Building on two decades of research, scientists at University of Texas Southwestern have found that enhancing autophagy, a process of natural "cellular housekeeping" within our bodies, can extend the lifespan of mice by 10 percent and reduce age-related illnesses. The study could serve as an important step toward treating degenerative diseases like Alzheimer's in humans.
Autophagy (from the Greek words for "self" and "eating") is a highly-desirable physiological process that destroys aged or damaged cellular components and recycles them to build new, healthier cells. Scientists believe that one of the reasons why exercise and calorie-restricted diets tend to improve our health and lengthen our lives is that they subject cells to heightened levels of stress, which in turn boosts autophagy in the body.
Unfortunately, our ability to perform this valuable "cellular spring-cleaning" declines with age. But what if that decline could be stopped?
In a recent study, a team led by doctors Salwa Sebti and Álvaro Fernández at UT Southwestern set out to find whether artificially and permanently increasing the level of autophagy in mice would affect their longevity and overall health.The researchers achieved this through genetic engineering, by mutating the protein Beclin-1 (which helps regulate autophagy and cell death) so it would bind less tightly to its inhibitor Bcl-2.
As a result of this tweak, the genetically-engineered mice showed consistently higher levels of autophagy in all their organs and throughout their lives. Previous studies had suggested these mice were partially immune to the mouse equivalent of Alzheimer's disease, but the latest work goes into significantly more depth, suggesting they also live about 10 percent longer lives and are generally healthier, since they are less likely to develop age-related cancers and pathological changes in the heart and kidneys.
"These studies have important implications for human health and for the development of drugs to improve it," said Dr. Beth Levine, director of the Center for Autopathy Research at UT Southwestern. "They show that strategies to increase the cellular housekeeping pathway of autophagy may retard aging and aging-related diseases."
The results suggest that it should be safe to permanently increase autophagy to treat neurodegeneration and other diseases by developing drugs that specifically target the binding between Beclin-1 and Blc-2.
Levine and her team are now working with other researchers to synthesize such a drug, with the intent to target human patients.
The study appears in the latest edition of the journal Nature.
Source: UT Southwestern
