This Shark Lives 400 Years. Its DNA May Explain Why (NY Times)

But looks aside, the species has a surprising capacity: It can live for as long as about 400 years. Now, an international team of scientists from Europe and the United States has mapped the genome of the Greenland shark, offering scientists an opportunity to glean the secret to the shark’s outstanding longevity.

“Any research into the mechanisms of how this animal is able to live for such a long time will at some point need the genome sequence,” said Steve Hoffmann, a computational biologist at the Leibniz Institute on Aging and the Friedrich Schiller University Jena, in Germany, who led the research.

The findings, published as a preprint in bioRxiv, provide a comprehensive assembly of the shark’s genetic makeup. It also provides initial insights into the specific genes and biological mechanisms, including a network of duplicated genes involved in DNA repair, that may be responsible for the shark’s exceptional life span.

A key finding identified a network of 81 genes that were found only in Greenland sharks and that played a role in DNA repair.

The researchers hypothesized that regular DNA repair genes had evolved to exploit the machinery of jumping genes in order to copy and paste more of themselves. That process may have helped them to both counteract the accumulated damage caused by jumping genes and improve the shark’s DNA repair abilities.

At the center of this network was a well-known gene, called TP53, that has been implicated in DNA repair and tumor suppression*.* A study published in 2016 showed that elephants carried 20 copies of this gene, and scientists believe that the gene may account for the animal’s strong resistance to cancer.

https://www.nytimes.com/2024/09/22/science/greenland-sharks-genetics.html

The Greenland shark (Somniosus microcephalus ) is the longest-lived vertebrate known, with an estimated lifespan of ∼ 400 years. Here, we present a chromosome-level assembly of the 6.45 Gb Greenland shark, rendering it one of the largest non-tetrapod genomes sequenced so far. Expansion of the genome is mostly accounted for by a substantial expansion of transposable elements. Using public shark genomes as a comparison, we found that genes specifically duplicated in the Greenland shark form a functionally connected network enriched for DNA repair function. Furthermore, we identified a unique insertion in the conserved C-terminal region of the key tumor suppressor p53. We also provide a public browser to explore its genome.

https://www.biorxiv.org/content/10.1101/2024.09.09.611499v1

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Genes that code for proteins in DNA repair, such as the p53 gene or the Greenland shark gene, need to be modified, such as adding or removing some DNA bases, which can be done very easily with the crispr cas9 gene cutting and adding technique.

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I’ve seen a few good options for DNA repair mentioned here before.

The last one appears to have the most immediate potential.

https://www.researchgate.net/publication/361298407_Disrupting_the_DREAM_complex_enables_proliferation_of_adult_human_pancreatic_beta_cells

All of which are toxic (!!) (except maybe EGCG).

Edit: There’s human testing already with DYRK1A inhibitors mentioned here: DYRK1A inhibitors