And do it with food, not expensive pharma medicines

Investors in biotech companies are putting billions into a new category of drugs that promise to extend the number of years you can stay healthy – and improve the quality of life in later years.

Dr Richard Miller is a leading gerontologist at the University of Michigan. In an article in New Scientist headed ‘The Age of Living Younger’, he states:

“We have proven you can slow the ageing process using drugs”.

He’s right. But Big Pharma’s expensive drugs are not the only – or even the best way. Because you can get the same result with nutrition and food.

Why does so much illness appear age-related?

The incidence of almost every debilitating chronic disease – heart disease, stroke, dementia, cancer, arthritis, vision impairment – increases suddenly around the age of 60.

But it is not related to the passing of years. It is related to accumulated, unrepaired damage to DNA and to the cells that make up our tissues and organs – causing those organs to gradually fail. The damage accumulates because the body’s cell repair mechanisms stop working properly. Prevent, limit or even reverse that damage, by boosting cell repair mechanisms, and you stay healthier for longer. But how?

Toxic dead ‘zombie’ cells need to be cleared

The trillions of cells in your body are continually turning over. They replicate and ultimately die. Indeed, an estimated 50 billion die each day!  A normal cell death occurs through a process called apoptosis, and those dead cells are usually cleared away.

But occasionally the dead cells or debris from the dead cells is not cleared away. These are called senescent cells – cells that have suffered irreversible damage, but which have not been eliminated from the body.

Scientists sometimes refer to them as them junk or zombie cells.

Very recent research by Judith Campisi at the Buck Institute for Ageing shows that these senescent cells secret a cocktail of damaging chemicals that poison surrounding tissues and cause chronic inflammation.

We know inflammation underlies almost all age-related diseases and the Buck Institute explains how that inflammation occurs and directly links senescent cells to ageing itself and to cancer.

Lynne Cox, a biochemist at Oxford University, underlines the threat: “Senescent cells are very bad for you – they destroy the tissues around them”.

Even a small number of uncleared senescent cells trigger problems – just as a rotten strawberry in a punnet can cause the rest to go bad.

(Hold that analogy in your mind, as it will have special significance as we unravel this latest science).

The huge cost of senescent cells

A result of this damaging sequence – senescent cells poison surrounding tissues, which causes chronic inflammation, which causes multiple later life illnesses – is that the average person will live the last 12 – 18 years of their life with some sort of health issue and increasingly on medication.

This is not only distressing for the individual, but a huge cost for society. 80% of healthcare costs in the US are linked to later-life degenerative disease! It’s similar in the UK where the annual spend on healthcare is £2,892 for every man, women and child and most of that is spent on later life.

So, a drug that clears senescent cells and therefore extends healthy life span could literally save trillions.

You are likely to live a somewhat longer life – say typically to around 90
– but, importantly, stay healthy, vigorous and productive until your final year or two. As one researcher put it, perhaps too bluntly,

“We are not trying to fill care homes with geriatrics, we are trying to make sure you live actively and well to enjoy your pension to the full!”

You can see why bio-tech investors are so excited. But our interest is in doing this without Big Pharma’s expensive, patented pills.

How you can clear away senescent “zombie” cells

If you take senescent cells from an old mouse and transplant them into a young mouse, it ages prematurely and suffers age-related diseases.

The reverse is true. In 2011 researchers at the Mayo Clinic used a drug to clear senescent cells from aged mice – and it significantly extended the time they were disease-free and enabled them to function as young mice.

Removing senescent cells “jump starts tissues’ natural repair mechanisms” as a Johns Hopkins researcher puts it.

Other studies in 2016 and 2018, including at Newcastle University, showed that a range of illnesses – from simple frailty to heart disease to osteoporosis to dementia and even to osteoarthritis – was halted or even reversed by clearing senescent cells.

As a leading researcher put it, we are now seeing:

“ … how multiple diseases of ageing are being caused buy a single underlying cause”.

It is a genuine breakthrough in understanding how healthy lifespan can be extended.

James Pickett, is head of research at the Alzheimer’s Society, and was not involved in the Mayo study. His comment:

“There hasn’t been a new dementia drug in 15 years, so it’s exciting to see the results of this promising study.”

The importance of “senolytics”

So how do we clear away senescent cells?  The answer is with senolytics – defined as molecules that seek out, destroy and eliminate senescent cells.

There are drugs that do this – like dasatinib, navitoclax and possibly the diabetes drug metformin – but none appears to work very well on their own, without being coupled with flavonoids.

Flavonoids are a class of nutrients in fruits and vegetables that are as important to health as the vitamins and minerals that fruits and veggies also provide.

They include the pigments in plants – like resveratrol (found in grape skin, red wine, blueberries and bilberries), quercetin (found in red onions, apples, green and black tea and grapes), beta carotene, lutein and lycopene (the red pigment found in tomatoes).

Many flavonoids are linked to an anti-cancer effect, as well as being senolytic.

A flavonoid with powerful senolytic action – fisetin

But the most powerful flavonoid with senolytic activity appears to be a little-known pigment called fisetin – found in strawberries – at a level that’s 6 times higher than in the next fruit, which is apples.

A lead researcher at the Institute on the Biology of Ageing and Metabolism at the University of Minnesota told Newsweek magazine:

“We’re looking for drugs that can kill these damaged senescent cells that are very toxic to our bodies and accumulate as we get older. It turns out that fisetin is a natural product that we were able to show very selectively and effectively kills these senescent cells.”

You’ll note that she didn’t suggest you just loaded up with strawberries. Unfortunately the default reaction from most researchers is to make a natural product into a drug!!

Another proven senolytic – nicotinamide form of Vit B3

Another proven senolytic is nicotinamide, a form of vitamin B3, which unlike niacin, does not cause flushing.  Nicotinamide creates a blood chemical called NAD+, which clears DNA damage from especially mitochondrial cells – the tiny ‘energy factories’ in our cells. That should, in turn, improve energy levels.

There are already supplements on the market that combine resveratrol, quercitin and nicotinamide. But they are jumping the gun. Partly because research on quercetin and resveratrol as senolytics, on their own, is not conclusive. And partly because senolytics are not the whole story.

All-round cellular spring cleaning

To create a truly comprehensive plan that will clear senescent cells and therefore prolong health, we need to include what are called mTOR inhibitors. O.K. it’s a mouthful – but stay with me!

The mTOR pathway

mTOR is a pathway within your cells that regulates the life cycle of that cell – its growth, repair and natural death. The science is rather complicated, but the key is this.

• mTOR senses your nutrient intake and when it senses adequate nutrients, the cell will replicate.  
• When it is suppressed, then rather than replicating, the cell goes into repair mode.
• When it is over-stimulated it can promote excess growth and even tumours.

So it’s a finely balanced cycle. And sometimes you’ll want to suppress or down-regulate mTOR to ensure your cell repair mechanisms are working properly.

One way to suppress mTOR is calorie restriction, which we know improves cell repair and makes organisms live longer. Which is why some people fast. But starving yourself is hardly the most attractive way to live longer!

Down-regulating mTOR to up-regulate cell repair

The key fact to remember is that to upregulate cell repair – thereby boosting health and longevity – you need to down-regulate or damp down the mTOR pathway.

Assuming fasting is not your option, there are drugs that do this – possibly including metformin. Exercise also helps suppress the mTOR pathway. But again, certain nutrients and food compounds do it.

So why risk the drugs?

Some of the most powerful, natural, mTOR inhibitors include curcumin, EGCG (an ingredient in green tea), Omega 3, olive oil, indoles (a compound in broccoli, sprouts and kale), genistein (a compound in soy with anti-cancer credentials), grapeseed extract, fisetin (again) and quercetin.

You should note that there are also factors that can dangerously over-stimulate the mTOR pathway, notably excess protein. This makes sense – if mTOR senses excess nutrition intake, it may go into cell replication overdrive and cancer is marked by unrestricted cell replication.

Garbage disposal for old cells

The final piece of the jigsaw is that down-regulated mTOR also cleans out dead cell debris, a process called autophagy – which literally means “self-eating”.

So, although senolytic activity and autophagy are not exactly the same, you want both of them working properly to do a frequent ‘internal spring clean’. Or as one researcher puts it – “to act like a garbage disposal system for old cells”.

The summary so far

• Cleaning out senescent cells that are dead, but still present in the body, prevents them causing toxicity which leads to inflammation and thus to many diseases that are related to age, but not caused by ageing. That includes osteoarthritis, cancer and Alzheimer’s.
• Damping down mTOR activity encourages the process of cell repair, which otherwise becomes weaker over time. It also ensures that ‘zombie’ cells are cleared away.
• You can liken both processes – which are vital for reducing the risk of cancer, heart disease, dementia and even arthritis, and for increasing the years in which you remain healthy – to a regular spring clean.
• There are natural compounds that do this – including nicotinamide (vitamin B3), the flavonoids in strawberries, blueberries, turmeric (curcumin), green tea, grapeseed, green leafy vegetables, onions and garlic.

What you can do with supplements

I need to make a disclosure at this point.

I have been researching nutrition and health for over 30 years. Some years ago, when I was 60, I worked with the then Chair of the Forum on Food and Health at the Royal Society of Medicine, Dr Paul Clayton, to create a comprehensive health food supplement.  Because we knew from many surveys that a simple vitamin and mineral pill made little difference.

The multi-capsule daily health food supplement is called NutriShield.

• It is high in antioxidants and anti-inflammatory nutrients, because we knew that oxidative free radical damage and inflammation were key causes of chronic age-related illness.
• It includes nutrients known to boost the immune system as we know immune function can decline with age.
• It includes nutrients that help express or ‘turn on’ genes that lead to improved health – nutrients like lutein, betaine, omega 3, folate (folic acid), genistein, curcumin and beta carotene.
• NutriShield also includes high levels of flavonoids and key vitamins and minerals – levels found in the diets of longevity hot-spots around the world called blue zones. But these levels are hard to achieve in a typical Western diet.

It’s only recently that the importance of clearing out toxic senescent cells has been uncovered.

However, we knew about the need to down-regulate mTOR and already had many of the mTOR down-regulators in NutriShield – nutrients like curcumin, green tea, genistein, Omega 3 and grapeseed.

We included high levels of flavonoids (and nicotinamide) because they are found diets of people who stay healthy the longest. We now know they are also senolytics. The potency of fisetin as a senolytic has only recently come to prominence, so it is not yet included in NutriShield.

Add strawberries every 2 weeks

An encouraging thing from the senolytic research is that it appears you don’t need to take action every day – an occasional, probably bi-weekly, clear-out seems to work very well.

So why not add a large bowl of strawberries at least once every two weeks? That’s certainly no hardship for most people! And canned or frozen are fine out of season.

Try this healthy eating plan – it’s simple and effective

Finally, there is a PDF of a healthy eating plan you can download here.

It combines the best health and nutrition advice from amongst others, Harvard Health, UCLA, University College London and the American Cancer society.

The combination of NutriShield and the eating plan will tackle those zombie cells too!

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This article was written by Colin Rose, a Senior Associate Member of the Royal Society of Medicine, who has been writing on science for 40 years.

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Dr Paul Clayton designed NutriShield as a comprehensive health supplement with OPTIMUM levels of essential nutrients. See more detail elsewhere on this site or click on the button.

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Dr Paul Clayton’s best-selling book Health Defence is available from booksellers.

Read it here online or see the website www.healthdefence.com for excerpts and links to buy direct from the publisher.

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See online here for delicious recipes from the Health Defence Cookbook incorporating healthy foods featuring in a Mediterranean Diet.

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References:

Cellular Senescence: The Sought or the Unwanted? ; Sun, Y., Coppé, J. P., & Lam, E. W. F. Trends in Molecular Medicine. (2018).

Senescence in health and disease. He S, Sharpless NE. Cell. 2017; 169: 1000-1011

Cellular senescence and its effector programs. Salama R. et al; Genes Dev. 2014; 28: 99-114

New agents that target senescent cells: the flavone, fisetin, and the BCL-X_L inhibitors, Yi Zhu, et al, Aging (Albany NY) 2017

Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Gomes AP et al, Cell. 2013 Dec 19;155(7):1624-38. doi: 10.1016/j.cell.2013.11.037.

It is time to classify biological aging as a disease Sven Bulterijs, et al; Frontiers in Genetics 2015

Inhibition of PI3K/Akt/mTOR Signaling by Natural Products Shile Huang^*Anticancer Agents Med Chem. 2013 Sep; 13(7): 967–970.

Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor; Coppé, J. P., et al  (2008). PLoS Biology, 6(12), e301.

The senescence-associated secretory phenotype: the dark side of tumor suppression. Coppé, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). Annual Review of Pathological Mechanical Disease, 5, 99-118.

Autophagy and signaling: their role in cell survival and cell death. Codogno, P. and Meijer, A. J. (2005). Cell Death Differ. 12 Suppl. 2, 1509-1518.

Defining the Role of mTOR in Cancer; Guertin, D. A. and Sabatini, D. M. (2007). Cancer Cell 12, 9-22.

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