Natural Longevity: Genetic Insights from Long-Lived Animals
Comparing the genomes of especially long-lived animals reveals genes potentially involved in longevity
We, modern sinners, are nowhere close. But we’re not giving up on longer healthy lives yet.
No immortality-promising stone is left unturned: drugs (such as metformin or rapamycin), supplements (such as resveratrol), blood exchange and/or dilution, custom-made molecules, stem cells,…. Or why not try some fasting or calorie restriction (which may not work as well as you think)? Or have some red wine.
For all the above, the extent of the intervention’s proclaimed influence — if any — varies among individuals. Your body will respond differently to certain changes than someone else’s.
Right now, though, these options are very much like searching for needles in a haystack. In the dark.
We need a magnet, and for that, we need to understand the many intertwined processes that underlie aging.
We can also study healthy centenarians and try to identify shared traits, such as gene variants, lifestyle factors, or physiological traits (for example, their methionine metabolism). Correlation is not causation, of course, but it may give us a starting point.
Why stick to humans, though? If we look at animals, on average, body size tends to correlate with lifespan across species. (Interestingly, within species this seems to be the reverse, smaller is better.)
However, if we look at different species, we begin to see anomalies. And anomalies can teach us a lot. Some relatively small animals live (a lot) longer than their body size suggests. The naked mole-rat slows down aging through hibernation and bats use autophagy to cheat father time. Some fish even get better with age.
What if we extend the study of centenarians to include other mammals?
A new study analyzes the genomes of particularly long-lived mammals to see if there are certain shared ‘longevity’ genes. After all, if we find the same genes (or gene versions) to correlate with longevity across a variety of species, there’s a good chance they’re involved in something fundamental — they are ‘conserved’ in evolutionary biology parlance.
To start, the researchers trawled through lifespan and body mass data on 987 species of mammal. Based on that data, they identified 11 species with a longevity quotient >1.6. This is the ratio of observed versus predicted lifespan. Above 1 means the species lives longer than its body mass seems to suggest.
Here are the 11 species: human, Sumatran orangutan, pigtailed macaque, common marmoset, grey mouse lemur, naked mole-rat, bowhead whale, killer whale, Brandt’s bat, little brown bat, and Hoffman’s two-toed sloth.
As a control group, they selected 25 other species of mammal.
Then, the scientists went looking for genetic differences between the long-lived and regular-lifespan mammals, based on information from GenAge, a curated database of genes implicated in the aging process, to zoom in on potentially interesting genes.
They found 16 positively selected genes and 23 rapidly evolving genes in the long-lived species. The majority of those genes is known to be involved in (among others) one of three things:
- Immune response-related pathways
- The insulin/IGF-1 pathway
- Cancer progression
That last case, cancer progression-related genes, included 7 genes with convergent amino acid changes, suggesting that long-lived species have evolved similar ways to cope with cancer, which extends their lifespan.
Together, these findings provide insights into how evolution reversibly adjusts lifespan and represents candidate genes and pathways for further experimental exploration.
Evolution is cleverer than we are.