Nehaveigur

In Why We Die, Venki Ramakrishnan looks at longevity, and whether there may be a way to extend it.

I’ve talked with Ramakrishnan a few times when I did my PhD at the same Institute where he solved the structure of the ribosome. Remembering those conversations, it occurs to me that is the ideal person to write this book: He is obviously knowledgeable about the science, he communicates clearly, and he approaches complex questions with a humility that is rare for someone so accomplished. He also has the advantage that he can speak freely: As far as I know, he has no commercial interest in the lifespan extension industry.

Antagonistic Pleiotropy

One question he addresses is why we age at all. From the perspective of evolutionary theory, the likely answer is antagonistic pleiotropy:

The biologist George Williams suggested that aging occurs because nature selects for genetic variants, even if they are deleterious later in life, because they are beneficial at an earlier stage. This theory is called antagonistic pleiotropy […] Exactly as those theories would predict, mutations that increase life span reduce fecundity [in fruit flies and worms]

I’d add that it’s not only that those variants are selected by nature, but also in many cases that they’re not selected against.

In many animals such as worms, there are mutations that dramatically increase lifespan, supporting antagonistic pleiotropy as an explanation for why we die.

Mutations that affect longevity dramatically might seem to suggest that aging is under the control of a genetic program. This idea might seem to contradict evolutionary theories of aging, but, in fact, it doesn’t. When worms were subjected to alternative cycles of food and scarcity, it turned out that the long-lived mutant worms simply could not compete reproductively with shorter-lived, wild-type worms. These pathways allow organisms to have more offspring at the cost of shortening life later on, exactly as one might predict from the antagonistic pleiotropy or disposable soma theories of the evolution of aging.

Why does menopause exist? It’s a related question:

The increase in our life span over the last century brings us to another curious feature of aging that is almost unique to humans: menopause. With the exception of a few other species, including killer whales, most female animals can reproduce almost to the end of their lives, whereas women suddenly lose the ability in midlife. The abruptness of this change in women, as opposed to a more gradual decline in male fertility, is also strange […] Perhaps the real question is not why menopause occurs so early in life but why women live so long afterward […] perhaps menopause developed as an adaptation to maximize the chances of a woman’s children growing up – and this propagating her genes. This is the so-called good mother hypothesis […] The grandmother hypothesis for the origin of menopause takes the idea one generation further […] It could also simply be that the number of eggs in a female evolved to match its average life span in the wild […] perhaps there has just not been enough time for the aging human ovaries to adapt to that increased lifespan

The Limits of Longevity

Another question Ramakrishnan tackles is what the upper limit to human lifespan may be. The record holder for longest life is Jeanne Calment, who died at the age of 122 in 1997.

We have almost doubled life expectancy in the last hundred years, but we have done nothing at all to increase the maximum human life span, which remains about 120 years […] For most of human history, life expectancy was just over thirty. But today, in developed countries, we can look forward to living to our mid-eighties […] The science writer Steven Johnson makes the point that this is like each of us acquiring an entire additional life […] Most of the increase in life expectancy has come about because of improvements in public health rather than groundbreaking advances in medicine. Johnson observes that the three biggest contributors have been modern sanitation and vaccines, which both prevented the spread of infection, and artificial fertilizers.

Personally, I’m skeptical about attempts to increasing our life span beyond 120 being successful anytime soon. If there was a single mutation that increases human life span like the ones we have discovered for worms, we’d probably have come across it already among the 8 billion people on Earth. This suggests that any medical intervention that has a chance of increasing our maximum life span would have to be quite complex. Interventions that increase the average lifespan and bring it closer to the maximum lifespan seem more realistic in the near term.

Even curing all forms of cancer would add only four to five years on average […] Eliminating all aging-related causes of death would not increase life expectancy by more than fifteen years.

And this:

While many centenarians live extraordinarily long lives in good health, about 40 percent of them had  an age-related disease prior to 80. By contrast, supercentenarians [those that reach 110 years of age] are healthy nearly their entire lives. As they approached the limit of the human life span at around 120 years, like the one-hoss-shay they experienced a rapid terminal decline in function and died.