DNA Methylation Rate May Determine Lifespan in Mammals
Species within the class Mammalia have a wide range of lifespans, from mice with a lifespan of 2 years to humans with a lifespan of over 100 years. Several non-molecular theories have been proposed to explain these lifespan variations, including body mass and metabolic rate . Alternatively, research on ageing-associated differentially methylated positions (aDMPs) shows age-associated methylation dynamics in humans , , mice  and whales . By looking at several mammals with a broad range of maximum lifespans (Tmax) Lowe et al wanted to determine if age-related methylation changes in aDMPs can predict lifespan and biological age.
The study analyzed aDMPs from mice (Tmax = 4 years), dogs (Tmax = 24 years), naked mole rats (Tmax = 31 years), rhesus macaques (Tmax = 40 years), humpback whales (Tmax = 95 years) and humans (Tmax = 122 years), on a weekly basis, to extend knowledge of the link between Tmax and rate of aDMP methylation. First, Lowe et al looked at the two extremes, mice and humans. Overall, in mice aDMPs had a significantly higher change in methylation than in humans. When looking at all of the mammalian species, aDMPs had a decreased change in methylation the greater the Tmax of the species. Independent of body mass, the change in methylation of aDMPs in humpback whales was higher compared to human aDMPs.
To research if the negative correlation between change in methylation of aDMPs and Tmax holds true within a species, aDMPs from two breeds of dogs, miniature long-haired dachshunds (Tmax = 12-15 years) and flat-coated retrievers (Tmax = 8-10 years) were analyzed. All six conserved aDMPs from the flat-coated retriever showed a significantly increased rate of change in methylation compared to aDMPs from the miniature long-haired dachshund. Finally, the authors determined that the cellular environment causes age-related aDMP methylation changes by using a transchromosomic mouse containing a human chromosome 21 (Tc1 mice). Using 15 human aDMPs to analyze only the human chromosome 21 DNA in these mice, methylation of the aDMPs changed 21 times faster than the same aDMPs in human cells.
This study aimed to find a molecular analysis to determine the lifespan of mammals. Analysis of aDMPs in humans, mice, naked mole rats, dogs, rhesus macaques and humpback whales, found a negative correlation between changes in aDMP methylation and Tmax of the species. This lifespan-associated difference in change of aDMP methylation holds true for dog breeds with different lifespans. Lowe et al also showed that body mass does not always determine lifespan due to humpback whales having a lower Tmax and faster aDMP methylation changes than humans. Further research is needed to determine what the exact role of methylation changes in aDMPs is with respect to mammalian aging.
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