One Foot on the Gas, One on the Brake
New BIU research reveals how one protein precisely balances a powerful longevity molecule, opening new paths toward healthier aging
Researchers at Bar-Ilan University have uncovered a key biological mechanism that helps the body stay healthier for longer. The study, recently published in Proceedings of the National Academy of Sciences (PNAS), explains how the protein, Sirt6, carefully regulates a critical longevity molecule, protecting against age-related decline and disease.
The findings shed new light on how the body maintains balance as it ages, and may pave the way for future therapies designed to extend not just lifespan, but health-span.
A master regulator of healthy aging
Sirt6 has long intrigued scientists studying aging. Often described as a master regulator of longevity, the protein has been shown to protect against a wide range of age-related conditions, including cancer, diabetes, chronic inflammation, and physical frailty. Its effects closely resemble those of calorie restriction—a dietary intervention known to extend lifespan and strengthen the body’s natural repair systems in many animal models.
But until now, researchers did not fully understand how Sirt6 produces these powerful protective effects.
The surprising role of a tiny gas molecule
One of the best-known benefits of calorie restriction is its ability to boost production of hydrogen sulfide (H₂S), a small gas molecule with outsized importance. In the right amounts, H₂S supports wound healing, cardiovascular health, brain function, and cellular resilience.
The new study shows that hydrogen sulfide levels naturally decline with age, weakening these protective systems. This drop may be one of the reasons aging tissues become more vulnerable to disease and damage over time.
Precision, not excess
The Bar-Ilan research team discovered that Sirt6 mimics the benefits of calorie restriction, but with remarkable precision. Rather than simply increasing hydrogen sulfide levels across the board, Sirt6 fine-tunes its production, boosting it when beneficial while preventing dangerous overproduction.
“This protein acts like the body’s internal version of calorie restriction,” explains Prof. Haim Cohen, who led the study. “Sirt6 has one foot on the gas and the other on the brake: promoting hydrogen sulfide production when it supports health, but keeping it under tight control so it doesn’t become harmful.”
This balance turns out to be critical. While hydrogen sulfide is protective at low levels, excessive amounts can be toxic. The study shows that healthy aging depends less on maximizing longevity molecules and more on maintaining their optimal range.
A new way to think about longevity
The findings challenge a common assumption in aging research, that more of a “good” molecule is always better. Instead, the study highlights metabolic balance as a cornerstone of long-term health.
“Our findings reveal one of the body’s natural strategies for preserving health during aging,” says Prof. Cohen. “By understanding how Sirt6 maintains precise control over hydrogen sulfide, we gain new insight into the molecular logic of healthy aging—and identify promising targets for interventions that slow age-related decline.”
Building on a growing body of longevity research
The study builds on years of work by Prof. Cohen and his team showing that Sirt6 extends lifespan in mammals and protects against multiple age-related diseases. This latest research takes the story a step further, revealing how Sirt6 achieves these effects at the molecular level.
The research was conducted at the Sagol Healthy Human Longevity Center at Bar-Ilan University and led by Prof. Cohen together with PhD student Noga Touitou. It was carried out in collaboration with the laboratory of Prof. Rafael de Cabo at the National Institute on Aging in Baltimore, Maryland.
The study was supported by grants from the Sagol Healthy Human Longevity Center, the Binational Science Foundation, the Israel Science Foundation, and the Ministry of Innovation, Science and Technology.
Together, these findings position Bar-Ilan University at the forefront of global longevity research, advancing our understanding of how the body protects itself over time, and how science might one day help more people age with health, strength, and resilience.