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If you want to crack the longevity code, then one of the best places to start is exercise (see my post about exercise here) and nutrition. Here’s what research of some of the top longevity scientists reveals about nutrition and their own dietary habits.

Drs Elizabeth Blackburn and Elissa Epel

Dr Elizabeth Blackburn (with Carol Greider, and Jack Szostaks) won the Nobel Prize for medicine in 2009  "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase."

Telomeres are the molecular caps that protect chromosomes – acid molecules containing the genetic material of our body.

Each time a cell divides and its DNA is copied, the telomere shortens. The shorter the telomere, the older you look and feel, and when they can’t divide any longer… well you die.

In her book (with Dr Elissa Epel, PhD) The Telomere Effect, Dr Blackburn explains the enemies of telomeres and cellular health. Inflammation, insulin resistance, and oxidative stress create an environment that is toxic for telomeres and cells. Think of these conditions as three sneaky villains that hide inside each of us.

How do you protect your telomeres and stimulate telomerase activity? Through a healthy lifestyle - managing chronic stress, exercising, eating better and getting enough sleep as well as telomere testing. Be wary of clinical pills claiming to lengthen the telomeres and protect the body from ageing (they have no scientific proof behind them).

You can eat foods that feed these three villains—or you can eat foods that fight them, shifting the cell environment to one that is healthier for telomere upkeep.

Telomeres and nutrition

Some foods and supplements promote healthy telomeres, while others don’t, according to Drs Blackburn and Epel:

 

Associated with Shorter Telomeres Associated with Longer Telomeres
Red meat, processed meat Fiber (whole grains)
White bread Vegetables
Sweetened drinks Nuts, legumes
Sweetened soda Seaweed
Saturated fat Fruits
Omega-6 polyunsaturated fats (linoleic acid) Omega-3s (e.g., salmon, arctic char, mackerel, tuna, or sardines)
High alcohol consumption (more than 4 drinks per day) Dietary antioxidants, including fruits, vegetables, but also beans, nuts, seeds, whole grains, and green tea
Coffee
Iron-only supplements (probably because they tend to be high doses) Vitamin D45 (mixed evidence)
Vitamin B (folate), C, and E
Multivitamin supplements (mixed evidence)

Blackburn and Epel’s Test

You can also do this simple test (taken from The Telomere Effect) to see whether your nutritional habits promote longer telomeres.

How often do you have the following? Circle 1 or 0 for each question.

1. Omega-3 supplements, seaweed, or fish that contains high omega-3 oils 3+ servings per week 1
Less than 3 per week 0
2. Fruits and vegetables At least daily 1
Not every day 0
3. Sugared sodas or sweetened beverages (not including when you add sugar to coffees or teas, which typically adds up to substantially less sugar than in commercially sweetened drinks) At least one 12-ounce drink on most days 0
Not regularly 1
4. Processed meat (sausage, lunch meats, hot dogs, ham, bacon, organ meats) Once a week or more 0
Less than once a week 1
5. Whole foods (whole grains, vegetables, eggs, unprocessed meats) vs processed food (packaged or processed with salts and preservatives) Mostly eat whole foods 1
Mostly eat processed foods 0
YOUR TOTAL SCORE (SUM OF 1-5)

Key:

  • If you scored a 4 or 5, you have excellent telomere protection from diet.
  • If you scored a 2 or 3, you have average risk.
  • If you scored 0 or 1, you have high risk.
  • The frequencies are extrapolated from telomere studies.

James Clement and Dr George Church

James Clement, a lawyer and entrepreneur turned research scientist, co-author of The Switch, is best known for his Supercentenarian Research Study, which he started in 2010 with Professor George M. Church of Harvard Medical School. One of Clement’s main interests is autophagy, and this is how Dr Church explains it:

One of the most fascinating discoveries of late has been an intriguing process called autophagy. Although we in the scientific community have been studying this biological activity for decades, only in 2016 did the research finally culminate in a clear understanding about it and earn a Japanese cell biologist, Yoshinori Ohsumi, the Nobel Prize for his contributions. The word literally means “self-eating,” but as you’re about to read, it’s not as horrifying as it sounds. Autophagy is simply the body’s natural way of recycling and renewing its parts to avoid disease and dysfunction. It’s a process that has been conserved in the genetic code of life for billions of years, so yes, it even predates us humans.

Autophagy is how your body removes and recycles dangerous, damaged particles and pathogens from your cells. This boosts your immune system and significantly reduces your risk of developing cancer, heart disease, chronic inflammation, osteoarthritis and neurological disorders. Autophagy can be triggered when a certain complex, called mTOR, within cells is turned down. mTOR is the major nutrient-sensitive regulator of growth and plays a central role in physiology, metabolism, the aging process and common diseases.

When mTOR is activated, autophagy is suppressed, and when mTOR is silenced, autophagy is enhanced. This mechanism controls whether the cell is in an anabolic (growth) phase or in a catabolic (housecleaning) phase. Cycling back and forth between activating autophagy and mTOR is currently believed to be the best anti-ageing “switch” that we know of. It already exists within you. This metabolic switch seems to be activated by diet, particularly by calorie restriction, intermittent fasting, and very-low-carb (ketogenic) diets.  Clement, by his own account, took a deep dive into experimenting with these diets.

Activating the Switch

So what do you need to do to activate The Switch? According to Clement,

  • Consume less animal protein and dairy products to turn down mTOR. This is how you enter a catabolic state, in which autophagy turns up and your body cleans out the waste.
  • Consume fewer high-glycemic carbs (i.e., sugars, flours, easily digested starches, and many fruits) to lower your blood glucose level, turning down mTOR.
  • Ditch all refined carbs (cereal, chips, pasta, cookies, energy bars, sports drinks, etc. and all packaged foods, especially “low fat” or “fat-free”) and all natural (honey, brown sugar, agave, maple syrup and table sugar) and artificial sweeteners.
  • Consume a low enough level of carbohydrates (less than 20 grams a day), so that you continually produce ketones and are thus in a ketogenic state. Not only does this turn down mTOR, but can improve your brain function, enable you to fast more easily and help you to burn fat to improve your health and lose weight faster.
  • Choose foods that are anti-inflammatory and avoid those that are pro-inflammatory (e.g., avoid foods high in omega-6 fatty acids and increase your intake of omega-3 fatty acids).

The key to long-term good health is cycling your diet so that you’re in a catabolic (housecleaning) state about eight months a year and an anabolic (growth) state the other four months. You can break it down whichever way you want – for example, two out of three months. This pattern will provide your body with periods of renewed growth of stem cells and a stronger immune system while replenishing muscle and some fat.

Autophagy is also induced by certain nutraceuticals (e.g., caffeine, turmeric, ginger, quercetin, resveratrol), pharmaceuticals (metformin and rapamycin) and exercise.

Dr David Sinclar

Dr David Sinclair is professor of genetics at Harvard Medical School, one of the most influential people in the world (Times, 2014), an entrepreneur and an outspoken anti-ageing advocate. He’s also the author of Lifespan: Why We Age and Why We Don't Have To. As you can guess from the subtitle, Dr Sinclair is a big believer that ageing is a choice. You can read a plain language explanation of his work here.

Dr Sinclair and his lab colleagues study the malfunction of a family of proteins known as sirtuins as the single cause of ageing. Sirtuins are longevity genes controlling DNA reproduction and repair. As we get older, all the genetic information in our cells is still intact, but our body loses the ability to interpret it, because it starts to run low on NAD (nicotinamide adenine dinucleoticide) molecule that activates the sirtuins. We have twice as much NAD at 20 than we do at 50. Without NAD, the sirtuins can’t do their job, and the cells in our body “forget” what they’re supposed to be doing.

It’s not a surprise that Dr Sinclair receives multiple queries each day regarding what he does to keep himself healthy. He claims his heart’s biological age is 30 (Dr Sinclair is in his early 50s), and he hasn’t got a single gray hair. In his book he breaks down his own anti-ageing regimen (with the caveat that he’s not a medical doctor and can’t give advice). In addition to nutrition, it includes activities that are proven by science to extend our lifespan – such as certain types of exercise and extreme temperature stress – as well as regular blood tests for biomarkers.

Here is what Dr Sinclair says he does in terms of nutrition and supplementation in Lifespan:

  • I take 1 gram (1,000 mg) of NMN [nicotinamide mononucleotide, NAD booster] every morning, along with 1 gram of resveratrol (shaken into my homemade yogurt) and 1 gram of metformin.
  • I take a daily dose of vitamin D, vitamin K2 and 83 mg of aspirin.
  • I strive to keep my sugar, bread and pasta intake as low as possible. I gave up desserts at age 40, though I do steal tastes.
  • I try to skip one meal a day or at least make it really small. My busy schedule almost always means that I miss lunch most days of the week.
  • I eat a lot of plants and try to avoid eating other mammals, even though they do taste good. If I work out, I will eat meat.

As you can see, much of the nutritional recommendations from leading scientists is just straightforward common sense. You can decide for yourself which of these make most sense to you. I’m personally very skeptical about the dangers of red and organ meat (some very large-scale studies suggests otherwise) or that consuming whole grains for fiber is good for you. I’m a big fan of a plant-based diet, but can’t live without some meat, seafood or a glass of red vino (which is where you will find resveratrol naturally).

Disclaimer: Although I hold a PhD and understand how rigorous research should be done, I’m not a medical scientist or doctor, so nothing in this post should be taken as nutritional advice. Always DYOR and consult your medical practitioner.

Extending lifespan is a popular topic, but how about your skinspan?

How much have you recently spent on a jar of another anti-ageing cream? What did it promise?  To slow down the loss of elasticity, boost collagen levels, visibly smooth fine lines and wrinkles, restore firmness? How much did it deliver?

Enter a new generation of anti-ageing skincare.

In my earlier post I wrote about senolytics, or zombie cell killers, that remove senescent cells. One of the most promising applications is the use of topical rapamycin for skin photo-ageing and volume loss. The product has undergone a small-scale human trial with promising results, but it's still unclear when it will be fully commercialised.  Which is why OneSkin by OneSkin Technologies, just launched into the market, and claiming to reduce the molecular age of skin cells, is such a newsworthy development.

Meet OneSkin Technologies

OneSkin Technologies is on a mission to transform the way we think about skin.

It's a Brazilian startup (now headquartered in California) founded by four PhD holders - Carolina Reis Oliveira (CEO), Alessandra Zonari, Mariana Boroni and Juliana Carvalho.  Yes, they are ALL women! The startup was launched in 2016 after being accepted into  IndieBio, one of the world’s leading science accelerators. Its team includes Lear Brace, Senior Scientist, a Harvard PhD and Postdoctoral Fellow at the Buck Institute for Research on Aging and Peter Diamandis as one of its advisors. The startup raised $2M (2017, seed round), $3.5M (2019, post-seed) and $1.5M (2020, angel investment).

The CEO describes how they came about developing OneSkin:

Our roots are in longevity science and we saw a need to shift the current paradigm. Instead of short-term fixes that focus purely on aesthetics, we’re targeting the root cause of aging and optimizing skin health on a molecular level. We believe what we put on our skin should be safe, effective, and help to maximize our human potential.

Biotech startups are very risky, which is why OneSkin Technologies were initially hoping to de-risk their business model by providing testing services for other pharma companies. But then - with the encouragement of venture capitalists - they realised that  they could use their testing platform to develop own molecule.

OneSkin Technologies measure skinspan with MolClock – a skin-specific molecular clock – and with skin ageing modelling, using a proprietary technology and lab process. This involves growing 3D human skin weekly and measuring how various products and ingredients influence gene expression of the many genes associated with ageing and longevity. MolClock (launched in August 2020)  is an Application Programming Interface (API) and is available for free and public use.  Arguably,  it can provide information on the organism just like a car panel provides information on the car. You can run your test here.

OneSkin Technologies' CEO outlines the startup's ambitions:

It is a unique experience to pull these things together: Growing different kinds of skin that are more representative of the consumer’s skin we want to treat; aging the skin, developing an algorithm to measure the aging; and then reprogramming the skin cells to not just stop aging, but go backwards a little bit.

How effective is OneSkin?

OneSkin is marketed as "the first topical supplement designed to extend your skinspan on a molecular level". It contains  a proprietary peptide, OS-01. Designed to reduce skin’s biological age, OneSkin claims to reduce your skin's biological age, improve skin barrier and support proper cell function. The results are seen in about 4-8 weeks with daily use.

This marketing strategy - as a cosmetic product, not a drug - doesn't in any way belittle the cream's efficacy. Rather,  it's a reflection of  a clever (and faster) pathway to regulatory approval taken by the startup team. Although the startup classify their cream as "cosmetics", this is only a regulatory term for the purposes of FDA approval. It is perfectly possible for a topical product that is regulated as a cosmetic to have therapeutic effects, just like a drug. Despite the general feeling that cosmetics in the U.S. are hardly regulated by the FDA, the number one rule is safety (i.e., the product should do no harm to the skin) plus appropriate labelling.

In 2019, Carolina Reis Oliveira, the CEO of OneSkin, described the R&D process as a combination of biology and ML:

Our lead candidate molecule is a new synthetic peptide, which was initially screened in a synthetic library for antimicrobial peptides (AMP). AMPs have multifunctional behavior and accumulate several interesting properties for skin applications, including tissue repair, antioxidant activity, collagen synthesis, anti-inflammatory activity and we decided to evaluate their senotherapeutic potential.

From our initial 200 library, we selected 4 hits - the 4 compounds which were most effective in decreasing senescent cells in human skin. Then, we used an algorithm to create variations of such sequences, leading to hundreds of possible leads. Among those leads, we selected the two best peptides, deemed OS-1 and OS-2, which have consistently shown the ability to decrease human cellular senescence caused by aging, ultraviolet light, and other types of genotoxic stress by 25-50%.

The startup team tested many other senolytics known in the research literature. Eventually none of them seemed to induce apoptosis (programmed cell death) in senescent cells, while some were toxic to non-senescent cells.  OS-1 and OS-2 proved the most promising, in the end the cream was developed with OS-1 as the active molecule. As a reminder, it's a new synthetic peptide, meaning it's not completely naturally occurring in the body.

Most of the high-performing creams and serums you and me use today contain retinol. According to the team, OS-1 performs better than retinoic acid (a form of Vitamin A), currently considered the gold standard molecule for anti-ageing skin care. Retinoic acid does, however, have multiple side effects and may cause inflammation.

 

Disclaimer: This is not an endorsement of the OneSkin cream. Always DYOR. But I will certainly be testing OneSkin on my own skin!

 

I don't know of any individual who hasn't been affected by cancer, either directly or indirectly. It’s one of the most frightening words in human vocabulary.

In the U.S. alone, there are in excess of 1.7 mln new cancer cases diagnosed and over 600,000 deaths each year (2019 data). We can only hope that “the cure for cancer” comes quickly.

We have seen tremendous progress in many technology areas recently, such as software and machine learning. Progress in computing, best described by Moore’s law, has been exponential and nothing short of spectacular. In Artificial Intelligence, after a prolonged winter, spring has finally arrived. But progress in biotechnology and drug discovery has been disheartening. Eroom’s law – Moore’s law spelled backward – suggests that drug discovery has become slower and more expensive over time: the number of new drugs approved per billions of dollars in R&D has halved every 9 years since 1950.

And this is why I am excited to see that things are changing. I was recently listening to a podcast by Andreessen Horowitz, a leading Silicon Valley venture capital firm investing in biotech, on the past, present and future of cancer research and treatment. A new revolution is on the horizon, and even now we have powerful tools – both high-tech and very low-tech, low-hanging fruit solutions – available. This is a summary of the podcast, together with recommendations regarding what you can do to prevent cancer and my links to various resources.

The first three revolutions

For the most of 150 years, since first treatments, scientists and doctors had no understanding of what happens at a cellular, let alone molecular level. To put present progress in perspective, this is where we’ve come from:

1882 – The first radical mastectomy to treat breast cancer (after the invention of anaesthesia)

1896 – Treatment of breast tumor with radiation after the discovery of x-rays (in 1895)

1940s – First treatments of children with acute leukemia using chemotherapy.

These innovations (surgery, radiation therapy and chemotherapy) launched the first revolution and a whole new era of systemic treatment. They are still the mainstay for certain types of tumours, where targeted therapies don't help. For the most part of this period the fight against cancer was a fight against symptoms, as there was no explanation how cancer occurs in the first place. These were blunt tools – let’s kill the tumour rapidly!

But eventually scientists figured out the hallmarks of cancer. Cancer occurs because of changes in cell states, as cancerous cells learn how to grow out of control, resist our immune system and even secure their own blood supply.

The 2nd revolution started in the 1990s, with a move toward genomically targeted therapies and an attempt to identify a unique genetic driver of cancer cell division. It the past tumours used to be identified as organ-specific, now it was possible to look at cancer biology in a tumour-agnostic way and at a cellular level. This was the era of precision medicine, when a treatment could be applied to switch off the faulty gene. So you could take a cancer cell’s strength (uncontrollable division), and turn it into a weakness.

The 3d revolution in cancer treatment is immunotherapy. Rather than targeting tumours with precision bombs (i.e., targeted therapies), it’s boosting an individual’s immune system. It can complement other approaches, allowing a body’s own T-cells (cancer killer cells) to fight solid tumours. Another therapy, CAR T-Cell therapy harvests the cells from an individual and engineers them to attack cancer cells in liquid cancers. Cancer vaccines, aimed at recognising and destroying cancer cells in a highly personalised fashion, are also at the leading edge of treatments. This field has exploded in the last decade.

In 1991-2015, due to awareness, prevention and early detection, mortality was decreased by 27%, and between 2015-2035, scientists expect a further 40% reduction. We’re entering a period when we’re getting closer to a day when cancer may be managed as a chronic disease.

Present and future of cancer treatment technology 

The next generation of therapies will have a lot to do with a brand new understanding of chromosomal DNA. For example, in many solid cancer cells researchers can detect circular DNA which are outside chromosomes, driving the growth, recurrence and resistance of tumours in a way that’s very different from current understanding. It’s a sneaky mechanism that cancer cells use to evade therapies, and targeted therapies can exacerbate the growth of these circles. If it can be complemented with chemotherapy and immunotherapy, this could be a paradigm shift in cancer treatment.

The 5th revolution is metabolic therapy, where nutrition – such as wholefood, plant-based diets, calorie restriction and ketogenic diets – plays a key part. Targeting glucose dependency of cancer cells, boosting metabolic efficiency of healthy cells, cutting-edge techniques (e.g., involving microbiome) – all this will enhance our understanding of our bodies holistically, from a high-tech and low-tech perspectives.

What can you do now to fight cancer?

Nearly 50% of deaths are caused by risk factors that you can control – essentially, they are related to your lifestyle.

A low-tech approach to preventing cancer

  • Quit smoking – lung cancer is the second most common type of cancer, and the leading cause of cancer death.
  • Eat healthy – foods (which you take 3 times a day) are as consequential for your health as the drugs you take.  If you’re confused what to eat and need a clear roadmap, I can highly recommend Food: What the Heck Should I Eat? by Mark Hyman, MD.
  • Exercise regularly – I have written on high-interval intermittent training and its anti-aging effects, and hence prevention of age-related diseases such as cancer and dementia. Try weights and bodyweight resistance training as well. Mark Lauren has developed uncomplicated programs for men and women for bodyweight resistance training.
  • Do checkups – early detection is critical to preventing cancer.

“Ageing is a natural process and there’s nothing you can do about it.” Right?

Wrong… but how often do you hear this popular refrain?

There is a difference between popular opinion on the one hand, and scientists and technologists on the other hand – and the people behind them, such as venture funds and private philanthropists. They treat “ageing” as a challenging problem to be solved, not a natural and unavoidable process. Thanks to some of the technologies available now and in future a longer, healthier lifespan is inevitable.  There is no biological law that says that you MUST age.

Why do we age?

Like with any complex phenomenon, explanations of ageing have evolved over the years, from rather simple (such as being caused by free radicals) to more nuanced. Within the latter category, there is a view that aging and the diseases that come with it are the result of multiple “hallmarks” of aging – in fact, 9 such hallmarks:

  • Genomic instability caused by DNA damage
  • Attrition of the protective chromosomal endcaps, the telomeres
  • Alterations to the epigenome that controls which genes are turned on and off
  • Loss of healthy protein maintenance, known as proteostasis
  • Deregulated nutrient sensing caused by metabolic changes
  • Mitochondrial dysfunction
  • Accumulation of senescent zombielike cells that inflame healthy cells
  • Exhaustion of stem cells
  • Altered intercellular communication and the production of inflammatory molecules
9 hallmarks of ageing
Source: Cell.com 

Dr David Sinclair, the author of Lifespan, believes that there is a singular reason why ageing occurs and what lies beneath the nine hallmarks of ageing. Yes, a single reason why we age. Aging, quite simply, is a loss of information, digital and analog. Our DNA is akin to digital information, which can be stored and copied again and again with tremendous accuracy. It’s no different in principle from digital information stored in in computer memory or on a DVD. This digital information lasts way longer than 80 years (this is a new discovery).

Analog information is more commonly known as the epigenome (i.e., heritable traits that aren’t transmitted by genetic means.) The epigenome is the structures within the cell that allow some genes to be read while keeping others silent. Because the analog information is very hard to preserve, it’s the first one to fail. And this is what, according to Dr Sinclar, causes ageing.

Longevity genes

One of the most exciting discoveries in recent decades was that there are genes that control aging – so-called longevity genes. These genes don't just make life longer, they also make it healthier, which is why they should be really called “vitality genes”. Here are some of the better-studied genes, together with their functions:

Sirtuins This group of enzymes regulate a variety of metabolic processes essential to maintain proper cellular function (incl. the release of insulin, mobilization of lipids, and response to stress).
Rapamycin / mTOR mTOR improves cell survival by boosting such activities as DNA repair, reducing inflammation caused by senescent cells and digesting old proteins (autophagy). It helped our ancestors to survive periods of famine when proteins were not available.
APMK Is a metabolic control enzyme which evolved in response to low energy levels.
KLOTHO Improves brain skills such as thinking, learning and memory regardless of age, sex, or a genetic risk factor for Alzheimer’s disease.

 

These genes are activated in the time of biological stress.

Ready to hear about the three breakthrough anti-ageing technologies?

They are already a reality in humans and human tissues, and not just animals.

Technology #1: Senolytics – “zombie cell” killers

Senolytics are anti-ageing drugs, they work by removing certain cells that accumulate as we age. During ageing our cells eventually lose their identities and cease to divide, in some cases sitting in our tissues for decades. Zombie cells secrete factors that accelerate cancer, inflammation and help to turn other neighbouring cells into zombies. It’s hard to reverse aging in senescent cells, so the best thing to do is to kill them off, which is what senolytics do. These drugs will not enable you to live longer as yet, but they treat specific ailments by slowing, halting or reversing a fundamental process of ageing.

A number of senolytics are now in human trials to treat debilitating diseases:

Mental illnesses (Alzheimer’s disease, Parkinson’s and dementia) - Alkahest, a clinical stage biotechnology company, hopes to halt cognitive and functional decline.

Skin ageing – a group of researchers conducted a trial into into whether immune-supressing drug rapamycin can slow photoageing and dermal volume loss and increase collagen. It did… although the study is exploratory and yet to be extended in clinical settings.

Technology #2: Stem cell therapy for AMD

Advanced “dry” age-related macular degeneration (AMD) is a leading cause of blindness in adults over 50. We humans lack the innate ability to regenerate retinal tissue and replace lost retina cells. This led us to believe that progressive disease may be slowed or halted, but not reversed.

But researchers from Lineage Cell Therapeutics, a clinical-stage cell therapy company, proved otherwise. They demonstrated a clinical breakthrough with regeneration of retina using RPE stem cell injection. These results are unprecedented. If they can be replicated in larger clinical settings, this study is likely to go down in history as a turning point for regenerative medicine. You can find images from the study here.

Technology #3: Human cell rejuvenation

Can your cells be re-programmed back to a youthful state?

While this may sound like magic, this is exactly what a group of Stanford University researchers have done.

They hope that the technique will help in the treatment of diseases, such as osteoarthritis and muscle wasting, that are caused by the aging of tissue cells. In this study the researchers utilised powerful agents known as Yamanaka Factors (Dr Shinya Yamanaka received the Nobel Prize in medicine in 2012)which re- reprogram a cell’s epigenome to its embryonic state.

The Stanford team extracted aged cartilage cells from patients with osteoarthritis and found that after a low dosage of Yamanaka factors the cells no longer secreted the inflammatory factors that provoke the disease. Human muscle stem cells, which are impaired in a muscle-wasting disease, could be restored to youth, too.

Turn Biotechnologies (the company set up by the researchers to commercialise the technology), is working on developing therapies for osteoarthritis and other diseases.

Other exciting therapies are underway, they have been done successfully in mice, and it’s only a matter of time before they can be replicated in humans.

What can you do now?

The rejuvenation roadmap is long, with many stages, and requiring a rigorous regulatory approval to ensure that the drugs and therapies are safe. These breakthrough technologies are not yet available to you and me. Senolytics, according to the MIT Technology Review, will be available within 5 years. It may take even longer for AMD stem cell therapy and cell rejuvenation for arthritis and muscle wasting (and it’s unclear whether lab results are transferrable to humans).

Other therapies (e.g., gene therapy) are costly and are not widely accessible. Is there anything that you can do right now?

Absolutely! Here’s the good news…Your longevity genes are activated by stressors.

When we’re exposed to challenges and hardships (starvation, toxins in small doses, infections, heat and cold), they all can lead to a longer life. There are plenty of stressors that can turn them on without cell damage, and many of them are virtually free. All these are pretty much low-tech solutions.

Caloric restriction (CR) and fasting are anti-ageing

Consuming less food is good for you!

CR means limiting the number of calories consumed each day, while avoiding malnutrition. When caloric intake is low (as when you’re in the fasting state), your cells switch into protective mode, activating the rejuvenation process. CR has a powerful protective effect against obesity, type 2 diabetes, inflammation, hypertension, cardiovascular disease and reduces metabolic risk factors associated with cancer. It also improves markers of cardiovascular ageing and rejuvenates skeletal muscles. CR boosts the function of longevity genes (sirtuins, APMK, mTOR), blocks cellular senescence and encourages autophagy (cellular “housekeeping”, or removing older and damaged components inside cells).

Even though studies in humans are sparse, there are plenty of studies in rodents and mammals. For example, one study shows that CR significantly improves age-related and all-cause survival in monkeys on a long-term ~30% restricted diet since young adulthood. In one rare study of Okinawans (aged 65+) it was clear that their borderline CR diet contributes to low risk of mortality from age-related diseases, and extended mean and maximum life span.

CR is not without its critics and may not be sustainable long-term, and so should be done with caution. But what we know today is that modest forms of CR with optimal nutrition need to be taken at least as seriously as exercise for increased longevity.

It’s possible to have anti-ageing benefits without having to go hungry with CR diet. The so-called fasting-mimicking diet (low in calories, sugars and protein, but high in unsaturated fats), practiced for 5 days a month for three months (and repeated, if needed), is believed to be safe and effective for longevity.

I personally find intermittent fasting quite easy, particularly when I’m busy at work.

Exercise (HIIT and RT) increase longevity

Exercise switches on the genes to make you young again at the cellular level. I have written about the benefits of high-intensity training (HIIT) for longevity previously. Being out of breath for 10-15 minutes every other day is actually a good thing, as HIIT has been linked to a reduction in different diseases, particularly heart diseases.

As we get older, we tend to lose muscle mass, sometimes by as much as 70% in our third age. Resistance training (RT) is without question the most efficient method that helps you to retain your muscle strength and bone density, so that you continue to have an active and independent lifestyle. Regular, progressive training can also reserve aspects of ageing at the gene level and lower the risk of mortality.

Gyms are not an option for many of us right now, but there’s a wonderful alternative. Bodyweight resistance training requires no to minimum equipment and can be done anywhere.

Hot and cold temperatures as stressors

What is optimal for longevity – staying “cool” or being “hot”?

Temperature is a basic and essential property of all living creatures. Slightly lowering the core body temperature in warm-blooded animals for prolonged periods of time can extend lifespan by 20% (unfortunately, it’s not practical for humans to attempt to do the same). Cold seems to activate a certain temperature-sensitive channel (found in nerve and fat cells) which in turn activates a gene associated with longevity.

Incidentally, this gene can also be activated by wasabi (Japanese horseradish), so perhaps we should all go to sushi restaurants more often! In parenthesis, caloric restriction also lowers your body temperature. However, if you choose to expose yourself to cold, moderation is key, as hypothermia is detrimental to your health.

What happens if you decide to use hot temperature as a stressor? Science is less clear, although some lab studies show that raising temperatures in single-cell organisms just below the threshold they can endure can increase their lifespan by 30%. It seems to work in humans, too. According to one large-scale study, Finnish men who are frequent sauna users have a much lower incidence of heart disease and heart attack.

You decide which way you want to go!

How much do you know about HIIT exercise? Exercise is physical stress applied to the body.

Different types of exercise can stimulate specific responses in our bodies: 

  • Aerobic exercise improves insulin sensitivity.
  • High-intensity interval training (HIIT), which involves repeating short bouts of activity at near-maximal intensity, rapidly increases aerobic capacity, mitochondrial respiration, and insulin sensitivity.
  • Resistance training (RT) reverses age-related declines in synthesis rates of muscle proteins
  • Combined training (CT) offers many benefits of both aerobic and resistance training, although the intensity of aerobic and resistance components are lower than either HIIT or standard RT programs.

But are all types of exercise born equal, when it comes to longevity and rejuvenation? As it turns out, the answer is NO.

To engage your genes fully, the intensity of the exercise does matter, suggest Dr David Sinclair, a prominent longevity researcher.  It’s high-intensity interval training (HIIT)—the one that significantly raises your heart and respiration rates—that engages the greatest number of health-promoting genes, and more of them in older adults who exercise. A reputable study by researchers at the Mayo Clinic shows that these changes are more dramatic in the over-65 exercisers compared with a group of people under age 30 who did the same workouts.

Even through runners have used HIIT for well over a century to improve their endurance, HIIT didn't go mainstream until about a decade ago. Following multiple studies that repeatedly showed the benefits of HIIT, the routine was popularised with the seven-minute workout and even a one-minute workout!

Why is HIIT exercise so beneficial?

Reason #1 - HIIT is anti-ageing

Scientists know that many of the longevity genes that are turned on by exercise are responsible for the health benefits of exercise. These benefits include extending the length of telomeres (these proteins are good indicators of our biological clock) which protect us from genome degradation. In addition, exercise helps to grow micro-vessels that deliver oxygen to cells  and boosts the activity of mitochondria, which burn oxygen to make chemical energy. Mitochondria contain genes coding for proteins important in energy production. They are the powerhouses of the cell.

Unfortunately, these bodily activities fall as we age. But the good news is that the genes most impacted by exercise-induced stress can bring them back to the levels associated with youth. HIIT provides the stress necessary to stimulate production of the naturally occurring hormones (testosterone, growth hormone and insulin-like growth factor 1).  These steroids promote muscle protein synthesis and increase lean muscle mass and so help to mitigate the effects of the aging process.

But the news gets even better!

Reason #2 - HIIT improves memory

HIIT also helps to improve memory. Older adults who exercise using HIIT show up to 30% memory improvement, while older adults working out moderately see no improvement.  In one particular study, older adults (between ages 60 and 88)  were monitored over a 12-week period and participated in three sessions per week. Some performed high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), while a separate control group engaged in stretching only.

Those who participated in HIIT did 4 sets of exercise on a treadmill for 4 minutes.  The MICT protocol was a lot longer - one set of moderate-intensity aerobic exercise for nearly 50 minutes. A special test (which taps into the function of the newborn neurons generated by exercise) was used to measure memory improvements.

The conclusion? It's never too late to start to exercise... but if you do start late, make sure your you do HIIT.

Reason #3 - HIIT helps you to shed weight

Do you have a few pounds that you would rather not have, but don't want to spend hours in the gym? I certainly don't.

You can burn more calories with HIIT (25-30% more) than with a regular cardio exercise within the same amount of time. This is a perfect solution for those of us who want to gain the benefits of both resistance and cardio training, but have limited time to exercise. A regular HIIT session can take only 10-30 min.

And the best part of HIIT exercise?

This rejuvenation pill costs you nothing and is equipment-free.

How to measure "intensity"

"High intensity" is rather subjective, but you can can still measure it. It feels challenging:

  • Your breathing is deep and rapid.
  • You develop a sweat after only a few minutes of activity.
  • You can't say more than a few words without pausing for breath.

Trainers will often talk about heart rate zones, which are a percentage of your maximum heart rate.  Here's how to determine yours:

Substract your age from 220.

For example, at age 55 you should aim to get your heart rate to around 132 beats a minute (80% of your 165 max heart rate) during each interval, which can last from 30 seconds to a few minutes. Bear in mind that maximums differ significantly from individual to individual regardless of fitness, and a higher max heart rate doesn’t necessarily mean you’re more fit.

 FitBit or heart rate monitor can also help.

Get results today!

To get full benefits of HIIT, you only need to exercise 2-3 times a week. A big component of this type of exercise is getting enough recovery time. Consistency and variety (combination with other activities) is what will keep you motivated.

A word of caution - like with any exercise, a prior clearance with a medical practitioner is highly recommended. Counterindications include excessive weigh, heart disease and hypertension.

Here are links to workouts to get you going:

  • 4 x 4 routine (clinically tested), where a researcher explains how and why you should do this exercise.
  • 12 station program, includes 30 sec of exercise followed by 10 sec rest, 7 minutes in total for a circuit.  All exercises can be done with body weight and in almost any setting (home, office, hotel room, etc.).
  • a series of 10-15 min. workouts

Get started NOW!

I’ve been a late starter in life. I’m determined to make my third age the most productive, fulfilling and happy period in my life, no matter what.  I’m inviting you to join me on this journey.

I called the blog The Fringe. I believe that everything significant happens at the fringe, this is where the most powerful ideas are born – the Internet, PCs and cryptocurrencies.  Here’s one fringy idea to start with.

I’m excited that modern science might have an answer to the question of longevity in my lifetime. What may sound like science fiction to you right now is becoming a reality. I will be writing about these scientific and technological breakthroughs, so that you can directly benefit from them too. I will also be writing about how you can do whatever you like in your third age – learning new skills, changing a career, completing your PhD, writing a bestseller book, or starting a business and getting venture capital. Yes, the latter is not a fantasy! There are now investor funds focusing on older entrepreneurs.

Do you know that ageing is a disease? In 2018, the World Health Organisation released a new International Classification of Diseases (ICD). The ICD update, which includes an extension code for ageing-related diseases, implies the recognition of ageing as a major disease risk factor. One of the most prominent longevity scientists, Dr David Sinclair, has developed and tested a theory of ageing. And while we haven't found the fountain of youth just as yet, Dr Sinclair believes we’re rather close.

Somehow we as a society have fallen into a pro-ageing trance…that we can age “gracefully” while being “healthy”. That ageing is inevitable, a natural course of life. But is it, really? One radical idea supported by science – that ageing is a root cause of many other chronic diseases, such as dementia, cancer and atherosclerosis – is yet to sink in. An even more radical idea – that ageing can not only be slowed down but indeed reversed – sounds like heresy, yet it’s already a reality, and not just in animals, but in humans too. One recent, and perhaps the first, clinical study on humans presents robust evidence that “regression of multiple aspects and biomarkers of aging is possible in man”. Enough to make you feel excited!

Why do people want to live long healthy lives?

I have my own motivations.

I don't like the alternative, I enjoy being alive! Life is amazing! There are so many places on this planet that I’m yet to see and so many different people, cultures and foods to experience.

I have a keen interest in technology and innovation. I teach and do academic research on these topics. I want to see how humans become a multi-planetary species, how we “drive” flying cars, whether there is life on Mars, and when cryptocurrencies become the native money of the internet. While I don’t completely buy into the idea of exponential growth of science and technology in the next 20-30 years, I would still absolutely love to witness all the brilliant new tech.

There are so many new things to learn. Human knowledge has become very complex and specialised, and yet to bring about new scientific breakthroughs we need to do away with knowledge silos in favour of inter-disciplinary thinking and capabilities. Although some lucky people on this planet are polymaths and can achieve depth of knowledge in multiple disciplines in a lifetime, I personally need more time to master new skills.

I want to create new things and touch the hearts and minds of many people. Write new books, develop new courses, create colourful mosaics and plant a Japanese garden from scratch…

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