Longevity - increasing healthy lifespan

Measuring biological age through epigenetic change

Epigenetic change occurs when chemical ‘tags’ are placed on parts of your DNA – which alters the way those genes function. In other words, the tags activate ‘good’ – or deactivate ‘bad’ – genes. A bit like a biological dimmer switch.

These epigenetic changes are driven by changes in your lifestyle – by diet, nutrient intake, exercise, stress, even the ambient temperature.

As part of my research into writing the book Delay Ageing: Healthy to 100, I took an epigenetic test. It confirmed I was considerably younger than my chronological age. Moreover, my biological brain age was so much younger than my chronological brain age that I could be up there at number 11 on their leaderboard.

But I’m certainly not going to enter this very questionable competition for 4 reasons.

Why I won't be signing up to this 'extreme sport'

A. The competitors are largely male, and I sense a lot of testosterone-fuelled rivalry.

B. Secondly, many are multi-millionaires and even billionaires, who spend small fortunes every year on high tech procedures and supplements. They aim to increase their lifespan – living to 120 - 150.

That seems a very elitist aim. Although no-one wants to die, imagine what would happen to the economy, pensions, housing and healthcare if we all attempted to add 40 or even 70 years to the average lifespan?

Whereas extending health span is desirable for both the individual and for society. This has always been our focus at Uni-Vite. Imagine the saving to the NHS if we extended the years in which people stayed healthy and free of diseases.

C. Thirdly, where is the enjoyment? The joie de vivre? Some of the extremists confine their meals to within just 4 hours a day. Or fast for 2 days a week. Or take 150 tablets daily (drug and nutrient interactions would surely be a big risk!). Or read their newspaper upside down in a mirror to boost their brain power. Or even, in one case, inject ‘rejuvenating’ blood transfusions from his son!

D. But the fourth reason is the most important. We already know how to hugely extend health span.

Health span extension via diet is already here

Ageing involves multiple pathways – the ‘Hallmarks of Ageing’ that I describe in my book Delay Ageing.

So the basis of health span – and lifespan – is a healthy diet with multiple nutrients counteracting those ageing pathways and supporting the body’s repair mechanisms, especially DNA repair.

That diet is one that essentially combines the best of the Mediterranean and Japanese diets, because decades of research prove they are the best ways of eating for health span.

The Delay Ageing Healthy Eating Plan

This is exactly what our Delay Ageing food plan does. A six-year study by the Centers for Disease Control and Prevention confirms that this way of eating – together with 21 minutes a day of moderate exercise that makes you slightly breathless (and not smoking) – can add no less than 18 years to your active life. Healthy Eating Plan | NutriShield

You can do even better, by reducing stress. Try our simple short stress reduction sequence.

So far, no high-tech or shiny new expensive procedures!

The role of health food supplements as you get older

The huge new body of ageing research IS indeed revealing more and more of the underlying causes of ageing.

The ageing issues that supplements can address:

♦ Your immune system becomes less effective.

♦ Cellular damage accumulates, but your ability to repair that damage (including damage to brain cells) lessens.

♦ Inflammation in cells increases – which is directly linked to multiple age-related illnesses.

♦ You need to clear out ‘senescent’ cells – defunct cells that have stopped dividing and should have been cleared by your immune system but have not. These accumulate over time – and linger on in your body, releasing toxins and causing inflammation. The vital task of clearing out these senescent cells is called autophagy (pronounced or-tof-agy).

♦ Your mitochondria accumulate damage and as you age, they create less energy from food. The problem is that you actually need more energy to power every function, including the increased demand on your immune system and for DNA repair.

So, you need to reduce mitochondrial damage and simultaneously support the ability of your mitochondria to create energy. Without this specific support, mitochondrial damage gradually increases – which manifests as tiredness, reduced DNA repair, cognitive decline, age-related illnesses and ageing itself.

There are plant nutrients that help protect your mitochondria from damage – especially polyphenols in fruits and vegetables. And you can counteract energy decline by supporting the production of an essential compound your body produces called NAD+. Increasing NAD+ levels in your cells then boosts the production of a group of proteins called sirtuins, and sirtuins support DNA repair. [Ref: The sirtuin family in health and disease | Signal Transduction and Targeted Therapy (nature.com)]

Supplements can help optimise your nutrient intake

While a really good preventative healthy diet like the Delay Ageing Healthy Eating Plan | NutriShield is an ideal basis, optimising that diet can bring you extraordinary results.

That’s why we designed NutriShield – a supplement that increases and optimises your intake of the 43 most protective nutrients identified in the Mediterranean and Japanese diets.

It helps you counteract each one of the interlinked causes of ageing – and therefore later-life diseases.

NutriShield also has nutrients that specifically support eye health, heart health, cognitive function and collagen production.

Physical activity aka 'exercise' is fundamental

To the nutritional baseline, you must commit to a minimum level of activity that maintains your core strength and aerobic fitness. The secret is to exercise 3-4 times a week, so you are slightly breathless.

Maintaining activity and exercise as you get older is fundamental to extending your health span. The very latest evidence shows that exercise increases a hormone called irisin, which helps clear the plaques and tangles that characterise Alzheimer’s patients. Exercise is medicine for the brain! [Ref. Alzheimer's: Exercise-induced hormone may help reduce plaque (medicalnewstoday.com)].

The Delay Ageing food plan plus a comprehensive health supplement and regular exercise is a common-sense approach that nevertheless takes into account the latest research the longevity ‘bio-hackers’ are basing their regimes on.

11 EASY FOOD WINS – simple daily tweaks

Before we look at the sort of supplements the bio-hackers are using – and how you can get many from your diet – I want to highlight just 11 really simple lifestyle actions. A huge amount of peer-reviewed research confirms they have unquestioned health span benefits.

Most of them are already included in the Delay Ageing Food Plan Healthy Eating Plan | NutriShield, but I have highlighted them here to show how easy they are to incorporate into your lifestyle.

♥ A HANDFUL OF NUTS each day – ideally walnuts and cashews.

♥ One serving of PEAS, BEANS, LENTILS OR HUMMOUS a day. The aim is to increase your fibre intake to 30g a day, which has a huge, positive impact on your microbiome.

♥ One serving a day of BERRY FRUITS – especially blueberries, bilberries, blackcurrants, redcurrants, raspberries, cranberries and strawberries. (Can also be included in a smoothie.) Fresh, frozen, canned, dried all count.

♥ One serving of GREEN LEAFY (cruciferous) VEGETABLES a day – cabbage, broccoli, spinach, kale, chard, Brussels sprouts. (Can also be included in soup or smoothie.)

♥ At least two more servings a day of COLOURFUL FRUITS and VEGETABLES. Consciously combine red, green, blue/purple and yellow/orange plant foods.

♥ MUSHROOMS 5 times a week.

♥ SWITCH as much as you can TO PLANT PROTEIN. That reduces your intake of methionine – an amino acid that is strongly linked to ageing and age-related illnesses. [Ref. Molecular mechanisms of dietary restriction promoting health and longevity | Nature Reviews Molecular Cell Biology] [Ref. Methionine-Restricted Diet: A Feasible Strategy Against Chronic or Aging-Related Diseases - PubMed (nih.gov)] [Ref. Methionine Restriction and Life-Span Extension - PubMed (nih.gov)]

♥ Cook as frequently as possible with GARLIC and EXTRA VIRGIN OLIVE OIL. They can significantly improve artery function and help lower blood pressure – especially in combination.

♥ Include FERMENTED FOODS like sauerkraut in your diet. There is good evidence that the vinegar in them – acetic acid – has numerous health properties, including helping reduce LDL cholesterol, stabilising blood sugar and killing pathogenic intestinal microbes.

♥ You are not only what you eat, but when you eat. Ensure AT LEAST 12 (ideally 14) HOURS A DAY WITHOUT FOOD. Stop eating at, say, 7pm, then don’t eat again until 8am. Don’t snack. Drink plenty of fluids. This way of eating lowers blood sugar levels and ensures a stable insulin response. Sugar is fuel for cancer cells.

♥ MODERATE ALCOHOL INTAKE, because when alcohol is metabolised, a compound called acetaldehyde is formed. Acetaldehyde causes DNA damage which raises the risk of heart disease, stroke and some cancers, as well as liver disease and pancreatitis. Whilst most people have enzymatic repair mechanisms, these can be overwhelmed at excess levels – ie averaging more than 2 units of alcohol a day for men – 1 for women. [Ref. Alcohol and cancer: This is how booze damages DNA inside cells (cancerresearchuk.org)]

The newest anti-ageing supplements – ranked!

A huge amount of new research is rapidly improving our understanding of the ageing process and is revealing some interesting compounds.

Often known as ‘biohackers’, the longevity evangelists are mostly using a combination or ‘stack’ of these comparatively newly researched life extension drugs and nutrients.

Here are the main ones, with my comments. It’s purely an overview, so I have only attempted a brief explanation of how each compound may work – leaving you to research any that you think sound worthy of further study.

I have ranked them in order of my assessment of likely impact on health span.

Nicotinamide riboside or NR

This is a form of vitamin B3 that is required in supporting the body to produce NAD+. NAD+ is an essential part of the process of creating energy in cells – which is vital for maintaining all your body systems and in lowering inflammation. But levels of NAD+ decline with age.

NAD+ importantly promotes the production of anti-ageing proteins called sirtuins. These support the repair of DNA and help maintain healthy cognitive function.

Numerous recent studies now confirm that Nicotinamide Riboside extends lifespan in animal models, helps reduce blood pressure and improves cardio-function. [Ref. Emerging Role of Nicotinamide Riboside in Health and Diseases - PubMed (nih.gov)] [Ref. Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin - Vreones - 2023 - Aging Cell - Wiley Online Library] [Ref. Nutrients | Free Full-Text | Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts (mdpi.com)]

Nicotinamide Riboside should be paired with the plant nutrient apigenin because, while NR boosts NAD+, apigenin reduces the consumption of NAD+. So it’s a double action approach, but involving a complicated set of biological pathways – described, however, in an easily understandable way in a video here. NR+A, NAD+ Booster | Boost NAD+ for Healthy Ageing | NutriShield.

Supplementing with CoQ10 also helps increase energy production, but by a different biological process.

Longevity - increasing healthy lifespan NutriShield Multi Vitamins and Minerals — Camomile is a source of apigenin.

Glucosamine

Best known as a key component in cartilage, glucosamine is now known to help in the formation of new mitochondria – a process called mitochondrial biogenesis. It has been found to support autophagy – the process of clearing out dysfunctional proteins that accumulate over time. [Ref. Glucosamine induces autophagy via an mTOR-independent pathway - ScienceDirect] [Ref. Glucosamine Extends the Lifespan of Caenorhabditis elegans via Autophagy Induction (jst.go.jp)]

Recent research shows that a calorie restricted diet does increase lifespan – and glucosamine has been shown to mimic the effects of a calorie restricted diet and help protect against DNA damage. [Ref. Assessment of protective effects of glucosamine and N-acetyl glucosamine against DNA damage induced by hydrogen peroxide in human lymphocytes - PubMed (nih.gov)] . It also helps reduce the cross-linking of tissue fibres that makes them stiff and contributes to ageing.

Higher intakes of glucosamine are correlated to lower mortality in humans. [Ref. Total mortality risk in relation to use of less-common dietary supplements - PMC (nih.gov)].

Berberine

Berberine functions in a similar way to Metformin, a diabetes drug. You can only get Metformin on prescription, as it’s a medication to help reduce blood sugar levels for diabetics – but a large body of research suggests it can also slow ageing.

Berberine (found in the plant Goldenseal) helps balance blood sugar levels and supports metabolic function by activating AMPK, a pro-longevity energy sensor in your cells. It also helps lower blood fats (triglycerides) and a human trial showed it may lower LDL cholesterol – at supplement levels of about 1g a day. [Ref. Berberine decreases plasma triglyceride levels and upregulates hepatic TRIB1 in LDLR wild type mice and in LDLR deficient mice | Scientific Reports (nature.com)]

The cholesterol effect is interesting, but unless you are pre-diabetic, you should be able to achieve stable and low blood sugar levels by severely restricting your intake of sugar and refined carbohydrates, eating mainly plant foods and fasting for 12 hours a day.

Fisetin

Fisetin is one of the more powerful natural compounds yet discovered to help remove senescent cells and produces a positive anti-ageing effect in animal research [Ref. Fisetin is a senotherapeutic that extends health and lifespan - ScienceDirect] . Although in the latest study in mice, fisetin did not extend lifespan.

However, other research suggests fisetin may have neuroprotective properties (i.e. benefits for nerves and brain cells) and may be useful in early cases of as Alzheimer's, Huntington's and stroke.

Fisetin can also help inhibit an enzyme known as MMP-1 which is used by cancer cells to spread within the body. Many of these properties are related to fisetin's antioxidant and anti-inflammatory actions.

Highest concentration is in strawberries, but it occurs in lower amounts in apples, onions, grapes and kiwi fruit.

Resveratrol

Resveratrol is a compound in grapes, grape seeds, blueberries, peanuts and pistachios. Resveratrol has numerous health benefits – including for the heart and brain. It appears to mimic the effect of calorie restriction – which is strongly linked to slower ageing. [Ref. How Resveratrol May Fight Aging | National Institutes of Health (NIH)]

Resveratrol stimulates the activity of enzymes called sirtuins, which are biological pathways known to help counteract the ageing process.

Other compounds known to increase sirtuin activity include grapeseed extract, Omega 3 and fucoidan, a natural organic compound found in some types of brown seaweed. Nicotinamide Riboside boosts sirtuin activity by increasing NAD+ production.

However, in supplement form, the ‘half-life’ of resveratrol is not much more than 15 minutes. Meaning it is poorly absorbed, so a resveratrol supplement would need to start at a minimum of 250mg a day, which is quite expensive. I suggest you get this valuable nutrient through daily berry fruits – grapes, grape juice, blueberries, bilberries, occasional dark red wine and dark chocolate.

Glycine

Glycine is an amino-acid which ‘mimics’ methionine restriction. Methionine is largely found in meat and eggs. But switching more from animal to plant protein also results in significant methionine restriction, as does reducing egg consumption to less than 4 a week.

Glycine also helps clear out senescent cells – through autophagy. As we’ve seen, you can also support the clear-out of senescent cells with fisetin found in strawberries. Other natural compounds that support autophagy, and therefore help remove senescent cells, include vitamin C, curcumin, green tea, green tea extract, Omega 3 and glucosamine.

Spermidine

Research [Ref. New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases - PMC (nih.gov)] detailed in Delay Ageing shows that spermidine plays an important role in many cellular functions, but levels decline over time. Spermidine helps maintain DNA stability by protecting DNA from oxidative attacks. It also promotes autophagy. However, other supplements like green tea extract, grapeseed extract and Omega 3 perform similar functions.

Clinical trials have used from 1-6 mg a day but you can get this level of spermidine from wheatgerm (richest source), from mushrooms, soy foods, broccoli and cauliflower.

Calcium-alpha-ketoglutarate (Ca-AKG)

A study conducted by the Buck Institute showed that this compound reduced frailty and increased health-span in ageing mice [Ref. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice | bioRxiv] .

It is a supplement used in the body-building fraternity because it helps build muscle and indeed is sometimes used in hospitals to speed wound healing. [Ref. Alpha-Ketoglutarate: Physiological Functions and Applications - PMC (nih.gov)] .

Calcium-alpha-ketoglutarate is a natural part of the Krebs cycle, meaning it works by supporting mitochondrial production of energy and that our own bodies create it. But levels decline with age.

In studies on C. elegans – the nematode worm commonly used in longevity research – Ca-AKG supported increased levels of AMPK (which senses energy levels) and the FOXO longevity gene. Both of these lead to increased longevity in animal studies. C. elegans studies also indicate that Ca-AKG stimulates increased autophagy – especially when combined with vitamin C.

Urolithin A

Urolithin A enhances the efficiency of mitochondria and therefore aids energy production. It helps break down and recycle dysfunctional mitochondria, a process known as mitophagy.

Urolithin A is produced in the gut when probiotic bacteria break down ellagic acid. Foods that are high in ellagic acid include berry fruits, walnuts, pecans and brewed tea.

Urolithin A has also been shown to elevate levels of NAD+. A more direct way to increase NAD+ is by supplementing with Nicontinamide Riboside – combined with Apigenin.

N-acetyl cysteine (NAC)

NAC is a form of the amino-acid cysteine. It bonds with glutamine and glycine to form glutathione, an internally produced strong antioxidant.

Antioxidants are compounds that help neutralise free radicals which can damage cells and tissues. Those produced by the body itself are generally even more powerful than externally consumed antioxidants. For this reason, NAC may improve cognitive function. [Ref. A Review on Various Uses of N-Acetyl Cysteine - PMC (nih.gov)].

NAC plays an important role in your body’s ability to detoxify toxins. Some studies suggest that taking NAC supplements can help improve COPD symptoms and lung decline. [Ref. Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on Nutritional and Antioxidant Status of Male Chronic Obstructive Pulmonary Disease (COPD) Patients - PubMed (nih.gov)].

However NAC has low bioavailability. Eating protein foods should provide most people with adequate levels of the amino acid cysteine.

Hyaluronic Acid

Hyaluronic acid is a clear substance that is naturally produced by your body. It is mostly concentrated in your skin, connective tissue, and eyes. Its main function is to keep your tissues lubricated and moist and help in speeding wound healing. However, levels decline with age.

Taking hyaluronic acid supplements can help prevent this decline. by giving your body extra amounts to incorporate into the skin [Ref. Ingested hyaluronan moisturizes dry skin - PubMed (nih.gov)] and into joints – helping lower joint pain [Ref. Oral hyaluronan relieves knee pain: a review - PMC (nih.gov)].

Hyaluronic acid has also been used to treat dry eye.

So hyaluronic acid as an oral supplement can indeed help improve skin quality and reduce the signs of ageing. [Ref. Benefits of topical hyaluronic acid for skin quality and signs of skin aging: From literature review to clinical evidence - PMC (nih.gov)]. But there is limited evidence it will slow cellular ageing itself.

Taurine

Taurine is termed a ‘conditionally essential’ amino-acid – meaning it is only needed when you are stressed or ill. The liver can make it from dietary proteins and it is found in eggs, meat and fish and added to energy drinks. Levels do decline with age.

Taurine helps maintain proper electrolyte balance, hydration and regulates the level of calcium in your cells. Research suggests it can improve immune health and glucose control.

Research also suggests that higher taurine levels are linked to reduced cholesterol, lower blood pressure levels (by dilation of blood vessels), and lower inflammation (as measured by a marker called C-reactive protein). Taurine may significantly lower rates of death from heart disease [Ref. Taurine and atherosclerosis - PubMed (nih.gov)].

However, the research to date on taurine and ageing is based on animal models [Ref. Taurine linked with healthy aging - PubMed (nih.gov)] and even the lead researcher of this study himself cautions that more research is needed [Ref. Functional Role of Taurine in Aging and Cardiovascular Health: An Updated Overview - PubMed (nih.gov)].

Lastly, when taurine is taken along with caffeine, as in energy drinks, it can result in high blood pressure and increased heart rate. [Ref. Taurine, energy drinks, and neuroendocrine effects | Cleveland Clinic Journal of Medicine (ccjm.org)].

Meantime, there are many other nutrients you can take that can improve metabolic health, glucose control and immune function.

Luteolin

Luteolin (not to be confused with lutein) is a polyphenol nutrient found in foods and herbs like radicchio, peppers, celery, parsley, thyme, onions and broccoli. It has been shown to help improve immune function and help protect nerve function.

In animal studies, luteolin helped preserve cognitive function in ageing. But more human studies are needed. [Ref. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype - PMC (nih.gov).]

Lithium (in micro-dose)

Lithium is best known for helping stabilise mood in the treatment of bipolar disorder. But recent research shows it can also – at low doses – reduce the accumulation of damaged proteins in our cells. This plays an important role in ageing. [Ref. Low-dose lithium uptake promotes longevity in humans and metazoans - PubMed (nih.gov)].

Low dose lithium has also been found to help protect the brain – partly by protecting mitochondria. As we age, our mitochondria function less well, meaning cells create less energy.

I believe more research is needed, as there are other compounds that improve mitochondrial function and remove senescent cells.

Prescription drugs

Acarbose (common brand name Glucobay)

An anti-diabetic drug designed to reduce the absorption of starches. Why not just cut down on sugars and refined carbohydrates?

Rapamycin

Rapamycin is an immuno-suppressant drug that was approved by the US Food and Drug Administration (FDA) for use after organ transplants as long ago as 1999.

But over the last decade, researchers have demonstrated the drug’s ability to increase life expectancy in mice and other organisms, when given for short periods. [Ref. Rapamycin and aging: When, for how long, and how much? - PMC (nih.gov)] [Ref. Rapamycin for longevity: opinion article - PMC (nih.gov)] .

Currently Rapamycin is NOT available as a supplement and is only used in the US under strict doctor’s supervision. I believe we need a lot more evidence in humans before anyone should even consider using this drug.

Cellular re-programming – caution!

I have confined this overview to supplements, because they are within the reach of everyone. But highly experimental advanced work on ageing is being done by universities and Big Pharma on ways to actually re-program cells to a younger state. [Ref. Direct cell reprogramming: approaches, mechanisms and progress | Nature Reviews Molecular Cell Biology].

We are years from any human application and the current results of cellular programming “show promise but there are safety concerns”. [Ref. Cellular reprogramming and epigenetic rejuvenation - PMC (nih.gov)].

That's rather an understatement. In one of the latest studies on mice, which had some of their genes re-programmed, they started developing non-benign tumours called teratomas.

Conclusion - SIMPLIFY

It’s time to try to simplify!

Your baseline healthy diet plus comprehensive health supplement

⊕ The fundamental basis of healthy lifespan is a good diet low in sugars and refined carbs. We believe we have defined that using decades of peer reviewed research. See Healthy Eating Plan | NutriShield

⊕ The common sense baseline, healthy ageing supplement is one that gives you more of the protective nutrients in that ideal diet – because you need an increasing levels of quality nutrition to counteract increasing cellular damage as the years go by. That’s why we created NutriShield. Unique Health Supplements UK | NutriShield

On top of these you should consider:

⊗ The need to counteract the normal decline in NAD+ and therefore decline in your cellular energy levels. This decline drives ageing and age-related illness.Several compounds can help do this – including Calcium-alpha-ketoglutarate, Urolithin A and Nicotinamide Riboside.

I believe Nicotinamide Riboside (a version of vitamin B3) has the best supporting research. That’s why we introduced our NR+A. NR+A, NAD+ Booster | Boost NAD+ for Healthy Ageing | NutriShield. (The alternative B3 compound NMN or Nicotinamide Mononucleotide has NOT been passed as safe in Europe).

⊗ There is a need to reduce the accumulation of senescent cells as we get older – the other key driver of ageing. Fisetin, quercetin, glycine and spermidine all activate autophagy ie. help clear senescent cells.

But so do curcumin, EGCG in green tea, genistein in soy, glucosamine, Omega 3 and nicotinamide. These are all in NutriShield Premium. If you want to add an additional compound to help clear senescent cells, I would probably choose fisetin – or eat a regular large bowl of strawberries.

⊗ None of the longevity compounds we have reviewed addresses microbiome health, but this is undoubtedly a major factor in extending your health span. We have just completed a full review of the latest evidence.

I hope this review has been helpful. I am not a bio-hacker – but I do believe the new research is revealing some supplements that are worth keeping an eye on. Although for most, more evidence is needed.

Nothing replaces the common sense of following a real food plan that is based on hundreds of years of evidence – supported by a supplement that adds more of the most protective nutrients in that food plan.

Delay Ageing book explains the ageing process and how you can postpone it

Medical researchers agree that if you slow ageing, you also delay the onset of age-related disease. And we know that it’s not just nutrition. Sleep, reducing stress and cardio and strength exercise are also essential to longevity and ageing well.

My book Delay Ageing: Healthy to 100, published in 2020, explains the latest ageing science in an accessible way.

It’s been rated 5-star and I am sure you will get a lot of benefit from it, as so many have already.

Click here to go to the publisher's website where you can buy the printed book or Kindle version.

Longevity – increasing healthy lifespan

How you can beat the billionaires at their own game