Extending Life: The Five Most Promising Methods – So Far

Extending Life: The Five Most Promising Methods – So Far

Most people want to live a long and happy life – or at least avoid a short and miserable one. If you’re in that majority, then you’re in luck. Over the last decade, a quiet research revolution has occurred in our understanding of the biology of aging. [1] The challenge is to turn this knowledge into advice and treatments we can benefit from. Here we bust the myth that lengthening healthy life expectancy is science fiction, and show that extending life is instead scientific fact.

1. Nutrition and lifestyle

There’s plenty of evidence for the benefits of doing the boring stuff, such as eating right. A study of large groups of ordinary people show that keeping the weight off, not smoking, restricting alcohol to moderate amounts and eating at least five servings of fruit and vegetable a day can increase your life expectancy by seven to 14 years compared with someone who smokes, drinks too much and is overweight. [2]

Cutting down calories even more – by about a third, so-called dietary restriction – improves health and extends life in mice and monkeys, as long as they eat the right stuff. However, that’s a tough ask for people constantly exposed to food temptation. The less extreme versions of time-restricted or intermittent fasting – only eating during an eight-hour window each day, or fasting for two days every week – is thought to reduce the risk of middle-aged people getting age-related diseases. [3]

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2. Physical activity

You can’t outrun a bad diet, but that doesn’t mean that exercise does not do good things. Globally, inactivity directly causes roughly 10% of all premature deaths from chronic diseases, such as coronary heart disease, type 2 diabetes and various cancers. [4] If everyone on Earth got enough exercise tomorrow, the effect would probably be to increase healthy human life expectancy by almost a year.

But how much exercise is optimal? Very high levels are actually bad for you, not simply in terms of torn muscles or sprained ligaments. It can suppress the immune system and increase the risk of upper respiratory illness. [5] Just over 30 minutes a day of moderate to vigorous physical activity is enough for most people. [6] Not only does that make you stronger and fitter, it has been shown to reduce harmful inflammation and even improve mood. [7]

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3. Boosting the immune system

However fit you are and well you eat, your immune system will, unfortunately, get less effective as you get older. Poor responses to vaccination and an inability to fight infection are consequences of this “immunosenescence”. It all starts to go downhill in early adulthood when the thymus – a bowtie-shaped organ in your throat – starts to wither.

That sounds bad, but it’s even more alarming when you realize that the thymus is where immune agents called T cells learn to fight infections. Closing such a major education center for T cells means that they can’t learn to recognize new infections or fight off cancer effectively in older people.

You can help – a bit – by making sure you have enough key vitamins, especially A and D. A promising area of research is looking at signals that the body sends to help make more immune cells, particularly a molecule called IL-7. We may soon be able to produce drugs that contain this molecule, potentially boosting the immune system in older people. [8] Another approach uses the food supplement spermidine to trigger immune cells to clear out their internal garbage, such as damaged proteins. This improves the elderly immune system so much that it’s now being tested as a way of getting better responses to COVID vaccines in older people. [9]

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4. Extending Life by Rejuvenating cells

Senescence is a toxic state that cells enter into as we get older. It wreaks havoc across the body, generating chronic low-grade inflammation and disease. In other words, it essentially causes biological aging.

In 2009, scientists showed that middle-aged mice live longer and stay healthier if given small amounts of a drug called rapamycin. [10] Rapamycin inhibits a key protein called mTOR that helps regulate cells’ response to nutrients, stress, hormones and damage.

In the lab, drugs like rapamycin (called mTOR inhibitors) make senescent (aged) human cells look and behave like their younger selves. [11] It is still too early to prescribe these drugs for general use. However, a new clinical trial has just been set up to test whether low-dose rapamycin can really slow down aging in people. [12]

Discovered in the soil of Easter Island, Chile, rapamycin carries with it significant mystique and has been hailed in the popular press as a possible “elixir of youth”. It can even improve the memory of mice with dementia-like disease. [13]

But all drugs come with pros and cons – and as too much rapamycin suppresses the immune system, many doctors are averse to even consider it to stave off age-related diseases. However, the dose is critical and newer drugs such as RTB101 that work in a similar way to rapamycin support the immune system in older people, and can even reduce COVID infection rates and severity. [14]

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5. Clearing out old cells

Completely getting rid of senescent cells is another promising way forward. A growing number of lab studies in mice using drugs to kill senescent cells – so-called “senolytics” – show overall improvements in health. Additionally, as the mice aren’t dying of disease, they end up living longer too. [15]

Removing senescent cells also helps people. In a small clinical trial, people with severe lung fibrosis reported better overall function, including how far and fast they could walk, after they had been treated with senolytic drugs. [16] But this is only the tip of the iceberg. Diabetes and obesity, as well as infection with some bacteria and viruses, can lead to more senescent cells forming. Senescent cells also make the lungs more susceptible to COVID infection, and COVID makes more cells become senescent. [17] Importantly, getting rid of senescent cells in old mice helps them to survive COVID infection. [18]

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Aging and infection are a two-way street. Older people get more infectious diseases as their immune systems start to run out of steam. Coincidentally, infection drives faster aging through senescence. As such, aging and senescence are inextricably linked with both chronic and infectious diseases in older people. Therfore, treating senescence is likely to improve health across the board; consequently, extending life.

It is exciting that some of these new treatments for extending life are already looking good in clinical trials and may be available to us all soon.

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References

1. Is 150 years really the limit of human life span?
2. Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study
3. Intermittent and periodic fasting, longevity and disease
4. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy
5. Infectious episodes in runners before and after the Los Angeles Marathon
6. Healthy lifestyle and life expectancy free of cancer, cardiovascular disease, and type 2 diabetes: prospective cohort study
7. Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood
8. Harnessing the biology of IL-7 for therapeutic application
9. Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses.
10. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
11. Reversal of phenotypes of cellular senescence by pan-mTOR inhibition
12. Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL)
13. Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer’s Disease
14. Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials
15. Senolytic therapies for healthy longevity
16. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study
17. Senolytics reduce coronavirus-related mortality in old mice
18. Targeting aging cells improves survival