Scientists Discover Nature’s Secret to Healthy Longevity

Researchers at Bar-Ilan University reveal protein changes linked to longevity throughout mammalian evolution.

Over the past several decades, human lifespan has steadily increased. However, this progress has also led to a growing proportion of the population suffering from age-related diseases such as cancer, neurodegenerative disorders, and diabetes. Extending both lifespan and healthspan, the period of life spent in good health, requires a deeper understanding of the biological mechanisms that promote healthy aging.

In the natural world, mammalian lifespans vary enormously, ranging from just 1 to 2 years in some rodents to more than a century in species like whales and humans, a striking 100-fold difference. Such remarkable diversity raises an important question: what biological factors allow long-lived mammals to maintain health well into old age?

A new study published in Nature Communications by researchers at Bar-Ilan University addresses this question by drawing on evolution itself, the longest and most extensive natural experiment, to uncover the secrets of longevity.

The research was led by Prof. Haim Cohen, Director of the Sagol Healthy Human Longevity Center at Bar-Ilan University’s Goodman Faculty of Life Sciences in collaboration with Dr. Sagi Snir of the University of Haifa.

Tracing Protein Changes Across Species

Sarit Feldman-Trabelsi, a PhD student in Prof. Cohen’s lab, developed a novel computational tool called PHARAOH (Positive posttranslational Modifications Regulator of Healthspan). Using advanced statistical methods, PHARAOH compared protein sequences across 107 mammalian species with varying lifespans. This approach enabled the researchers to trace specific protein changes, particularly posttranslational modifications (PTMs) such as acetylation, throughout evolution and identify those consistently enriched in long-lived species.

PTMs regulate essential cellular processes and have been linked to increased resilience against age-related diseases, including cancer. By comparing long-lived and short-lived mammals, the team uncovered consistent protein modifications associated with extended lifespan. Experimental validation confirmed that the PTMs identified by PHARAOH play significant biological roles in aging and disease resistance.

Implications for Healthspan and Disease Resistance

“Our findings offer a promising path toward understanding how protein modifications can protect against age-related diseases and promote longer, healthier lives,” said Prof. Cohen. “By pinpointing the PTMs linked to longevity, we can begin exploring therapeutic strategies that mimic these natural, evolutionarily conserved mechanisms.”

One striking insight from the study is how large mammals such as whales exhibit dramatically lower cancer rates despite having significantly more cells than smaller animals. The research revealed that certain PTMs found in these species likely serve protective roles against cancer, shedding light on molecular strategies for disease resistance and longevity.

These findings pave the way for future research into therapies that target proteins and modifications associated with healthy aging. By leveraging nature’s own longevity strategies, the researchers aim to uncover new methods to slow aging and combat diseases such as cancer, Alzheimer’s, and diabetes.

Reference: “The mammalian longevity associated acetylome” by S. Feldman-Trabelsi, N. Touitou, R. Nagar, Z. Schwartz, A. Michelson, S. Shaki, M. Y. Avivi, B. Lerrer, S. Snir and H. Y. Cohen, 22 April 2025, Nature Communications.
DOI: 10.1038/s41467-025-58762-x

This study was funded by the SAGOL Network.