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Epigenetic Patterns Predict Vertebrate Species' Lifespans

NEW YORK – Researchers have found a way to gauge how long-lived an animal species is based on the density of methylation at particular genomic sites.

Aging is associated with epigenetic changes, and a person's age can be estimated using an epigenetic clock. A team of Australian researchers sought to examine whether other species' lifespans can similarly be gleaned from epigenetic patterns.

The researchers looked at promoter CpG density among more than 250 vertebrates with known lifespans to build a predictive model. They found that CpG density at 42 promoters could accurately predict lifespan in vertebrates, as presented today in Scientific Reports. This model, they added, could be applied to determine the lifespan of extinct species as well as extant ones whose lifespans are difficult to measure.

"In this study, we have shown that CpG density correlates strongly with lifespan across the five most speciose vertebrate classes," Simon Jarman of the Commonwealth Scientific and Industrial Research Organisation and his colleagues wrote in their paper. "Our results also enabled the construction of a model that can predict lifespan accurately from only a small number of genomics features."

To build their model, the researchers first uncovered 252 vertebrates that not only had a genome in the NCBI database, but also a maximum lifespan in the AnAge database and evolutionary divergence times in the TimeTree database. The lifespans of these animals ranged from 1.1 years for the turquoise killifish Nothobranchius furxeri to 205 years for the rougheye rockfish Sebastes aleutianus.

They based their lifespan predictor on methylation at 42 promoters and noted a high correlation between known and predicted lifespan in their training set. Across all species, they reported a median absolute error of 3.72 years and a maximum relative error of 5.9 percent. Though the model was accurate across different vertebrates, the researchers noted that its accuracy was highest among mammals, which were more common in the training set.

The researchers next applied their predictor to determine the lifespan for two extinct members of the Elephantidae family, the woolly mammoth Mammuthus primigenius and the straight-tusked elephant Palaeoloxodon antiquus. From this, they estimated that both M. primigenius and P. antiquus likely lived to be about 60 years, similar to the reported 65-year lifespan of the African elephant.

They likewise calculated that the passenger pigeon Ectopistes migratorius, which went extinct in 1914, had a likely lifespan of about 28 years. This, they noted, was in line with the estimated age of the last passenger pigeon, Martha, who was thought to be between 17 years and 29 years old at her death.

Meanwhile, the researchers also applied their tool to gauge the lifespan of humans and their closest relatives, including chimpanzees and the extinct Denisovans Homo denisova and Neanderthals H. neanderthalensis. For humans — where estimating a maximum lifespan is controversial, as it has more than doubled with the advent of modern medicine — it estimated a 38-year lifespan, similar to the 39.7-year lifespan estimate for chimpanzees. Denisovans and Neanderthals both had estimated lifespans of 37.8 years.

This tool could be used to determine the lifespans of especially long-lived animals, whose ages are difficult to track as they outlive researchers, the researchers noted. To that end, they estimated bowhead whales to live to 268 years, nearly 60 years longer than the oldest individual to date. 

Such lifespan estimates could be used to guide wildlife management approaches, including sustainable harvesting of fish and other aquatic animals, and to maintain population viability.