For most of human history we have conceived age as rigid — and ageing as inevitable. Now, a fresh understanding of the biological processes associated with ageing calls for us to challenge these assumptions.
Here are three areas of research that could change the way we think about ageing.
1. CHRONOLOGICAL AGE VS BIOLOGICAL AGE
Age has always been thought of as the length of time we have lived. But we are increasingly recognising age as something more complex, of which this traditional idea of age — ‘chronological age’ — is just one aspect.
A better measure of how old we are is our‘biological age’, which is based on damage accumulated by the body that restricts physical and mental capabilities and eventually causes systems to fail. There are a variety of indicators of biological age, including changes to our DNA —both the length of the protective ends (our telomeres, which affect how quickly cells age) and the biomarkers that control how our DNA is read (our epigenome).
Chronological age is not something over which we have any control
— but biological age is.
The factors that affect biological age include chronological age, genetics, nutrition and lifestyle. A 40-year-old smoker with a sedentary lifestyle can expect to have a more advanced biological age than their non-smoking, physically active twin, despite them sharing a chronological age. People who maintain a lower biological age are at lower risk of disease and may expect to enjoy both a longer lifespan and healthspan (life lived free from disease or disability).
Indeed, chronological age is how old we technically 'should be', but biological age is how old we actually are.
2. INCREASING HEALTHSPAN
Healthspan is influenced by interlinked factors including genetics, disease, environment, and lifestyle. Healthspan is influenced by interlinked factors including genetics, disease, environment, and lifestyle.
Many lifestyle interventions to extend healthspan are well understood (an article in Frontiers illustrates the improvements to healthspan), such as not smoking and taking regular exercise.
But there is also a growing body of research into what happens in our cells as we age, presenting new opportunities to alter our healthspan. There's lots of excitement around maintaining levels of NAD+, a molecule that plays a critical role in cell metabolism and which dramatically declines with age. A2018 study found that subjects whose diet was supplemented with a NAD precursor saw increased healthspan, whileolder subjects showed improved cognitive function when given the supplement for just two weeks. Harvard University geneticist and longevity expertProfessor David Sinclair believes NAD supplements may also slow ageing in humans, as noted in an anti-ageing article inHarvard Magazine.
Researchers continue to identify molecules associated with ageing, and explore whether they could be targeted to extend lifespan and healthspan. For instance, supplements like glutathione or glyNAC — antioxidants found in cells, which decline with age — have been shown to increase the lifespan in research studies.
Replicating these effects in humans could challenge our long-held ideas about the inevitability of physical and mental decline.
3. SENOLYTICS
A major biological process associated with ageing iscellular senescence: when cells can no longer perform cellular functions or replicate, but also do not die.This is an important process for protecting againstcancer and organ failure, but these ‘zombie’ cells can also emit a toxic chemical cocktail which causes damage to surrounding healthy cells. Increased cellular senescence is a biomarker of ageing.
Researchers are exploring whether this process could be combatted by reserving or suppressing senescence, or by killing senescent cells so they can be safely recycled by the body. 
Senescence is triggered in a cell once its telomeres — which shorten slightly with each cell division — fall below a certain size.
Therefore, there is considerable interest in whethertelomere extension could combat cellular senescence. This has been demonstrated at Stanford Medical University withcultured human cells.
Another approach to combating cellular senescence is senolytics — developing molecules that kill senescent cells. Senolytics tested so far include the cancer drug dasatinib and the flavonoidsquercetin and fisetin, and studies have shown increased lifespan and healthspan in subjects treated withsenolytics
Early evidence suggests that senolytics could also reduce the number of senescent cells in humans, an important step towards understanding if and how senolytics could work in the future. (Read more about the first evidence that senolytics are effective at decreasing senescent cells in humans.)
Ageing is a wildly complex process — a process we have only just begun to comprehend. These are just three of the many areas researchers are pursuing in their bid to help us age slower and more healthily.
Join us in Part 2 where we will further examine what determines life expectancy.
FAQS
What is NAD in medical terms?
Nicotinamide Adenine Dinucleotide, or NAD, was discovered in 1906 and is a coenzyme found in all living cells.NAD exists in two forms: NADH which helps improve brain functions such as concentration, memory, and alertness and NAD+ which maintains our neurological system and healthy internal organs.
What is quercetin?
Quercetin is a plant flavonoid found in onions, apples, kale, broccoli, green tea and coffee. As our bodies do not naturally produce it we can ensure that we get an adequate amount by taking a supplement.
What is quercetin used for?
Quercetin is powerful antioxidant, it plays a key role in removing senescent cells that contribute to ageing and age-related diseases.
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