Genes Become Increasingly Important in Extreme Old Age

The lesson to take away from the last fifteen years of study of the genetics of longevity is that genetic variation in humans is simply not all that important throughout most of life. Aging is caused by damage, and certainly during the period of life in which damage levels in cells and tissues are still comparatively low, all the way into early old age, the vast majority of genetic variants identified in our species have little to no effect on survival. Given that the best possible path forward to treat aging is to build treatments to periodically repair damage levels so as to keep them low, this tells me that the study of the genetics of longevity variance is not very important from a practical point of view, meaning from the standpoint of building new medical technologies to extend healthy life. It is the study of how extremely damaged biology works, and how normally unimportant genetic variants can suddenly become much more relevant to survival in frail individuals suffering advanced stages of the degeneration of aging. That is an interesting area of study, as is true of all biochemistry, but not a good focus if we want to see extended healthy life, more time spent alive with little accumulated damage.

When it comes to aging, damage, and repair, to a first approximation we are all the same. Treatments for repair of aging will be mass-manufactured once developed, exactly the same therapy for every individual: it will be the polar opposite of the often envisaged future of personalized medicine. The genetics of variations in the longevity of physically old people will become a historical curiosity, like the genetics of smallpox survival. Outside of narrow specialties in history and biochemistry we don't care as to how genetic variations influence smallpox survival, and rightly so. The research community found the means to eliminate the condition for everyone and the world moved on. This is an age in which genetics is the newest tool in the toolbox, the technologies suddenly cheap and capable, and it is being applied to everything. Hence the existence of ventures like Human Longevity, Inc. Genetic studies of aging won't provide a straightforward path to much greater healthy longevity, however, because - as noted - genetic variants are only important to the course of aging and disease in the old and the frail. Meaningful treatments for aging will be those that prevent people from ever being old and frail, or rescue them from that state, by repairing the damage that causes aging.

None of this is preventing considerable growth in the study of the genetics of longevity and aging in humans, of course. It is very much a part of the research mainstream. As more data accumulates, the present picture of genes and aging is refined to show that the increase in the relevance of genetic variants to survival in a damaged state just keeps on growing the further into extreme old age you go. The more damaged you are, the more your particular genetic quirks matter.

BU/BMC study finds the role of genes is greater with living to older ages

Genes appear to play a stronger role in longevity in people living to extreme older ages. The study found that for people who live to 90 years old, the chance of their siblings also reaching age 90 is relatively small - about 1.7 times greater than for the average person born around the same time. But for people who survive to age 95, the chance of a sibling living to the same age is 3.5 times greater - and for those who live to 100, the chance of a sibling reaching the same age grows to about nine times greater. At 105 years old, the chance that a sibling will attain the same age is 35 times greater than for people born around the same time - although the authors note that such extreme longevity among siblings is very rare. "These much higher relative chances of survival likely reflect different and more potent genetic contributions to the rarity of survival being studied, and strongly suggest that survival to age 90 and survival to age 105 are dramatically different phenotypes or conditions, with very different underlying genetic influences."

The study analyzed survival data of the families of 1,500 participants in the New England Centenarian Study, the largest study of centenarians and their family members in the world. Among those families, the research team looked at more than 1,900 sibling relationships that contained at least one person reaching the age of 90. The findings advance the idea that genes play "a stronger and stronger role in living to these more and more extreme ages," and that the combinations of longevity-enabling genes that help people survive to 95 years are likely different from those that help people reach the age of 105, who are about 1,000 times rarer in the population. For a long time, based upon twins' studies in the 1980s and early '90s, scholars have maintained that 20 to 30 percent of longevity or even life span is due to differences in genes, and that the remainder is due to differences in environment, health-related behaviors or chance events. But the oldest twins in those studies only got to their mid- to late-80's. Findings from this and other studies of much older (and rarer) individuals show that genetic makeup explains an increasingly greater portion of the variation in how old people live to be, especially for ages rarer than 100 years."

Comments

Very interesting. The idea that genetic variation does not influence aging until the end makes sense. After all, most of us live more than five decades in decent health, as our genetic repair mechanisms effectively do their jobs. This is regardless of whether we turn out to be supercentenarians or just an average life-spanner.

While specifically studying the genetic differences in longevity among individuals may not matter as you say, personalized medicine could still be useful in applying certain SENS technologies. It seems optimistic to assume every SENS procedures could be applied identically to everyone without accounting for their biological (including genetic) differences.

Posted by: bo at March 27th, 2015 1:40 AM

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