We might have found a new way to extend the lifespan of many mammals, including people.
A study of 15,000 tissue samples from 348 mammal species has shown it is possible to predict their maximum lifespan by looking for the presence or absence of labels known as epigenetic markers at specific sites in the genome. What鈥檚 more, these could be causal. That is, altering the epigenetic markers might increase maximum lifespans.
鈥淚 do think it is quite possible,鈥� says at Altos Labs in Cambridge, UK. Other groups have managed to by making epigenetic changes. 鈥淪o probably you can change the epigenome one way or another in a mouse and then the mouse will live one or two years longer,鈥� says Horvath.
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Many of the differences between species aren鈥檛 due to variations in genes, but differences in how those genes are used 鈥� when they get turned on or off, for instance. One key way that genes are regulated is by adding epigenetic markers to DNA 鈥� chemical labels that change gene activity without altering the underlying sequence.
A common epigenetic change involves the addition of a small molecule called a methyl group to the DNA letter C, in a process known as methylation. Horvath has led a seven-year project that looked at methylation patterns in up to 60 different tissue types in 348 mammal species. The work was funded by private donors, but .
His team has already shown that the methylation patterns in DNA sequences shared by all mammals can be used to estimate the age of individual animals. Now, the team has used supervised machine learning to find methylation patterns linked with the maximum lifespan of species in sequences shared by all mammals.
鈥淚f you find a piece of skin or a tail or whatever from a species you know nothing about and you give me that sample, I can tell you the maximum lifespan of the species, the gestation time of the species and the age at sexual maturity,鈥� says Horvath. 鈥淭o me, that鈥檚 quite remarkable.鈥�
These methylation patterns vary somewhat from tissue to tissue and the predicted maximum lifespans are approximate. The method is least accurate for people, predicting a maximum of around 98 years, whereas Jeanne Calment, thought to be the world鈥檚 longest lived person, made it to 122 years. Calment鈥檚 age has been disputed, but others are verified as living up to 119.
鈥淲e are complete outliers,鈥� says Horvath, with our gorilla cousins living to 60 years at most.
For 17 of the 348 species, including humans, females consistently had longer predicted maximum lifespans.
The team also found that lifestyle factors such as caloric restriction or body weight had little effect on predicted maximum lifespans.
鈥淚 think it鈥檚 amazing work,鈥� says at the University of Birmingham in the UK. 鈥淚t鈥檚 interesting that these methylation sites tend to occur in genes related to development, which fits the idea that development to some degree influences rates of ageing. In other words, perhaps mice age 20 to 30 times faster than human beings because they develop 20 to 30 times faster than human beings.鈥�
鈥淲hether this link between epigenetic signatures and lifespan is causal is the big question,鈥� he says. 鈥淢y intuition is that some of these epigenetic signatures are indeed reflective of causal processes.鈥�
bioRxiv
