2017 : WHAT SCIENTIFIC TERM OR CONCEPT OUGHT TO BE MORE WIDELY KNOWN?

Emeritus Professor of Physics and Astronomy, UC-Irvine; Novelist, Shipstar
Antagonistic Pleiotropy

Aging comes from evolution. It isn’t a bug or a feature of life; it’s an inevitable side effect.

Exactly why evolution favors aging is controversial, but plainly it does; all creatures die. It’s not a curse from God or imposed by limited natural resources. Aging arises from favoring short-term benefits, mostly early reproduction, over long-term survival, when reproduction has stopped.

Thermodynamics doesn’t demand senescence, though early thinkers imagined it did. Similarly, generic damage or "wear and tear" theories can’t explain why biologically similar organisms show dramatically different lifespans. Most organisms maintain themselves efficiently until adulthood and then, after they can’t reproduce anymore, succumb to age-related damage. Some die swiftly, like flies, and others like we humans can live far beyond reproduction.

Peter Medawar introduced the idea that ageing was a matter of communication failure between generations. Older organisms have no way to pass on genes that helped them survive, if they’ve stopped having offspring. Nature is a highly competitive place, and almost all animals in nature die before they attain old age. Those who do can’t pass newly arising, long-lived genes, so old age is naturally selected against. Genetically, detrimental mutations, these would not be efficiently weeded out by natural selection. Hence they would “accumulate” and, perhaps, cause all the decline and damage.

It turns out that the genes that cause ageing are not random mutations. Rather, they form tight-knit families that have been around as long as worms and fruit flies. They survive for good reasons.

In 1957 George Williams proposed his own theory, called antagonistic pleiotropy. If a gene has two or more effects, with one beneficial and another detrimental, the bad one exacts a cost later on. If evolution is a race to have the most offspring the fastest, then enhanced early fertility could be selected even if it came with a price tag that included decline and death later on. Because ageing was a side effect of necessary functions, Williams considered any alteration of the ageing process to be impossible. Antagonistic pleiotropy is a prevailing theory today, but Williams was wrong: we can offset such effects.

Wear and tear can be countered. Wounds heal, dead cells get replaced, claws regrow. Some species are better at maintenance and repair. Medawar did not agree with Williams that there were fundamental limitations on lifespan. He pointed out organisms like sea turtles live great spans, over a century, showing that aging is not a fundamental limitation. It arises from failure to repair, which can be addressed without implying unacceptable side effects. Some species, like us, have better maintenance and repair mechanisms. These can be enhanced.

Some pursued this by deliberately aging animals, like UC Irvine’s Michael Rose. Rose simply didn’t let fruit fly eggs hatch until half each fly generation had died. This eliminated some genes that promoted early reproduction but had bad effects later. Over 700 generations later, his fruit flies live over four times longer than the control flies. These Methuselahs are more robust than ordinary flies and reproduce more, not less, as some biologists predicted.

Delaying reproduction gradually extends the average lifetime. One side realization: University graduates mate and have children later in life than others. They are then slowly selecting for longevity in those better educated. Education roughly correlates with intelligence. Eventually, longevity will correlate more and more with intelligence.

I bought these Methuselah flies in 2006 and formed a company, Genescient, to explore their genetics. We discovered hundreds of longevity genes shared by both flies and humans. Up-regulating the functioning of those repair genes has led to positive effects in human trials.

So though aging is inevitable and emerges from antagonistic pleiotropy, it can be attacked. Recent developments point toward possibly major progress.

For example, a decade ago, the Japanese biologist Shinya Yamanaka found four crucial genes that reset the clock of the fertilized egg. However old parents are, their progeny are free of all marks of age; babies begin anew. This is a crucial feature of all creatures. By using his four genes, Yamanaka changed adult tissue cells into cells much like embryonic stem cells. Applying this reprogramming to adult tissue is tricky, but it beckons as a method of rejuvenating our own bodies.

So though evolution discards us as messengers to our descendants, once we stop reproducing, not all is lost. In the game of life, intelligence bats last.