The age of almost any mammal can now be accurately estimated from a tissue sample by analysing chemical tags added to DNA. The finding comes from a study of nearly 200 species and could overturn our understanding of ageing.
The team involved says the fact that all mammals seem to have the same 鈥渁geing clocks鈥� shows that ageing is the result of developmental programs that have been retained during the evolution of mammals, rather than being solely due to accumulating damage.
If something is conserved across different species, it is a sign that it is biologically important, says at the University of California, Los Angeles, who led the work. 鈥淵ou simply would not be able to build these pan-mammalian clocks if there wasn鈥檛 something here that鈥檚 conserved,鈥� he says.
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The clocks are already being used by other teams to help study ageing 鈥� and potential anti-ageing therapies. For instance, one team has shown that giving old mice young blood sets these clocks back in many organs, says Horvath.
The new finding is a result of looking at which bits of DNA in cells have chemical tags called methyl groups added to them. These methyl groups get added to or removed to alter the activity of genes, in what are known as epigenetic changes.
These methylation patterns vary greatly in different types of cells. However, in 2011, Horvath showed that in human blood cells, certain small bits of DNA accumulate methyl groups in a consistent way over time, and so can be used .
In 2013, his team identified that signals the age of any human tissue, not just blood, suggesting there is an ageing process common to all human cells. The team has also identified 鈥渆pigenetic clocks鈥� for different species, such as elephants.
The latest clocks are based on studies of nearly 12,000 samples from 59 different tissue types across 185 species of mammal. This included several species each of lemurs, whales, goats, rhinos, bats, seals, kangaroos, wallabies, shrews and sloths, as well as the rock hyrax, Pacific walrus and platypus.
鈥淲hat we show is that there are these certain locations 鈥� genomic regions 鈥� that gain methylation in an extremely consistent way in all of these very different mammalian species,鈥� says Horvath.
Based on these regions, the team has developed three versions of the clock. One estimates an individual animal鈥檚 age in years. Another estimates age relative to the maximum lifespan of the species, which can be converted into years if the maximum lifespan is known. Because the maximum lifespan isn鈥檛 known for some species, the team also developed a third version that calculates age relative to that at which sexual maturity is reached.
The clocks are about 97 per cent accurate overall, but this varies from species to species. For bowhead whales, they did particularly poorly, but this is probably because the existing method used to calculate the age of bowheads is inaccurate, says Horvath.
Because the clocks work in such a wide range of mammals, he thinks they will work for any mammal, not just the species in the study.
The team also did a number of other tests, showing, for instance, that the clocks run more slowly in mouse strains genetically engineered to live longer, and that they get set back to an earlier age when specialised cells are reprogrammed to turn them back into stem cells.
鈥淭his is a really good study,鈥� says David Gems at University College London.
The findings run counter to the overriding thinking on what causes ageing. The dominant idea is that it is due to accumulation of damage, for example to DNA, such as that caused inside cells by highly reactive molecules known as free radicals. But Gems says the epigenetic clocks add to growing evidence for an alternative idea that he calls the programmatic theory.
The basic idea of this is that the body鈥檚 failure to completely switch off the developmental processes that build our bodies is the key to ageing. For instance, pruning connections between neurons in the brain is a key part of development when we are young, but might contribute to cognitive decline in later life.
鈥淚t doesn鈥檛 argue that molecular damage plays no role in ageing, rather that ageing is largely caused by other things,鈥� says Gems.
Horvath found many of the sites that gain methylation with age are next to genes related to development. These results support the idea that ageing is linked to developmental processes common to all mammals 鈥� and probably all vertebrates, too, says Horvath.
鈥淭hat to me is a smoking gun, that there are these processes that are conserved,鈥� he says. 鈥淭here must be some sort of a program.鈥�
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Read more: Why your real age may be older 鈥� or younger 鈥� than your years
