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What Determines Life Expectancy? - Pt. 2

As people everywhere are living longer than ever before, scientists want to understand how and why we age? Their research has revealed that lifestyle— not just genetics — influences how long and how well we live.A sample of DNA is pipetted into a petri dish with a background of DNA gel.


Thestudy of ageing is a relatively young science. For most of history, it was assumed that ageing was unavoidable. It was only in the 1990s, that geneticist Thomas Johnson and colleagues studied a type of roundworm calledC. elegans (Caenorhabditis elegans) that showed variants in the worm's genetic code (DNA) mutations could influence lifespan.

This sparked more animal studies, confirming the role of genetics in lifespan and identifying more genes that, when mutated, could extend lifespan. The relevant genes are mainly related to cell maintenance and metabolism, like repairing damaged DNA, maintaining the ends of DNA strands (telomeres), and protecting against free radicals.

From there, research inevitably turned to humans —do we have similar ‘longevity genes?

Based on studies of long-lived people who looked forgenetic similarities, the answer appears to be,yes. Like other animals, mutations in human genes associated with cell maintenance and metabolism are essential to determining how long we live. More information onhuman longevity is being discovered each year.


Genetics is just one piece of the ageing puzzle.Research indicates that genetic factors can only account for about 25% of the variation in the human lifespan.Of course, this leaves most variation in our lifespan to non-genetic factors.

This new understanding challenges long-held assumptions about ageing. Scientists likeProfessor David Sinclair, an expert in ageing at Harvard Medical School, are making the case that ageing is not inevitable.

Key to our new understanding of ageing is the study of how our DNA is interpreted by our cells, called epigenetics. Like the genome, our epigenome is heritable; unlike the genome, it is changeable.

“If the genome were a computer, the epigenome would be the software. It instructs the newly divided cells on what type of cells they should be and what they should remain, sometimes for decades, as in the case of individual brain neurons and certain immune cells.

DAVID A. SINCLAIR, Lifespan: The Revolutionary Science of Why We Age – and Why We Don’t Have To

Epigenetic changes that affect cell metabolism or maintenance could explain why ageing patterns are different, even between identical twins. Epigenetic changes can be spontaneous or caused by factors like smoking or UV light.

According to Sinclair's Harvard research, epigenetic changes are key to ageing and they can be influenced by lifestyle interventions.

Okinawa woman elderly dancing in traditional clothing.

The remarkable growth inlife expectancy since the dawn of industrialisation shows clearly that how we live, plays a role in how long we live. Tobacco consumption, obesity, and inactivity are well understood as risk factors for disease, cutting short our lifespans and healthspans.

But what could help? Eating less frequently has been shown to cause epigenetic changes that delay ageing in mice, possibly due to the diversion of resources from cell reproduction to cell maintenance. It's feasible that areas likeOkinawa andSardinia Islands may owe their reputation for extreme longevity in part to their lower-calorie diets.

According to Sinclair, the most important lifestyle factor for slowing ageing is eating less frequently. While he does not advocate disordered eating — and scientists stress that we do not yet know how to reap the possible benefits ofdietary restrictions without negative side effects — he says:“I’m suggesting that three square meals a day is not optimal for longevity”.

Scientists are also identifying individual compounds that play a key role in the ageing process. For instance, declining levels of a compound calledNAD+ has widespread cellular effects and can trigger epigenetic changes associated with ageing, but can be compensated for with supplements.


What determines lifespan?

It’s complicated — and genetics, epigenetics and lifestyle play entangled roles in how long and how well we live. But, with genetics only accounting for a quarter of lifespan variability, most of us have more control over how long — and how well — we live than we might think.

Join us forPart 3, where we will learn more about what happens to our cells as we age.

The content of this article is for informational purposes only.
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