both a feature and a bug: patients forget nocturnal awakenings, so they feel as though they slept solidly when objective measures show fragmented sleep. The subjective impression of benefit exceeds the physiological reality.

The labels recommend two to four weeks of use. Meta-analyses show the average duration is nearly a decade. The way to think about benzos is this: they are highly effective at shutting down hyperarousal in the short-term, but they do so at the cost of sleep quality, dependence risk and cognitive side effects. They solve the immediate problem, but they often create a larger one if used chronically.

Z-drugs: a cleaner mechanism, but not a clean solution

The concerns around benzos drove the development of the so-called Z-drugs, namely zolpidem (Ambien), zaleplon (Sonata) and eszopiclone (Lunesta). Together, they account for over 40% of all sleep medication prescriptions in the United States, with Ambien alone representing nearly 90% of that market!

Despite lacking structural similarity to benzos, Z-drugs also act on GABA-A receptors. They are more selective for sleep promotion and have less prominent anxiolytic and muscle-relaxing effects than classic benzos. They reduce sleep latency and modestly increase sleep time. Their pharmacokinetic profiles differ in clinically meaningful ways: Lunesta, with a half-life of approximately six hours, is suitable for both sleep-onset and sleep-maintenance insomnia; Ambien’s intermediate-release formulation favours sleep-onset problems; Sonata, with a half-life of about one hour, can even be used in the middle of the night if the patient wakes with sufficient time remaining before morning.

It is often claimed that Z-drugs have less impact on sleep architecture than benzos, with smaller effects on slow-wave and REM sleep. But much of this favourable picture comes from animal studies and has been contested in human evidence. Moreover, chronic use at higher doses is associated with more pronounced architectural disruption. And crucially, Z-drugs also induce anterograde amnesia.

The complex sleep behaviours associated with Z-drugs are not trivial. Sleepwalking, sleep-eating, sleep-shopping, sleep-driving, sleep-sex and phone calls made in a dissociated state have all been documented. In 2019, the FDA issued a black box warning about these behaviours, which have resulted in accidental overdoses, falls, burns, near-drownings, carbon monoxide poisonings, motor vehicle collisions with the patient driving, and self-injuries including gunshot wounds and apparent suicide attempts. These effects are most likely at higher doses in older adults or when combined with alcohol or other sedatives. More than half of users of sleeping medications use at least one additional sedating agent and 10% take three or more.

Z-drugs were designed to be a cleaner version of benzos but in practice many of the same issues remain. They can help with sleep onset in the short-term, but they still carry meaningful risks around memory, behaviour and dependence. They should be used at the lowest effective dose for the shortest possible duration, and only with a parallel plan for addressing the underlying causes of insomnia and offering cognitive behavioural therapy for insomnia (CBT-I).

DORAs: working with biology rather than against it

This brings us to the newest and arguably the most exciting class of sleep medications: the dual orexin receptor antagonists, or DORAs. Currently available agents include daridorexant (Quviviq), lemborexant (Dayvigo) and suvorexant (Belsomra).

DORAs are different in a way that matters fundamentally. Most traditional sleep medications work by forcing sedation. They broadly suppress brain activity. DORAs do not do this. They work by dialling down one of the brain’s primary wakefulness systems (the orexin system) thereby allowing natural sleep processes to take over. That distinction between forcing sleep and allowing sleep is not semantic. It shows up in the outcomes.

In head-to-head comparisons, DORAs outperformed other drug classes on sleep efficiency (defined as the amount of time spent sleeping relative to time in bed) and total sleep time. They demonstrated superior tolerability. One meta-analysis found that Dayvigo specifically had the most favourable profile of any agent examined.

Most importantly, DORAs consistently preserve or minimally alter sleep architecture, with little to no effect on slow-wave sleep and even improvements in REM sleep. This is not a minor distinction. During slow-wave sleep, the brain activates the glymphatic system, a specialized waste clearance mechanism in which neurons and glial cells shrink slightly, opening approximately 60% more interstitial space. This allows cerebrospinal fluid to circulate more freely, exchanging with interstitial fluid and carrying metabolic waste, including beta-amyloid and abnormal forms of tau, towards disposal pathways. Animal studies suggest that glymphatic clearance of beta-amyloid roughly doubles during sleep, particularly during deep non-REM sleep.

If a sleep medication suppresses slow-wave sleep, it may be interfering with the brain’s primary detoxification system. The architecture-preserving properties of DORAs are therefore not merely a comfort feature, they may have neuroprotective implications, particularly for patients at elevated risk of neurodegenerative disease. The potential of DORAs in Alzheimer’s prevention in high-risk populations is an area of active and warranted investigation.

The behavioural foundation: what must come first

None of this is to suggest that medications are the foundation of good sleep. They are not. The foundation is behavioural. It is the alignment of our lifestyles, environments and mental attitudes with the cues our biology requires.

For circadian alignment, this means regular wake times, meals and bedtimes; sunlight exposure as soon as possible after waking; reduced light and psychological stressors in the hours before bed; and a cool, dark bedroom. For sleep pressure, it means cultivating and conserving the homeostatic drive through exercise performed earlier in the day, avoiding sleeping in or napping and limiting caffeine to the morning hours.

For hyperarousal, the mechanism that sleep hygiene alone does not reliably fix, cognitive behavioural therapy for insomnia (CBT-I) should be the first-line treatment. CBT-I does not simply try to make the patient more tired. It targets hyperarousal directly, reducing cognitive and physiological activation and retraining the association between the bed and wakefulness. This is why it often succeeds where sleep hygiene fails.

If you are a person who remains fully awake after everyone else has gone to bed, or who wakes spontaneously well before dawn, or who suffers from jet lag, or who chronically stays up late on weekends only to find that your sleep poor during the work week, your problem likely lies in circadian misalignment. If your difficulty seems independent of schedule, but you are excessively sleepy during the day or wakeful at bedtime, especially if you nap or rely heavily on caffeine, your problem likely lies in inadequate or poorly consolidated sleep pressure.

A framework for the individual

When evaluating any sleep intervention, whether behavioural, psychological, or pharmacological, several questions are worth asking:

Which of the four mechanisms is primarily disrupted? Does the proposed intervention act on that mechanism? What does it do to sleep architecture? If it flattens the stages rather than supporting them, it is producing unconsciousness, not sleep. What is the risk profile for dependence, cognitive impairment, falls, complex behaviours or respiratory depression? And finally, is this intended as a bridge across an acute disruption or as a long-term solution?

Medications are tools, not foundations. They can be valuable when used deliberately, matched to the specific problem and ideally as a short-term bridge rather than a chronic crutch. For patients dealing with an acute crisis, chronic pain or deeply rooted anxiety, they can fill a gap that behavioural interventions alone cannot immediately close. But the key word is matched. Reaching for a drug without understanding the mechanism you are trying to correct is a recipe for tolerance, dependence, worsened sleep architecture or the all-too-common scenario of needing more to obtain less.

The deeper pattern

There is a broader lesson here that extends beyond sleep. We have engineered an environment that disrupts our biology at multiple levels simultaneously: light, temperature, social timing, dietary patterns, psychological stress and then we are surprised when the biological systems fail. Few organisms in their natural environment have trouble sleeping. It is a testament to the mismatch between the environment we have created and the biology we inherited.

An estimated 15% of the US population regularly takes some kind of sleep-aid drugs. Yet, our hunter-gatherer ancestors did not sleep dramatically more than we do. Their total sleep time was roughly comparable and some experienced more fragmented sleep. But they possessed extraordinarily strong circadian rhythms and almost no difficulty sleeping.

That is worth remembering the next time you reach for a sleeping pill.

It might surprise you to learn that buried deep inside our gut is a network of some 500 million neurons, called the Enteric Nervous System (ENS), and often referred to as our “Second Brain.”

One of the body’s most important neurotransmitters is called serotonin. It is the chemical that regulates our level of happiness, anxiety and mood, and up to 95% of our serotonin is produced in the gut.

Most of us give little thought to our gut health apart from when it is giving us obvious distress, but living deep in our large intestines is somewhere between 10 trillion and 100 trillion microorganisms that make up our gut microbiome.

The activities of our gut microbiome determine our energy levels, immunity and even our risk of dying from chronic disease.

The Forgotten Garden

We tend to treat our bodies like a collection of separate parts: the heart, the brain, the skin, etc. but the gut microbiome is the thread that stitches them all together.

Think of the gut not just as a digestion tube, but as a complex, living garden. We are the host. We provide shelter and food to our gut microorganisms and in return, they provide our body with essential services, such as:

1. Making certain vitamins (Biotin, Vitamin K and most B vitamins);

2. Breaking down toxins;

3. Training our immune system. Up to 80% of our immune cells live in the gut. The bacteria teach them which enemies to fight and which friends to ignore. Without this training, bad bacteria are permitted to thrive and good bacteria are attacked.

When colonies of bad bacteria are allowed to grow, it leads to gut dysbiosis. A disrupted gut microbiome is linked to many diseases, from Irritable Bowel Syndrome (IBS) and obesity to Parkinson’s disease, Alzheimer’s, anxiety and depression.

The Miracle Molecule You’ve Never Heard Of

One of the most important molecules that is produced in the gut is called butyrate.

Butyrate is a Short-Chain Fatty Acid (SCFA). Along with other SFCAs, it is produced when our good gut bacteria ferment dietary fibre. It is vital to our gut and overall health because:

• Butyrate is the primary energy source for the cells lining our colon (known as colonocytes). Without it, those cells starve, compromising the integrity of our gut barrier;

• Butyrate maintains tight junctions in our gut lining. A poor diet leads to those junctions open up, creating a “leaky gut” which allows toxins to enter the bloodstream, causing body-wide inflammation;

• Butyrate talks to our brain, through the Vagus nerve (Cranial Nerve X), the direct hotline from your gut to your brainstem.

The “Biotics” Cheat Sheet

No doubt most readers will be familiar with probiotics for promoting gut health, some will even have heard of prebiotics, but few will know about postbiotics. Here is the simple breakdown of what each one is:

• Prebiotics: The fertilizer. (Food for the good bugs). Found in: Garlic, onions, leeks, asparagus, bananas, oats;

• Probiotics: The live seeds. (The bacteria themselves). Found in: Live yoghurt, kefir, kimchi, kombucha, miso;

• Postbiotics: The harvest. (The beneficial metabolites, like Butyrate). Produced when probiotics eat prebiotics. This is the goal.

However, if you have no health issues, you do not need to take probiotic supplements. You are better off spending your money on real food.

The Longevity Connection

Why do centenarians (people over 100) live so long? It’s not just good genes.

Data shows that healthy centenarians have a much more diverse gut microbiome than typical 70-year-olds. They have youth-associated features in their guts. They have high levels of good bacteria like Bacteroides and low levels of pathogenic “weeds.”

In a study of 9,000 older adults, those with less diverse gut environments were nearly twice as likely to die as their peers with rich, diverse guts.

So whilst we can’t change our birth year, we can change the diversity of our gut garden through our diet.

How to Build a Healthy Gut

My top 5 tips for improving your gut health:

1. Eat the Rainbow. You need 30+ different plant types a week. Not just broccoli. Think fruits, nuts, seeds, legumes, herbs, spices. The diversity of the food creates the diversity of the bugs;

2. Stop Over-Sanitizing. Exposure to pets, playing outdoors and even friendly soil microbes help build a robust immune system. You don’t need to sterilize your life;

3. Fix Your Sleep. Chronic stress and poor sleep physically damage your gut microbiome. The gut-brain connection is a two-way street. If your brain is stressed, this is reflected in your gut;

4. Eat Fermented Foods. Try and consume at least one serving of fermented food every day. Examples of fermented food sources are live yoghurt (make sure the product description states “contains live bacteria” - most don’t), kimchi, natto, sauerkraut, kefir, miso, tempeh and pickles (but not those pickled in vinegar);

5. Ditch Ultra-Processed Foods. Also avoid emulsifiers and artificial sweeteners act like weed killer in your gut garden. They are often found in mayonnaise and pre-made salad dressings.

Since you started reading this article, your second brain has been hard at work, sending signals up your Vagus nerve, trying to regulate your mood and fight off inflammation.

If you want to lower your risk of CVD, Alzheimer’s, or just feel less anxious and have more energy, consider changing what’s on your plate. Are you feeding the good guys or are you letting the weeds take over?

Until next time, stay healthy from the inside out.

When talking to people about healthy ageing, there is a lot of confusion about what actually moves the needle. We all know about the likes of creatine and omega-3, but there is a specific compound most people have never heard of that might be one of the most important pieces of the longevity puzzle.

If you care about keeping your brain sharp and your body resilient as you get older, please read on. I hope this will convince you that there is a secret weapon hiding in your grocery store’s produce aisle.

There is a naturally occurring amino acid called ergothioneine that might make the difference between a long life and a long, healthy life.

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If you want to protect your brain and fight ageing at a cellular level - and given what I’ve written before about creatine, I hope you do - you need to know about the “longevity vitamin” that most doctors aren’t telling you about. Not a fad. Not a drug. A fundamental piece of human biology we are just beginning to understand.

Let me explain why this compound is so special and why you need to start including it in your diet.

The Mushroom Mystery

For decades, scientists have known about ergothioneine. It was discovered in 1909 in a fungus, but for the longest time, everyone ignored it. They assumed it was just another nice-to-have antioxidant, but nothing special.

Here’s where they were wrong.

In 2005, researchers discovered that the human body has a specific, dedicated transporter for ergothioneine . Think about that for a second. Your body doesn’t waste energy building specialized machinery to import a nutrient unless that nutrient is essential for survival. We have transporters for glucose, for amino acids and, as it turns out, for ergothioneine. The transporter is called OCTN1, and it actively pulls ergothioneine from your food into your cells, specifically targeting areas under the most stress: the liver, the bone marrow and, most importantly, the brain.

Nature doesn’t build a subway system to a ghost town. If your body is working this hard to get ergothioneine, it means it needs it to function.

The Brain Protection You Didn’t Know You Needed

So, what is it actually doing in your brain?

This is where the latest science gets exciting. Ergothioneine is a master antioxidant, but it operates differently to the vitamins you buy at the pharmacy because ergothioneine gets inside the cellular machinery.

Specifically, it accumulates in mitochondria, the tiny batteries inside your cells that generate energy. As we age, these batteries rust from the inside out, a process called oxidative stress. This rust is a primary driver of neurodegeneration, which is the physical loss of brain cells that leads to memory loss and cognitive decline.

Recent studies published in major journals (see links below) show that ergothioneine is a neuroprotective powerhouse. It doesn’t just stop the rust; it also reduces neuroinflammation (brain swelling) and supports the garbage disposal systems (currently believed to be via perivascular drainage) that clear out toxic proteins, namely amyloid-beta (Aβ) plaques . In short, it helps keep your brain clean and energized.

The Data Is Hard to Ignore

If the biochemistry isn’t enough for you, look at the human data. We aren’t just guessing about this stuff anymore.

Researchers have found that low blood levels of ergothioneine are a red flag for trouble ahead. One comprehensive review published in recent months noted that observational data consistently link low ergothioneine levels to cognitive impairment, frailty and even cardiovascular disease.

Specifically, studies on ageing populations show that individuals with higher levels of ergothioneine have lower rates of dementia and Parkinson’s disease. In animal models, supplementing with ergothioneine has been linked to a significant extension of healthspan.

The Exercise Connection (Bonus Points)

I wrote recently about how I love creatine for the brain. Interestingly, ergothioneine might work even better when you pair it with physical activity.

A recent short review in a major biochemistry journal proposed that ergothioneine and exercise are a “match made in (cognitive) heaven”. Why? Because exercise builds new blood vessels and neurons (neuroplasticity), while ergothioneine protects those new, fragile cells from burning out. One builds the engine, the other provides the coolant.

Why Isn’t Everyone Using This?

Three main reasons:

Firstly, it’s new. The discovery of the specific transporter is only 20 years old. Science moves slowly and dietary guidelines move even slower.

Secondly, food sources. You can’t get massive doses from a standard steak and potato diet. The richest source by far is mushrooms, specifically oyster, shiitake and porcini. Unless you are eating pounds of gourmet mushrooms daily, your levels might be suboptimal.

Thirdly, awareness. Most general practitioners are focused on treating disease, not optimizing cellular longevity. They won’t check your ergothioneine levels because, frankly, most don’t know to look.

What You Should Do

If you want to take advantage of this science, you don’t necessarily need expensive IV drips. The simplest approach is to eat more mushrooms. Add a handful to your omelette or scrambled eggs in the morning and slice a few in your salad, or just stir fry them and serve them as a side dish to your main course. They are delicious.

If you are looking for a more targeted approach, consider supplementation. Ergothioneine is stable, safe and has been approved as a food ingredient in Europe and the US . Because it isn’t a drug, quality can vary but the pure compound is widely available.

The Bottom Line

Ergothioneine isn’t a magic pill. It won’t undo decades of poor sleep and high stress. But the evidence is overwhelming that this “forgotten” nutrient plays a non-negotiable role in brain health and longevity.

We have a specific gene that reaches out and grabs this compound to protect our most vital organ. Don’t starve your body of the tools it needs to defend itself.

Eat your mushrooms and start giving your brain the edge it deserves.

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Want to dig a little deeper? Here are a few recent scientific publications about ergothioneine:

Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals

Ergothioneine for cognitive health, longevity and healthy ageing: where are we now?

Ergothioneine and exercise: A match made in (cognitive) heaven?

For quite a few years now, NAD+ has been marketed as one of the great longevity molecules. The pitch is seductive: boost your cellular energy, slow ageing, improve metabolism, sharpen your brain and maybe even buy yourself a little more healthy life. On paper, it sounds like the kind of intervention everyone should want.

But the more closely you look at the evidence, the more the story starts to fall apart.

The real issue is not whether NAD+ matters biologically. It does. The issue is whether taking expensive precursors like NR and NMN actually produces meaningful benefits in humans. And so far, the answer looks increasingly underwhelming.

The NAD+ Hype Machine

The longevity world has spent years arguing over which precursor is better: NR or NMN. Each camp has its believers, its influencers, and its studies. But this debate often misses the larger point. If both compounds are mostly converted by the body and gut bacteria into simpler vitamin B3 forms anyway, then the marketing narrative starts to look a lot less impressive.

That matters because people are not paying for cheap vitamin B3. They are paying premium prices for the promise of precision.

And precision is exactly what the data has struggled to deliver.

The Numbers Game

A lot of the excitement around NAD+ supplements comes from one very specific outcome: they can raise blood NAD+ levels. That sounds good. It is good, at least in the narrow sense that a biomarker moves in the desired direction.

But biomarkers are not the same thing as outcomes.

You can raise a lab value without improving strength, energy, cognition, metabolic health or how a person actually feels. And when you look at human trials, that is where the story becomes much less exciting. The increase in NAD+ often does not translate into measurable functional benefit.

The Gut Bacteria Problem

One of the more interesting parts of the NAD+ story is that oral precursors may not even behave the way people imagine. Instead of neatly entering the bloodstream and heading straight into cells, they can be metabolized along the way, including by gut bacteria.

In plain language: the supplement you think you are absorbing may not be arriving in the form you paid for.

That does not automatically mean the compounds are useless. But it does mean the story is messier than the supplement industry would like to admit. When a product relies on elegant mechanisms in a brochure but messy biology in the real world, the final result is usually more ordinary than advertised.

What Actually Moves the Needle

If the goal is youthful NAD+ biology, one of the strongest signals we have is not a capsule. It is exercise.

Movement improves mitochondrial function, metabolic flexibility, and cellular resilience in ways that are far more robust than the average supplement claim. In other words, the body seems much more interested in being challenged than in being spoon-fed a molecule.

That is the uncomfortable truth for the NAD+ industry: the most effective “NAD+ booster” may be the one that costs nothing and requires effort.

My Current View

If new evidence emerges that shows NAD+ supplementation does improve overall health and longevity, then I would be happy to change my mind, but the current science is telling us that:

• Raising NAD+ levels is not the same as improving health;

• NR and NMN may look impressive biochemically, but the functional payoff in humans remains weak;

• Exercise still beats most supplements when it comes to real-world mitochondrial health.

So if you want to spend money on NAD+ precursors, that is your choice. But do it with your eyes wide open. Do not confuse a biomarker change with a meaningful clinical effect.

The longevity world has a habit of turning complicated biochemistry into simple optimism. NAD+ is a perfect example of why that can be misleading.

If you want the most reliable way to support your cellular energy systems, start with the basics: move more, train consistently, sleep well and stop assuming every expensive molecule is a breakthrough.

What Is Psyllium Husk?

Psyllium husk is the outer coating of the Plantago ovata plant’s seeds, rich in soluble fibre that swells into a gel when mixed with water. This mucilaginous quality makes it a staple in natural remedies for bowel regularity.

It contains mostly arabinoxylans, a type of hemicellulose, providing up to 80% soluble fibre by weight, far higher than many grains or fruits.

Gut Health Powerhouse

Psyllium husk excels at relieving constipation by softening stools and promoting easier passage, while also firming loose stools to manage diarrhoea. Its gel formation increases stool water content and adds bulk, balancing irregular bowel habits.

Studies show it fosters a healthier gut microbiome by boosting beneficial bacteria like Faecalibacterium, which produce short-chain fatty acids such as butyrate to reduce inflammation and support Irritable Bowel Syndrome symptoms (5-10% of the world’s population suffers from IBS.)

Heart and Cholesterol Benefits

The fibre binds bile acids in the intestines, forcing the liver to use more cholesterol to produce new bile, thereby lowering LDL (”bad”) cholesterol without affecting HDL (”good”) levels. Regular intake can reduce total cholesterol by 5-10%.

This mechanism mirrors statin-like effects but naturally, offering cardiovascular protection backed by clinical evidence.

Blood Sugar Control

Psyllium husk also slows carbohydrate absorption, blunting post-meal glucose spikes and improving long-term glycaemic control, which is ideal for those with prediabetes or metabolic health issues. It forms a viscous barrier in the gut that delays sugar uptake. Human trials also confirm that it lowers fasting blood sugar, especially when taken before meals.

Weight Management Aid

By expanding in the stomach, psyllium husk promotes satiety, reducing calorie intake without hunger. It also stabilizes digestion during weight loss, countering common side effects like constipation from low-fibre diets.

Pair it with water 30 minutes before meals for best results; studies note modest but sustained weight loss support.

Dosage Tips

Try starting with 3-5g daily, springled over oats, yoghurt or mixed in 8-12 oz water or smoothies. You can add it to soups and sauces as a thickener too - it doesn’t taste of anything, at least nothing that I could taste. Increase to 2-3g per meal over time. Always mix it with plenty of water as it absorbs a lot of it, hence why it makes an excellent soup or sauce tickener.

With so many health benefits from this natural plant source, why not try incorporating it into your daily diet and see if you notice any of these health benefits?

What Is Astaxanthin?

Astaxanthin (pronounced as-ta-ZAN-thin) is a fat‑soluble carotenoid mostly produced by microalgae, particularly Haematococcus pluvialis. It then accumulates up the food chain in krill, shellfish and salmon, giving them their characteristic pink‑red hue. Unlike beta‑carotene, astaxanthin cannot be converted into vitamin A; its benefits are thought to arise from its direct antioxidant and anti‑inflammatory actions.

At the molecular level, astaxanthin is unusual. Its elongated structure allows it to span cell membranes, with one end protruding into the watery exterior and the other into the interior of the cell, while the middle anchors within the lipid bilayer. This “transmembrane” positioning means it can protect both the aqueous and fatty compartments of the cell from oxidative damage, and it appears to lodge particularly well in mitochondrial membranes. Since mitochondria are both the powerhouse and a major source of reactive oxygen species, this targeting is potentially important.

Oxidative Stress, Inflammation and the Biology of Ageing

To understand why astaxanthin is interesting, we need to revisit the central pillars of biological ageing. Many of the diseases of ageing, from atherosclerosis and type 2 diabetes to Alzheimer’s disease and sarcopenia, share three pathological features:

• Chronic oxidative stress (an excess of reactive oxygen species overwhelming the body’s antioxidant defences);

• Persistent, low‑grade inflammation (sometimes called “inflammageing”);

• Mitochondrial dysfunction (impaired energy production and defective quality control).

These processes feed into each other. Oxidative stress damages lipids, proteins and DNA, which triggers inflammatory pathways. Inflammatory cytokines (cell signalling proteins) in turn impair mitochondrial function, leading to more oxidative stress – a vicious cycle. Over decades, this slow burn contributes to endothelial dysfunction, insulin resistance, neurodegeneration and tissue fibrosis.

Astaxanthin is often described as a “multi‑target” molecule, because it appears to modulate all three of these pillars. It is a potent free radical scavenger, it can inhibit key inflammatory signalling pathways and it may help to preserve mitochondrial integrity and function. Whether these biochemical effects meaningfully translate into better health outcomes in humans is the key question.

Cardiovascular Health and Lipids

Cardiovascular disease is the leading cause of death globally, and its roots can be traced in large part to damage to the vascular endothelium and to the oxidation of LDL cholesterol. Oxidised LDL is particularly atherogenic (forms plaques on the arterial walls); it is more readily taken up by macrophages (a type of white blood cell, part of the immune system), which then turn into foam cells, a precursor to arterial plaque.

Astaxanthin’s ability to insert into lipoproteins and cell membranes has led to the hypothesis that it might protect LDL particles from oxidation and thus slow the atherosclerotic process. Small human trials have suggested that supplemental astaxanthin can:

• Reduce markers of lipid peroxidation;

• Modestly lower triglycerides and raise HDL in some individuals;

• Improve measures of arterial stiffness or endothelial function in certain settings.

However, these studies are typically short, small and heterogeneous in design. They show encouraging shifts in surrogate markers (such as oxidised LDL, inflammatory markers and arterial stiffness) but they do not yet demonstrate reductions in hard outcomes like myocardial infarction or stroke. In other words, astaxanthin may improve the underlying terrain, but we do not yet know whether that translates into fewer heart attacks.

Metabolic Syndrome and Insulin Resistance

Metabolic syndrome is one of the major upstream drivers of age‑related disease. Please read my article on this topic from December 2025 if you haven’t already. Insulin resistance, visceral adiposity, dyslipidaemia and elevated blood pressure quietly smoulder for years before announcing themselves with a heart attack, a cancer diagnosis or cognitive decline.

In animal models of diet‑induced obesity and diabetes, astaxanthin has been shown to:

• Improve insulin sensitivity;

• Reduce hepatic fat accumulation;

• Lower fasting glucose and improve lipid profiles; and

• Decrease inflammatory markers within adipose tissue.

The mechanisms proposed include reduced oxidative stress in pancreatic beta cells, improved mitochondrial function in skeletal muscle and liver and dampening of inflammatory signalling in adipose tissue. All of these would be favourable in the context of metabolic syndrome.

Human data is less robust but point in a similar direction. Small trials in people with obesity, insulin resistance or prediabetes have reported modest improvements in oxidative stress markers, some lipid parameters and, in a few cases, insulin sensitivity indices.

Brain & Skin Health, Vision and Neuroprotection

The brain is exquisitely sensitive to oxidative stress. It is rich in lipids, consumes a disproportionate amount of oxygen and has relatively limited antioxidant reserves. Neurodegenerative diseases such as Alzheimer’s and Parkinson’s have clear oxidative and inflammatory components, alongside misfolded proteins and synaptic dysfunction.

Astaxanthin is one of the few carotenoids that can cross the blood–brain barrier. Once there, it appears to concentrate in neuronal membranes and mitochondria. Preclinical studies suggest that it can:

• Reduce oxidative damage in brain tissue;

• Inhibit neuroinflammatory pathways; and

• Protect neurons from amyloid‑beta or glutamate‑induced toxicity.

Clinically, there is early evidence that suggests astaxanthin may improve measures of cognitive fatigue, reaction time and mental clarity in small human studies, particularly in middle‑aged or older adults with high oxidative stress. These findings are interesting but preliminary. They hint at a possible role in maintaining cognitive function and perhaps slowing the trajectory towards neurodegeneration, but they fall well short of proving disease‑modifying effects in Alzheimer’s or other dementias.

The eye is another organ that is susceptible to oxidative stress, particularly in age‑related macular degeneration (AMD). Astaxanthin accumulates in retinal tissues and is often combined with other carotenoids such as lutein and zeaxanthin (these are also must-take supplements for eye health) aimed at supporting macular health.

Astaxanthin also has protective effects on the skin: a systematic review and meta-analysis published in 2021 looked into the effects of astaxanthin on skin ageing and found that it significantly restored moisture content and improved elasticity.

Muscle, Recovery and Exercise Performance

Skeletal muscle is our metabolic sink for glucose and a key determinant of healthy ageing. Unfortunately, it is also vulnerable to mitochondrial dysfunction and oxidative damage, which can contribute to sarcopenia and frailty.

Because astaxanthin lodges in mitochondrial membranes, it has been investigated for its potential role in muscle performance and recovery. Some human studies in athletes and recreationally active individuals have shown:

• Reduced markers of exercise‑induced oxidative stress;

• Slight improvements in endurance or time to exhaustion in certain protocols; and

• Reduced muscle damage markers and subjective soreness after strenuous exercise.

These effects, if real and reproducible, could be relevant not only to athletes but also to older adults trying to build or maintain muscle mass. Anything that enhances mitochondrial function and lessens oxidative damage during and after exercise could make physical activity more sustainable, especially in those already on the cusp of sarcopenia.

Dosing, Safety and Sources

Astaxanthin supplements are typically derived from microalgae and the doses range from 2 mg to 24 mg per day, with most human studies clustering around 4–12 mg daily. At these doses, astaxanthin appears to be well tolerated, with few reported adverse effects beyond occasional gastrointestinal discomfort or a harmless, slight orange tint to the skin with long‑term high intake. I take 12 mg after breakfast every day.

You can also find astaxanthin in dietary sources such as:

• Wild salmon (especially sockeye), trout and shrimp;

• Krill and krill oil supplements;

• Farmed salmon may contain synthetic astaxanthin; wild fish obtain it from algae via the food chain.

However, the amounts used in clinical studies are usually higher than can be reliably obtained from diet alone, which is why most of the research focuses on supplemental forms.

Astaxanthin is not a magic bullet

Astaxanthin will not compensate for a sedentary lifestyle, a diet of ultra‑processed foods or chronic sleep deprivation. The key upstream drivers of ageing, namely metabolic syndrome, insulin resistance, physical inactivity and chronic stress must still be addressed through lifestyle and, where appropriate, medications.

However, astaxanthin is an intriguing candidate as an adjunctive strategy to maintaining good health. Its positioning in cell and mitochondrial membranes, its broad antioxidant and anti‑inflammatory actions, and its ability to reach vulnerable tissues such as the brain, retina and vascular endothelium make it a plausible tool to gently nudge biology in a more favourable direction.

In other words, astaxanthin currently sits in the space of a potentially useful, low‑risk supplement that might support healthy ageing when layered on top of a solid foundation of lifestyle interventions.

I have noticed in recent months when talking to people about creatine, that there are still some of you out there on the fence. If you are one of these people, please read my article on creatine, which I hope will convince you that there is only upside to taking this supplement, especially as we get older.

Some people have told me they stopped taking creatine after their last medical because their results came back with elevated creatinine levels, which doctors use as a measure of kidney function. For clarification, creatine is the name of the supplement, and creatinine is the metabolic waste product from breaking down creatine, which the kidneys filter out from the blood.

If you’re taking creatine - and given what I’ve written before, I hope you are - you need to know something important about how doctors check your kidney function. The standard blood test most doctors order can give false results in people who supplement with creatine. Not slightly off. Meaningfully wrong. Enough to trigger unnecessary worry, referrals to kidney specialists, and in some cases, people stopping a supplement that was never harming them.

Let me explain why this happens and what you can do about it.

The Creatinine Problem

When you go for a routine blood test, your doctor typically measures something called creatinine to assess your kidney function. This has been standard medical practice for decades. As I mentioned earlier, creatinine is a waste product your muscles produce, and healthy kidneys filter it out efficiently. If creatinine levels rise, doctors assume your kidneys aren’t working properly.

Here’s the issue: creatinine is not a neutral marker. Your body produces more of it when you take creatine supplements. This is not controversial or disputed. It’s basic biochemistry. Creatine breaks down into creatinine. More creatine in your system means more creatinine in your blood, regardless of whether your kidneys are functioning perfectly.

So you can have healthy kidneys, take a safe and beneficial supplement, and still show “abnormal” kidney function on a standard blood test. I’ve seen this happen to friends. Their doctors panic. They panic, and they stop taking creatine.

Why Your Kidney Test Might Be Lying to You (If You Take Creatine)

Enter Cystatin C

There is a better test. It’s called cystatin C, and it measures kidney function without the creatine interference problem.

Cystatin C is a protein produced by all the cells in your body at a constant rate. Unlike creatinine, its production doesn’t change with muscle mass, diet or creatine supplementation. Your kidneys filter it. If your kidneys work well, cystatin C stays low. If kidney function declines, cystatin C rises. Simple. Accurate. No false alarms from your supplement routine.

Why Isn’t Everyone Using This?

Three main reasons:

First, habit. Creatinine has been the standard for so long that many doctors order it automatically without thinking about the patient’s context. They see “kidney function test” and check the creatinine box.

Second, cost. Cystatin C costs more to measure. Not dramatically more, but enough that laboratories and healthcare systems resist switching over entirely.

Third, awareness. Many physicians simply don’t know that creatine affects creatinine results. This is particularly true for general practitioners who may not see many patients who supplement regularly.

What You Should Do

If you take creatine and you’re getting blood work done, you have options.

The simplest approach: ask your doctor to add cystatin C to your panel. Any doctor can order this. It’s a standard test available at major laboratories. You don’t need a specialist.

If your creatinine comes back slightly elevated and you know you take creatine, don’t worry. Ask whether cystatin C was measured. If it wasn’t, request it before accepting any diagnosis of kidney impairment.

For those who want the most accurate picture, there’s a combined equation that uses both creatinine and cystatin C. This is now recommended by major kidney organizations when results seem inconsistent with how you actually feel.

Still A Safe Supplement

Creatine is one of the safest, most effective supplements you can take. The evidence for its benefits - physical and cognitive - is overwhelming. But the way we monitor kidney function hasn’t caught up with how many people now use this supplement.

Cystatin C isn’t exotic or experimental. It’s a validated, widely available test that simply works better for people who train, who have higher muscle mass, or who take creatine.

Don’t let an outdated blood test convince you to abandon something that improves your health. Know the difference. And keep taking your creatine.

It is important to stress that these life expectancies are mean averages, which can be a little misleading because one is inclined to conclude that everyone died young, at least by today’s measure of age. However, the primary reasons behind the low average life expectancy were a high mortality rate during childbirth (for both the baby and the mother), as well as a high rate of infant mortality (under 5s). Medical knowledge was not sophisticated enough to deal with childbirth complications, and this was accompanied by poor sanitation and low hygiene standards, which led to many preventable deaths by today’s standards. We also didn’t have vaccines to protect young children from life-threatening diseases, nor did we have antibiotics to treat bacterial infections. So broadly speaking, if a child was lucky enough to survive birth and make it to the age of 5, then life expectancy increased significantly, although war, famine and natural disasters remained a constant threat in many parts of the world. These were different times and life was seldom taken for granted.

Figure 1: Average Human Life Expectancy Since 1770

Drivers of Increased Life Expectancy

After flatlining for centuries, life expectancy began to increase as a result of a series of scientific breakthroughs.

In 1796, there was a true medical breakthrough – Edward Jenner, a doctor from England – developed the world’s first vaccine against smallpox. It proved very effective against this deadly disease that is believed to have been around for as long as 3,000 years. It is estimated to have claimed the lives of around 500 million people, 300 million of them in the twentieth century alone, making it one of the deadliest infectious diseases in human history. Smallpox is no longer a health threat thanks to Edward Jenner and in 1980, The World Health Organization (WHO) declared it officially eradicated.

After Jenner, in the mid-to-late nineteenth century, came Louis Pasteur from France. He was a pioneer in germ theory and Pasteurisation to kill harmful microbes. He emphasized the importance of sterilisation and aseptic techniques to prevent contamination and infection. He also developed vaccines for rabies, anthrax and fowl cholera. At around about the same time, there was a German physician and microbiologist by the name of Robert Koch. He is considered to be one of the founders of modern bacteriology and established the scientific discipline of microbiology.

It would be remiss not to mention another physician and microbiologist who also made a major contribution to increasing human life expectancy – Alexander Fleming, the Scot who discovered the first antibiotic, Penicillin, in 1928. This undoubtedly saved millions of lives during World War Two, treating infections, and it continues to do so today along with many other antibiotics.

There were of course many additional advances in medicine that continued to contribute to increasing average life expectancy. Initially, these were often developed in western countries, but later they were adopted by the rest of the world. Such advances include the advent of anaesthesia, the use of antiseptic techniques to sterilize surgical instruments, blood transfusions, organ transplants, imaging technology, randomized clinical trials, the discovery of the structure of DNA and thousands of small molecule drugs and biologics that treat or prevent countless diseases, including cancers.

Today, average life expectancy globally at birth has climbed to around 73 years, according to the WHO, but this is much higher in more developed places. In 2025, Hong Kong women ranked number one in the world, with an average life expectancy of 88.39 years. The longest-lived men are also in Hong Kong, with a life expectancy of 83.10 years, making the average for both sexes 85.77 years (Table 1). Japan sits in second place with 85.00 years and South Korea in third with 84.53. It is interesting to note that in the life expectancy rankings globally, the top three places are all in Asia.

Table 1: Life Expectancy at Birth Across Asia-Pacific. Source Data: Statista

Demographic Challenges in Asia-Pacific

The Asia-Pacific region is undergoing an unprecedented demographic transformation, with the population of older persons projected to nearly triple by 2050, reaching approximately 1.3 billion people. This rapid ageing, driven by longer life expectancy and declining birth rates, positions Asia-Pacific at the forefront of one of the most significant global demographic trends. By mid-century, one in four individuals in the region will be aged 60 or older, profoundly impacting economic growth, healthcare systems, social protection frameworks and workforce dynamics.

While increased life expectancy marks a remarkable achievement in social and technological development, it also presents complex challenges such as income insecurity, healthcare accessibility and social inclusion, especially among vulnerable groups like older women. This article explores the multifaceted implications of ageing in the Asia-Pacific region, examines strategies to promote healthy longevity and highlights policy innovations essential for sustainable, inclusive growth and well-being in an ageing society.

Leading Causes of Death

Without a doubt, modern medicine has been able to keep us alive for longer. At the turn of the twentieth century, life expectancy globally was only 32 years. Just one hundred years later, that figure had increased to 67 years, and as mentioned earlier, it is now up to 73 years, after a small dip during the Covid-19 pandemic, which disproportionately affected the elderly.

As a consequence of living a longer life, there is an increase in the number of age-related diseases, known as the disease of ageing. Every day, there are around 170,000 deaths around the world on average. Of these, it is estimated that 70-80% are attributable to the diseases of ageing, depending on the country/region.

The following are generally considered to be diseases of ageing:

• Cardiovascular disease (CVD)

• Cancer, with the deadliest being lung cancer, accounting for just under 20% of all cancer deaths worldwide

• Type 2 Diabetes (T2D)

• Respiratory diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and lower respiratory infections, such as pneumonia

• Neurodegenerative diseases, around two-thirds of which are Alzheimer’s disease

• Musculoskeletal disorders including osteoporosis, osteoarthritis and sarcopenia

• Age-related macular degeneration (AMD)

• Chronic kidney disease (CKD)

• Liver cirrhosis and fatty liver disease

Of these diseases, the top five, the so-called The Deadly Quintet, are responsible for the most deaths. These are: CVD, cancer, respiratory diseases, T2D and neurodegenerative diseases. An estimated 80% of all deaths of over 50s are associated with one or more of the Deadly Quintet.

Leading Causes of Death in Asia-Pacific

Asia-Pacific countries exhibit distinctive cancer patterns compared to global averages. Lung, liver and stomach cancers are much more prevalent and cause higher mortality in the region than in much of the West, where prostate, breast and colorectal cancers dominate.

The advanced Asian regions have a life expectancy more than 80 years and cancer as the leading cause of death. There have been many advances in modern medicine in methods to treat CVD and many cancers. However, as we move towards a super-aged society (defined as one in which at least 20% of the population is older than 65), more effort should be made on preventing these diseases from developing in the first place.

After type 2 diabetes, the most prevalent metabolic health issue in the Asia-Pacific region is Metabolic Syndrome (MetS), which comprises a cluster of risk factors including central obesity, dyslipidaemia (high triglycerides/low HDL), hypertension and impaired glucose metabolism.

Table 2: Estimated Number of Annual Deaths Globally (in millions) from The Deadly Quintet of Diseases

Leading Causes of Death by Country

Mainland China, Hong Kong, Taiwan and Macau

Mainland China: CVD, followed by cancer

Hong Kong: Cancer (about 25% of all deaths), CVD & pneumonia (another 25%)

Taiwan: Cancer (highest contributors being lung, liver and colorectal)

Macau: Cancer, followed by CVD

Japan

Cancer, followed by CVD

South Korea

Cancer (30% of all deaths), followed by CVD

Singapore

Cancer (about 25% of all deaths), pneumonia, CVD

The Diseases of Ageing

Without a doubt, modern medicine has been able to keep us alive for longer. At the turn of the twentieth century, life expectancy at birth globally was only 32 years. Just one hundred years later, that figure had risen to 67 years, and today it is higher still at 73 years, after a small dip during the Covid-19 pandemic, which disproportionately affected the elderly. In Hong Kong, the place I call home, life expectancy at birth is 85.77 years, the highest in the world, narrowly beating out Japan and South Korea. By sex, this breaks down to 83.10 years for men and 88.39 years for women.

As a consequence of living longer lives, there is an increase in the number of age-related diseases, aptly referred to as the disease of ageing. Every day, there are around 170,000 deaths around the world on average. Of these, it is estimated that 70-80% are attributable to the diseases of ageing, depending on the country/region.

By diseases of ageing, I am referring to the following:

• Cardiovascular disease;

• Cancer, with the deadliest being lung cancer, accounting for just under 20% of all cancer deaths worldwide;

• Insulin resistance and type 2 diabetes;

• Respiratory diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and lower respiratory infections, such as pneumonia;

• Neurodegenerative diseases, around two-thirds of which are Alzheimer’s disease;

• Musculoskeletal disorders, including osteoporosis, osteoarthritis and sarcopenia;

• Age-related macular degeneration (AMD);

• Chronic kidney disease (CKD);

• Liver cirrhosis and fatty liver disease.

Of these diseases, I call the top five The Deadly Quintet, which are responsible for the most deaths. In fact, an estimated 80% of all deaths of over 50s are associated with one or more of The Deadly Quintet. In a world with a rapidly ageing population, The Deadly Quintet is especially pertinent.

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The Role of Metabolic Syndrome

The diseases of ageing often take many years to develop. Sometimes the body gives early warning signs; other times the warning signs are too late, such as the case with a myocardial infarction (a heart attack). A heart attack is usually very sudden, with no prior warning to the sufferer that he has cardiovascular disease, more specifically atherosclerosis. If the person is fortunate enough to survive the event, it can serve as a wake-up call to take action to prevent the disease from progressing (by taking medication and adopting healthier lifestyle habits), but by then, the damage to the heart muscle has already been done.

However, cardiovascular disease takes many years to develop, similarly for the other four diseases of The Deadly Quintet. In many cases, the precursor to these diseases is a broader condition known as Metabolic Syndrome. In very general terms, this condition develops when the body starts to have problems regulating itself. Although there are cases of metabolic syndrome that are genetic, it is almost always a lifestyle disease, meaning that we can do something to prevent it.

Metabolic syndrome is a silent disease because it progresses very slowly over many years, initially with no symptoms. It describes a cluster of interrelated cardiometabolic conditions that, if left unchecked, will progress to cardiovascular disease, type 2 diabetes, neurodegenerative diseases and even some cancers.

One of the key signs of metabolic syndrome is insulin resistance. Insulin is an important signalling hormone for which every cell in the body has a receptor. Insulin’s most famous action is controlling blood glucose levels, whereby the insulin receptor allows glucose to exit from the blood and enter into the cells, where it is stored in the form of glycogen.

Unfortunately, there is no easy way to accurately measure insulin levels in the body outside laboratory conditions. Most common techniques measure blood glucose levels as a proxy, but that is not the same thing. Insulin levels can remain high in the body, even after blood glucose levels fall.

There is a more accessible test for measuring insulin resistance called HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). This test estimates insulin resistance using a simple blood test based on fasting levels of both plasma glucose and insulin.

Another way to determine whether a person likely has metabolic syndrome is to see if at least 3 of the following 5 conditions are met:

1. Increased waist circumference - over 94cm (37in) for men and over 80cm (31.5in) for women;

2. Elevated serum triglycerides (>150 mg/dL);

3. Reduced high-density lipoprotein (HDL) cholesterol (<40 mg/dL in men and <50 mg/dL in women) or currently taking medication for dyslipidaemia;

4. Elevated blood pressure (>130/85 mm Hg); and

5. Elevated fasting serum glucose (>100 mg/dL) or currently taking glucose-lowering medication.

Treating metabolic syndrome can be considered as an upstream intervention to prevent the development of The Deadly Quintet. It is one of the most overlooked low-hanging fruit, as it is treatable with some basic lifestyle interventions, and would significantly improve healthspans across populations. Treating insulin resistance will in many cases also treat metabolic syndrome.

What is Insulin Resistance?

Insulin resistance develops because too much glucose enters the bloodstream without anywhere for it to go. In a healthy person, carbohydrates from a meal are converted into glucose and released into the bloodstream. In response, the body releases insulin, which acts like a key, unlocking the skeletal muscle cells to allow them to absorb the glucose in the form of glycogen. Muscle cells account for over 80% of the post-prandial glucose uptake. Once the skeletal muscle cells are saturated with glycogen, excess glucose is diverted to the liver where it is stored, also as glycogen.

Insulin resistance starts to develop when both the skeletal muscles and the liver are already saturated with glycogen and additional glucose enters the bloodstream post-prandially. There is nowhere for this glucose to go, and if it stays in the blood for too long, it causes serious harm to nearly every organ system, especially blood vessels, nerves, kidneys, eyes and brain. So, in an effort to clear the glucose from the bloodstream, the body releases more insulin to increase the signalling, and the body reacts by freeing up storage space in the liver. It does this by converting the stored liver glycogen into fat through a process called de novo lipogenesis.

Simple Tips for Avoiding / Reversing Metabolic Syndrome

Metabolic syndrome is one of the fastest-growing diseases globally and is particularly linked to sedentary lifestyles and to eating ultra-processed, energy-dense foods.

The best way to avoid metabolic syndrome, or even reverse it, is to adopt these five lifestyle habits:

1. Be physically active - we are physical beings that evolved to always be on the move, which is why our bodies are struggling to cope with the modern, sedentary lifestyle in which we spend hours on end seated, staring at screens;

2. Consume no more calories than you burn in a day;

3. Build muscle - skeletal muscle acts like a sponge for glucose; the more skeletal muscle you have, the more glucose you can absorb from the bloodstream;

4. Incorporate plenty of fibre into your diet, consuming it at the start of a meal buffers the release of glucose into the bloodstream;

5. Take a 15-minute walk after a meal - this helps bring down both insulin and glucose levels post-prandially.

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Cardiovascular Disease Risk

It may come as a shock to some readers to discover that one third of all deaths worldwide are attributed to cardiovascular disease (CVD). It remains the leading cause of death by far, despite all the advances in medicine in recent decades. The World Health Organization estimates CVD deaths to be 21 million annually, which tran…

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Omega-3 fatty acids are crucial for maintaining overall health and well-being. These essential nutrients play a vital role in various bodily functions, including reducing inflammation, supporting heart health and promoting healthy ageing. Recent studies have highlighted the significant impact of omega-3s on longevity, muscle health, and mental well-bein…

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Creatine is for Everyone

I’ve been planning to write an article on creatine for some time now as it is a highly misunderstood supplement across the general population. In speaking with various friends and colleagues about creatine, there seems to be a misperception that (a) it’s only for body builders; and (b) it’s some kind of performance-enhancing drug, neither of which is correct.

So let me stress from the outset that creatine is a naturally occurring substance with undeniable health benefits for everyone, especially those 40 years and older.

I will explain why I believe creatine is one of the most beneficial supplements to take for men and women, not only because it supports our physical health but it has also been found to improve our brain function, something that becomes more important as we age. There is only one scenario I can think of in which taking creatine would be a disadvantage, and I will cover that at the end.

What is Creatine and Where Does it Come From?

Let’s start with the basics. There are three sources of creatine: our bodies make creatine endogenously, typically 1 to 2 grams every day. It is made in the liver, kidneys and pancreas, and synthesized from three amino acids (amino acids are the building blocks of life; they can be thought of as tiny Lego bricks, and the human body needs 20 different types to function. Proteins are made of chains of amino acids).

The three amino acids used to make creatine are arginine, glycine and methionine. Approximately 95% of our creatine is stored in our muscles and used for energy during high intensity activities. The remaining 5% is found in the brain, kidneys and liver.

Creatine is also found in some of the foods we eat - red meat, poultry and fish are great sources of creatine. To give you some idea of the creatine content, an 8-ounce steak (around 227 grams) contains around 2 grams of creatine.

Finally, creatine can be taken as a dietary supplement, usually in powder form. It is easy to find and relatively cheap to buy. Although there are various compounds of creatine (such creatine citrate, creatine hydrochloride and creatine phosphate), creatine monohydrate is the most widely studied and the cheapest version. It is a tasteless, odorless white powder that can be stirred into a liquid and drunk. The powder doesn’t dissolve very easily, especially in cold liquids, and can feel a little gritty on the teeth, but creatine monohydrate is also sold in a micronized form, which dissolves more readily in liquids and is slightly better absorbed by the body. It is the form I usually take.

Creatine supplementation has been studied extensively for decades and no health risks have been reported.

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The Benefits of Creatine Supplementation

The International Society of Sports Nutrition (ISSN) states that creatine is the most effective nutritional supplement currently available in terms of increasing high intensity exercise capacity and lean body mass during training. It also helps with muscle recovery after exercise.

For the less physically active readers, you will be interested to learn that there is increasing evidence to suggest creatine enhances memory, executive function and cognitive performance in healthy individuals, especially older adults. Creatine is essential for maintaining the brain’s energy levels and may even have neuroprotective properties.

As most of us will know first hand, sleep deprivation reduces cognitive function. A study published in Nature this year found that creatine supplementation can reverse some of the cognitive impairment induced by sleep deprivation.

Simply put, creatine is the number one supplement for improving our overall physical and brain health. It is the lowest hanging fruit of all supplements.

How Much Creatine To Take?

The most commonly recommended dose of creatine is a teaspoonful, or 5 grams per day.

People on a vegetarian or vegan diet will be missing creatine from food sources, so will benefit the most from creatine supplementation.

In rare cases, some people report gastro-intestinal (GI) issues after taking creatine, but they tended to be in cases where high doses were taken (20 grams per day or higher). I have always taken creatine with food and have never experienced any GI problems.

One of the effects of creatine is to pull more water into muscle tissue. Muscle is already 70% water, but creatine increases the water content further. This is beneficial when exercising as a more hydrated muscle is a stronger one, and a well-hydrated muscle is also less likely to cramp or become injured.

You will weigh more when you are taking creatine, but this extra weight is just water and not fat, so don’t be alarmed by this weight gain. In fact, creatine is more likely to result in a reduction in body fat as your resting metabolic rate will increase with the muscle growth which means your body will burn more energy. I find that I am around 1 to 1.5 kg (around 3 pounds) heavier when taking creatine daily. You will lose this extra water weight in usually 4 to 5 days after you stop taking creatine.

The extra weight gain can be a negative for a small percentage of the population: if you are a serious athlete where it is advantageous to be lighter, for example, a marathon runner or a cyclist. In such cases, the athlete can train on creatine for the added muscle conditioning and then come off creatine a week or so leading up to the race for the water weight loss.

So regardless of your fitness level or how often you go to the gym, give creatine a try and start to enjoy its many health benefits.

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This article provides an overview of what many sports scientists and longevity experts consider to be the most important indicator of overall health - VO2 max.

Let’s start with first explaining what VO2 max is. Put simply, it is your body’s capacity for processing oxygen. The V stands for volume, the O2 for oxygen and no prizes for figuring out that max …

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• Go to Bed and Wake Up at the Same Time Every Day: Try not to stray by more than an hour either way, even on weekends. Sleep loves regularity.

2. Maintain a Sleep-Inducing Environment

• Keep Your Bedroom Cool: Studies show that 18°C or 65°F is the optimal temperature for most people.

• Remove All Light From Your Ro…

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Health and longevity goes mainstream

For as long as I can remember, I have always been interested in staying fit and healthy. But my understanding of what that entails has changed dramatically over the years. Since my book on human longevity, called Juvenescence, was first published in 2017, there has been an explosion of information from scientists and …

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