Greenland Shark's DNA Holds Clues to Longevity; Senolytics Show Promise in Combating Aging

The Greenland shark (*Somniosus microcephalus*) is the longest-living vertebrate on Earth, with a lifespan that can reach 400 years or more. A recent study shared via biorxiv suggests the key to their longevity lies in their extraordinary ability to repair their DNA. Scientists have sequenced the Greenland shark's DNA, revealing a genome with over 6.5 billion base pairs, more than twice that of humans. The shark possesses unique DNA repair genes, similar to those found in long-lived animals like Galapagos giant tortoises and the Greenland whale. The protein TP53, the "guardian of the genome", plays a crucial role in protecting cells against mutations and degenerative diseases. In other news, research on childhood cancer survivors reveals insights into accelerated aging. Greg Armstrong, principal investigator of the Childhood Cancer Survivorship Study at St. Jude, notes that while modern treatments are increasingly effective, their long-term side effects can be devastating. "Of these children, 85% will beat their cancer, but the victory comes at a price. We know they will have a shorter lifespan. Many of them die prematurely from chronic diseases such as cardiovascular conditions, strokes, or secondary cancers, which appear much earlier than normal. We discovered about a decade ago that this phenomenon occurs because they age rapidly, beyond their biological age," Armstrong stated to The Guardian. Kirsten Ness, a physical therapist and clinical epidemiologist at St. Jude, found that the cardiac function, flexibility, respiratory capacity, and mobility of survivors aged 24 to 41 were similar to those of much older individuals. Cellular senescence, where cells lose the ability to divide but remain active in a dysfunctional state, is a key factor in aging. In childhood cancer survivors, aggressive treatments at a young age promote a premature accumulation of senescent cells, accelerating the degradation of physiological functions and increasing the risk of age-related conditions. Senolytics, drugs that eliminate senescent cells, are gaining attention. Greg Armstrong is leading a clinical study involving survivors with signs of frailty and senescence markers, testing the impact of Dasatinib and Quercetin, or Fisetin on physical function. Long-term monitoring will assess whether these drugs can extend life expectancy. Johannes Grillari, director of the Ludwig Boltzmann Institute for Traumatology in Vienna, presented the potential of senolytics at the British Society for Research on Ageing conference in September 2024. He highlighted that senescent cells are a common factor in age-related diseases, and their elimination could reduce inflammation and improve tissue regeneration. Researchers are also exploring senolytics for rejuvenating organs from older donors to improve transplant success rates. A study showed that organs with more senescent cells have a higher risk of transplant failure. Clinical trials are underway to assess whether Dasatinib and Quercetin can slow the progression of early-stage Alzheimer's disease and improve physical function in patients with chronic lung conditions. Professor Tohru Minamino from Juntendo University in Japan suggests a "vaccination against aging" as a safer approach, targeting only inflammatory senescent cells. His team developed a vaccine based on the GPNMB protein, showing promising results in mice. They are now working on an mRNA-based vaccine to train the immune system to selectively eliminate inflammatory senescent cells, potentially treating conditions like Alzheimer's, chronic lung diseases, and age-related frailty. Researchers emphasize that eliminating senescent cells alone is not enough to combat aging. Dr. Stijn Meijnikman notes that the body must still have the capacity for regeneration. He also noted, "In the future, we will be able to treat more and more elderly patients, but for now, we must accumulate more evidence regarding the effectiveness of senolytics in humans."