New Delhi: A rare ‘orderliness’ in genes might be the secret to a long life, according to a new paper in the journal Science Advances, published on 7 October. A group of international scientists studied 194-year-old tortoise Jonathan, the oldest living terrestrial mammal, to understand the reason behind his long life.
The scientists looked at two elements – Jonathan’s genome, consisting of his DNA sequence and genetic instructions, and his DNA methylome, which consists of small chemical tags influencing how genes are switched on or off in the body.
Through this, they found that Jonathan had uniquely low methylation entropy in certain parts of his system. Methylation entropy is the phenomenon of disorderliness or variability in genes, which usually happens as one ages. However, Jonathan showed very low entropy, especially in the regions controlling mitochondrial energy production, making it seem like he had not aged at all.
According to the study, this shows a pathway through which researchers can now approach longevity – by protecting mitochondrial decline and energy production in the genes.
“It might be possible to protect mitochondria from the ageing-related consequences of disordered gene expression, thereby extending a healthy human lifespan,” said Stephen Clark, scientist at Vanderbilt-Ingram Cancer Centre and senior corresponding author of the study, in a press release.
Clark also runs the Kallel Foundation, a non-profit organisation focused on longevity research. He said in the press release that his foundation will soon work on clinical trials based on this study and other ageing-related animal studies to develop longevity drugs.
Why Jonathan?
The 194-year-old Aldabra tortoise Jonathan lives on Saint Helena Island, a British Overseas Territory, and is a subspecies of the Seychelles tortoise. When Clark heard about Jonathan and his long life since 1832, he wanted to study the tortoise using blood samples. While the request was rejected, he was allowed to scrape some tissue from inside his cheek, providing Clark access to Jonathan’s DNA for sequencing.
It was this tissue that resulted in the massive, collaborative study to understand how a mammal could live this long.
Jonathan’s genome was compared with other Aldabra tortoises and other species too, to understand which aspects of his genes were ageing and how. The scientists found that he had many unique genetic variants, including those involved in DNA repair, controlling damage to cells, metabolism and mitochondrial function.
It was the last one which interested scientists the most, because they found that Jonathan’s genes had actively avoided entropy, or ‘randomness’, which is a factor that most genes experience with age.
The scientists compared Jonathan’s methylome with four other Aldabra tortoises ranging from five years old to older adults and found substantial differences in methylation and methylation entropy, indicating that it is not a factor in every Aldabra tortoise.
(Edited by Aakriti Handa)