There are more people alive today above the age of 100, called centenarians, than ever before. The curious part of this tale is how healthy many of them are relative to their compatriots who did not live as long.
It is becoming clear that people who break through the 90-plus barrier represent a physical elite, markedly different from the elderly who typically die younger than them. Far from gaining a longer burden of disability, their extra years are often healthy ones. They have a remarkable ability to live through, delay or entirely escape a host of diseases that kill off most of their peers. Supercentenarians – people aged 110 or over – are even better examples of ageing gracefully.
Healthy is relative term for someone that old. In fact, very few people who live to be 100 are able to avoid certain chronic conditions entirely. Centenarians are divided into 3 categories regarding their health: delayers, survivors, and escapers.
Not all of the oldest old survive by delaying illness or disability, though – many soldier through it. Jessica Evert of Ohio State University in Columbus examined the medical histories of over 400 centenarians (The Journals of Gerontology Series A, vol 58, p 232). She found that those who achieve extreme longevity tend to fall into three categories. About 40 per cent were “delayers”, who avoided chronic diseases until after the age of 80. This “compression of morbidity”, where chronic illness and disability are squeezed into ever-shorter periods at the end of life, is a recent trend among ageing populations. Another 40 per cent were “survivors”, who suffered from chronic diseases before the age of 80 but lived longer to tell the tale. The final 20 per cent were “escapers”, who hit their century with no sign of the most common chronic diseases, including heart disease, cancer, diabetes, hypertension and stroke. Intriguingly, one-third of male centenarians were in this category, compared with only 15 per cent of women (see “Two paths to 100”).
There is conclusive evidence pointing to genetics as a contributing factor in such extreme longevity. Precisely how much is still being debated. Environmental factors like exercise and diet should not be dismissed even if some centenarian reports smoking 60 cigarettes a day for decades.
Scientists are working hard to uncover whatever genetic secrets are responsible for a long healthy life. Very little has been found to date.
Until recently, the only exception was ApoE, and in particular a variant of this gene known as e4, which bestows carriers with a much higher than average risk of developing Alzheimer’s and heart disease. Across the world, this unfortunate version of ApoE is about half as common in centenarians as in younger adults. Last year, a second promising candidate emerged – a variant of a gene called FOXO3A. At the University of Hawaii, a team led by Bradley Willcox, Craig’s identical twin, found that people who carried two copies of a particular form of the gene were almost three times as likely to make it to 100 than those without the variation, and also tended to start their journey into old age with better health and lower levels of stroke, heart disease and cancer (Proceedings of the National Academy of Sciences, vol 105, p 37). “There are so many false positives in this field that FOXO3A is very exciting,” says Bradley Willcox.
FOXO3A is involved in several signalling pathways that are conserved across animal species. It controls the insulin/IGF-1 pathway, which influences how our bodies process food. It also controls genes that protect cells from highly reactive oxygen radicals – molecules often thought to drive human ageing through the cumulative damage they wreak on DNA. FOXO3A could even protect against cancer by encouraging apoptosis, whereby compromised cells commit suicide. The variant of FOXO3A associated with longevity is much more prevalent in 100-year-olds even than in 95-year-olds, which clearly demonstrates the value of studying the centenarian genome.
As was discussed earlier in regards to Alzheimer’s disease, it is interesting to note that men who survive to be 100 are in better shape than women.
Men, meanwhile, have the double disadvantage of being both more prone to risky behaviours throughout their lives and more likely to succumb to chronic illnesses as they age. This means that men who do make it to their century must depend more on genetic trump cards to see them through.