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R&D breakthroughs tackle the nine hallmarks of ageing – Interview

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In 2013, researchers identified nine areas of the body’s cells that drive ageing. Over the past decade, billions have been spent trying to target these “nine hallmarks” with interventions to extend healthspan, resulting in many R&D breakthroughs, from senolytics to biological clock measurement.
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Greg Macpherson, pharmacist and founder of New Zealand-based Science Research Wellness (SRW) Laboratories, will be giving an overview of the pathways and supplements that can support healthy ageing at Vitafoods Virtual Expo Europe, which runs from 14-17 November. We caught up with him ahead of the event to find out more.

What does healthy ageing mean?

“A common description of ageing is ‘the time-dependent functional decline that affects living organisms’. From a human perspective, healthy ageing is simply going through the process in the absence of disease and discomfort – a period of our lives often referred to as healthspan – for as long as possible.

“In the past, achieving healthy ageing was down to equal parts of luck and good genes. We now know that through healthy lifestyle habits – such as following a plant-based diet, getting adequate exercise, taking time for regular relaxation, focusing on good sleep, and avoiding toxins – we create a positive environment for our cells that will compound over a lifetime to extend healthspan.

“These factors, plus a focus on a preventative maintenance strategy involving regular well-checks, occasionally placing our bodies in stress – fasting, [high intensity interval training] HIIT, cold and hot exposure – and taking evidence-based supplements, can extend the amount of time we spend in good health.”

What are the nine hallmarks of ageing, and how can they be harnessed?

“The hallmarks of ageing are drivers or causes of cellular ageing. Each hallmark has three things in common: they change naturally over time. If you experimentally aggravate them, it accelerates ageing; conversely, if you experimentally ameliorate them, it slows down ageing. Currently there is a consensus that there are nine hallmarks but this list is likely to be extended.

“The nine hallmarks include genomic instability, telomere attrition, epigenetic alteration, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Their identification is an exciting advance because it gives researchers nine targets to harness to modulate the ageing process. Already, we have seen the benefits of this work as researchers develop senolytics to lower the burden of senescent cells in our bodies as we age, target mitochondria to reverse mitochondrial dysfunction, and unpack the benefits of modulating the key nutrient-sensing protein, mTOR, for extended lifespan.”

Which pathways or supplements can be used to support healthy ageing?

“To date, the most effective intervention to support healthspan extension is calorie restriction. The primary pathway involved in this process is the inhibition of a protein called mTOR. The most well-known compound to inhibit mTOR is rapamycin, which has increased lifespan in every organism that it has been tested on. Human studies are under way.

“A number of supplements interact with mTOR, including withaferin A, a component of ashwagandha, and AMPK-activating compounds that indirectly modulate mTOR.

“Other strategies to support healthy ageing are to top up key molecules involved in cellular processes that decline as we age. One of the most well known of these is [nicotinamide adenine dinucleotide] NAD, the most abundant molecule in our cells after water. Levels of this vital molecule decline significantly from our late thirties, and research shows that supplementing with NAD precursors like [nicotinamide mononucleotide] NMN and [nicotinamide riboside] NR has a significant cellular benefit.”

What are the latest novel developments in healthy ageing R&D?

“Developments showing the greatest potential to extend healthy ageing include senolytics and the development of biological clock measurement.

“Senolytics are a class of supplements and medicines that target senescent cells. Senescent cells are cells that have either reached the end of their life, or have been shifted into a non-replicating mode because their role is complete, or something has gone wrong with them. Senescent cells secrete inflammatory molecules in an attempt to attract the immune system to remove and recycle them.

“However, as we age, the number of senescent cells overwhelms the ability of the immune system to remove them, causing the level of inflammatory molecules in the body to increase, with the downstream effect over time of disease and cellular stress. Research has shown that lowering the number of senescent cells in the body has a significant beneficial effect.

“Biological clock measurement is a breakthrough because, for the first time, we can measure the impact of interventions for their effect on our cellular age. The development of this technology will enable faster identification of compounds that have a positive effect on cellular health.”

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