While human lifespans have dramatically increased in recent decades, this progress has been accompanied by a surge in age-related diseases. As scientists seek to extend not just lifespan but also healthspan, a deeper understanding of the biological mechanisms behind aging is crucial, scientists at Bar-Ilan University said. While lifespan refers to how long a person lives, healthspan refers to how long a person lives in good health.

The new research sheds light on how long-lived mammals, such as whales, manage to avoid common age-related diseases despite their large size and the substantial number of cells in their bodies. Findings published in the peer-reviewed Nature Communications journal suggest potential therapies that may prevent diseases like cancer, Alzheimer’s, and diabetes, all of which are on the rise as the human population ages.

The study, led by Prof. Haim Cohen of Bar-Ilan University’s Sagol Healthy Human Longevity Center, in collaboration with Dr. Sagi Snir of the University of Haifa, used a novel computational tool called PHARAOH (Positive posttranslational Modifications Regulator of Healthspan). Developed by PhD student Sarit Feldman-Trabelsi, PHARAOH compares protein sequences across 107 mammalian species with varying lifespans, pinpointing post-translational modifications (PTMs)—chemical changes to proteins—that are enriched in long-lived species.

“Our findings offer a promising path toward understanding how protein modifications can protect against age-related diseases and promote longer, healthier lives,” said Cohen.

Through this approach, the researchers identified specific PTMs linked to enhanced resilience against aging and disease. They also confirmed experimentally that these modifications play critical roles in cellular protection. The potential applications of these discoveries are profound, particularly in developing new therapies and preventive measures for age-related conditions.

“By pinpointing the PTMs linked to longevity, we can begin exploring therapeutic strategies that mimic these natural, evolutionarily conserved mechanisms,” Cohen said.

One of the most promising outcomes of the study is the possibility of developing treatments that mimic or enhance the identified PTMs. These therapies could help protect against age-related diseases like cancer, Alzheimer’s, and diabetes, by targeting the proteins involved in cellular resilience. In particular, the research suggests that certain PTMs found in large mammals like whales may offer a natural defense against cancer, despite their larger number of cells. This insight could lead to the development of new cancer prevention strategies inspired by the protective mechanisms of these animals.

Furthermore, the findings raise the possibility of using gene editing technologies, such as CRISPR, to introduce beneficial PTMs into human cells. This could provide a novel approach to slowing down the aging process or preventing age-related diseases altogether. The study also hints at the potential for personalized medicine, where doctors could tailor treatments based on an individual’s PTM profile.

The identified PTMs could also serve as biomarkers for aging, allowing doctors to assess a person’s risk for age-related diseases with blood tests. This could lead to earlier intervention and more effective prevention strategies.

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