Decoding Lifespan: New DNA Research Unveils Secrets of Aging

Researchers at UCLA have identified a significant relationship between patterns of DNA methylation and the lifespan of mammals. Through detailed examination, they discovered that DNA methylation, a form of epigenetic modification, plays a crucial part in aging, affecting different species and being closely related to both evolutionary and developmental mechanisms.

Leading innovative studies on mammalian aging and lifespan, UCLA scientists collaborated with a global team from the UCLA David Geffen School of Medicine and UCLA Health. They have published two papers illustrating DNA changes that are consistent across humans and other mammals throughout history, and are linked with lifespan and various other characteristics.

According to the senior author of both studies, Steve Horvath, Ph.D., ScD, they found that mammalian lifespans are tightly connected to specific DNA chemical modifications, known as methylation or epigenetics. Longer-lived mammals show more distinct DNA methylation patterns, while those of shorter-lived species exhibit less pronounced, more level methylation layouts.

Professor Jason Ernst of UCLA stated that their innovative technology, designed to measure DNA methylation levels across mammals, combined with the collaboration of many researchers, generated a distinctive data set. This, when evaluated with sophisticated computational and statistical tools, provided a profound comprehension of the association between DNA methylation, lifespan, aging, and other biological processes among mammals.

The two studies, published in Science and Nature Aging, focused on DNA methylation, specifically cytosine methylation, a chemical alteration of one of the four building blocks of DNA. This modification allows cells to regulate gene expression – turning genes on or off – and the studies examined differences in DNA methylation across species at areas where DNA sequences are generally identical.

A team of almost 200 researchers, known as the Mammalian Methylation Consortium, collected and analyzed methylation data from over 15,000 animal tissue samples representing 348 mammalian species. They observed that alterations in methylation profiles correspond closely to genetic changes through evolution, showing a combined evolution of the genome and epigenome that affects the biological attributes of different mammalian species.

Among the findings:

• Methylation, demonstrated by the epigenetic “marks” it creates, has a notable correlation with maximum lifespan across mammalian species.
• Maximum lifespan in a species is related to specific developmental processes, influenced by particular genes and transcription factors.
• Molecules whose methylation levels correlate with maximum lifespan differ from those that alter with chronological age, indicating distinct molecular pathways.
• Evolution influences not only genetic levels but also epigenetic ones. The authors’ public database illustrates that DNA methylation is subject to evolutionary forces.
• The researchers used a portion of the database to study 185 mammal species, identifying age-related methylation level changes. They created a “universal pan-mammalian clock,” a mathematical formula that accurately estimates age across species, as published in Nature Aging.
• UCLA’s Horvath previously introduced an epigenetic clock for age measurement in humans in 2011. The recent work expands on this, showing that a single formula can gauge age across mammalian tissues and species.

Further findings in the Nature Aging study include:

• The pan-mammalian clocks are highly accurate across species with varying lifespans, from mice to whales.
• The universal clocks could be valuable for preclinical studies as predictors of mortality risk in humans and mice.
• The study identified specific areas in the genetic material that either gain or lose methylation with chronological age.
• The research connected developmental pathways with chronological aging effects and tissue deterioration, challenging the belief that aging is driven solely by random cellular damage.
• The discovery of the pan-mammalian clocks offers strong evidence that aging processes are consistently preserved through evolution and closely linked with developmental processes across all mammalian species.

References for these studies were published on 11 August 2023, in Science and Nature Aging.

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