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Longevity Briefs: Is This The Limiting Factor For Human Lifespan?

Posted on 23 May 2023

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: The activity of our genes can be controlled by the addition or removal of molecular ‘tags’ called methyl groups. These tags are added to specific sites on the DNA molecule and generally suppress the genes they are tagging. Throughout life, these tags are added and removed. This can cause deleterious changes in gene expression, such as by ‘turning off’ important genes. Scientists think that these changes could play an important role in the ageing process – something which is backed up by evidence that species with higher rates of methylation tend to have shorter maximum lifespans.

What did the researchers do: In this preprint study, researchers used data from other studies to investigate the relationship between DNA methylation and maximum lifespan in seven species of mammal, with the shortest-lived being mice and the longest-lived being humans. Specifically, they studied the rates at which DNA was methylated in cells from the skin and from the blood. Unlike previous studies, they looked specifically at sites within the DNA at which methylation is known to correlate with the ageing process, and that were common to all species studied.

Key takeaway(s) from this research: The researchers found that there was a consistent mathematical relationship between methylation rates and maximum lifespan, where higher rates of methylation in a species were inversely proportional to maximum lifespan. This relationship was stronger for blood cells than for skin cells. This may have been because much of the skin cell data came from bats, whose maximum lifespan is less well studied than other species.

Proportion of conserved sites methylated in blood cells from seven species throughout life.
DNA methylation rates scale with maximum lifespan across mammals

The fact that this relationship seems to follow a strict scaling law could suggest a few things. One possibility is that methylation is a fundamental limiting factor for a species’ maximum lifespan, and so the longer-lived species are those that have evolved mechanisms for slowing it down. Another possibility is that some underlying mechanism that restricts maximum lifespan also promotes methylation, and that methylation itself is not the limiting factor. 

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    DNA methylation rates scale with maximum lifespan across mammals

    Title image by Sangharsh Lohakare, Upslash

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