Why it remains a scientific mystery that some people can live more than 100 years

A 35-year-old man has only a 1.5% chance of dying in his next 10 years; the same man at 75 has a 45% chance of dying before reaching 85.

Clearly, aging is bad for our health. But if we look on the bright side, we have made great progress in understanding the fundamental mechanisms that control aging and old-age-related diseases.

Several closely linked biological processes, sometimes called “hallmarks of aging,” including our supply of stem cells and communication between cells, act to keep us healthy in the early part of our lives. Problems arise when they start to fail.

Clinical trials are currently underway to see if targeting some of these hallmarks can help improve age-related conditions, such as diabetic kidney disease, aspects of immune function, and pulmonary fibrosis, among others. So far so good.

But unfortunately, big unanswered questions remain in the biology of aging.

To assess what they are and how to address them, the American Federation for Aging Research (AFAR), a charity, recently convened a series of meetings with leading scientists and physicians in the area.

The experts agreed that it is key to understand what is special about the biology of humans who live more than a century.

Centenarians make up less than 0.02% of the UK population, but have exceeded the life expectancy of their peers by almost 50 years (babies born in the 1920s had on average a life expectancy of less than 55 years). How they did it?

The children of centenarians are healthier

We know that centenarians live so long because they are exceptionally healthy.

They are in good health for about 30 years longer than most normal people, and when they finally do get sick, they are only so for a very short time.

This “compression of morbidity” is clearly good for them, but it also benefits society as a whole.

In the United States, the health care costs of a person who is 100 years or older during the last two years of life are approximately a third of those of someone who dies at 70 (a time when most centenarians don’t even need to see a doctor).

The children of centenarians are also much healthier than average, indicating that they are inheriting something beneficial from their parents. But is this genetic or relative to the environment?

Centenarians aren’t always careful about their health

Are centenarians the model for a healthy lifestyle?

Among the general population, watch your weight, do not smoke, drink moderately And eating at least five servings of fruits and vegetables a day can increase life expectancy by up to 14 years compared to someone who does none of these things.

This difference is greater than that observed between the inhabitants of the most and least disadvantaged areas of the United Kingdom, so, intuitively, one would expect it to play a role when it comes to living for more than a century.

But surprisingly, this doesn’t have to be the case.

One study found that close to 60% of Ashkenazi Jews over 100 years old have smoked heavily For most of their lives, half are overweight for the same length of time, less than half exercise frequently, and less than 3% are vegetarian.

The children of people who live 100 years or more also appear to be more careful about their health than the general population.

However, compared to their peers who eat the same type of food and have the same level of wealth and body weight, centenarians have half the prevalence rate of cardiovascular disease.

There is something innately exceptional about these people.

The big secret

Could it be due to special genetics? If so, there are two ways it could work.

Centenarians may carry unusual genetic variants that prolong life or may instead lack other more common that cause diseases and disorders in old age.

Several studies, including our own work, have shown that centenarians have as many bad genetic variants as the general population.

Some even carry two copies of the largest common risk gene known to surround Alzheimer’s disease (APOE4), but they still don’t get the disease.

So a plausible working hypothesis is that centenarians have beneficial and rare genetic variations rather than lacking the ones that cause disadvantages. The best available data support this hypothesis.

More than 60% of centenarians have genetic changes that alter genes that regulate growth in early life.

This implies that these people are human examples of a type of life extension observed in other species.

Growth hormone

Most people know that small dogs tend to live longer than large dogs, but few believe that it is a widespread phenomenon throughout the animal kingdom.

Ponies can live longer than horses, and many lab mice with dwarf mutations live longer than their larger pairs.

One possible cause for this is lowered levels of a growth hormone called IGF-1, although century-old humans are not necessarily lower than the rest of us.

Obviously, growth hormone is needed early in life, but there is increasing evidence that high IGF-1 levels in adulthood or old age are associated with an increase in disease during old age.

The detailed mechanisms around this remain an open question, but even among centenarians, women with the lowest levels of growth hormone live longer than those with the highest levels. They also have better cognitive and muscle function.

However, that does not clarify the doubt. Centenarians are different from the rest of us in other ways, too. For example, they tend to have good cholesterol levels, which suggests that there may be a number of reasons for their longevity.

Ultimately, centenarians are “natural experiments“that show us that it is possible to live in excellent health even if not so good genes have been passed on to you or even if you choose not to pay attention to health-related messages. The important thing is to have rare and now understood mutations little.

Understanding exactly how this works should allow scientists to develop new drugs or interventions for biological processes in the right tissues at the right time.

If this becomes a reality, perhaps more of us can move on to the next century.

But, until then, don’t take the healthy lifestyle advice of 100-year-olds.

* Richard Faragher is Professor of Biogerontology at the University of Brighton and Nir Barzilai is Professor of Medicine and Genetics at the Albert Einstein College of Medicine.

Read the original article here.

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