The Evolution of Aging

Scientists have long known that genes play an important role in lifespan and longevity, and they have made significant progress in understanding the complex genetic mechanisms of aging. Evolutionary geneticists are now building on these discoveries to see if there is an adaptive component to life span.

“Since lifespan can be inherited, this means it can evolve over time in populations,” says biology doctoral student Annalise Paaby. “If that’s the case, then we should not only be able to identify some of the genes that determine how long an organism lives, but also be able to understand how natural selection acts on those genes to eventually produce the different lifespans that animals have.”

Working in the lab of Associate Professor of Biology Paul Schmidt, Paaby has been studying the microevolutionary forces affecting lifespan in Drosophila melanogaster—the common fruit fly. “If we have the hypothesis that different environments exert different selection pressures, and these pressures favor different genes, then this could explain why you get different lifespans,” Paaby says. “One of the many reasons fruit flies are such a good model for evolutionary genetics is because they have natural populations that exist across a wide geographic area that has lots of environmental variation.”

"If you want to make the claim that you found something adaptive, you have to come at it from many levels." - Annalise Paaby

All the genes currently identified as affecting longevity also affect multiple other traits. So, although scientists don’t believe there would ever be a case where natural selection would favor an allele—or version—of a gene that would cause a short lifespan, that allele might be favored because it confers other traits that benefit the fitness of the species. One tradeoff well demonstrated across animal models is that alleles which result in a short life span also result in high reproductive success, and vice versa.

Paaby’s research tests the hypothesis that fruit flies living in high latitudes must have adapted to survive seasonal cold stress, requiring alleles that confer a longer lifespan and the ability to resist stress, but also lower fecundity. In flies occupying lower latitudes, she posits, these alleles would be selected against because they confer only a disadvantage, since the tradeoff between reproductive success and stress tolerance is no longer beneficial. Her work builds on mutational genetics research, which induces lab derived mutations at specific genes in an organism to determine how they impact phenotype—the observable characteristics or traits of an organism. Paaby sequenced the insulin receptor gene—previously identified by mutational screens as affecting aging in Drosophila—in natural populations of fruit flies collected in orchards from Maine to Florida. 

She found a polymorphism, a naturally occurring mutation, in the insulin receptor gene that varies across latitude. “One polymorphism allele was more common in northern fly populations and increased with latitude,” Paaby says, “and another was more common in southern populations and decreased with latitude.” When she tested this polymorphism for functional significance in the lab, she discovered that the allele more common in high latitudes conferred stress tolerance and the allele more common in low latitudes conferred high fecundity. 

Paaby has also been in contact with researchers in Australia who, following her research, sequenced the same gene in fruit fly populations in their country. They too found a matching polymorphism showing the same latitudinal pattern. “This is exciting,” Paaby explains, “because we know these populations have been separate for a really long time and were founded by different source populations. The fact that this pattern is repeating itself suggests it is not random and that there is a deterministic process causing it.” Her next step is to test the alleles to see if they impact lifespan. “I have every expectation,” she says, “that the high-latitude allele that confers the stress tolerance phenotype is also going to confer the longer lifespan phenotype.”

Additionally, Paaby has tested the methuselah gene—also known to affect fruit-fly lifespan—for functional significance. Schmidt published a paper in 2000 identifying a polymorphism in methuselah that showed a pattern of variation from north to south, and Paaby found that this polymorphism also resulted in differences in lifespan, fecundity and stress tolerance.

Paaby believes her research provides a powerful example of how researchers can apply findings from mutational genetics to natural genetic variation in order to more profoundly understand the nuances of genetic function. “If you want to make the claim that you found something adaptive, you have to come at it from many levels,” she says. “You have to explain its genetics, its phenotype, and you have to make a case that you can correlate the environment to the genes and the phenotype. My research helps complete that circle.”