Gainesville, Fla. — Researchers around the globe are showing that restricting calories can extend life and slows a range of age-related disorders in mice, rats and other organisms. However, scientists are still unclear about how caloric restriction exerts its age-battling influence.
To help narrow the suspects, researchers at the University of Florida and colleagues at the University of Wisconsin have used age-related hearing loss as an indicator for what may be responsible for slowing down the aging process.
The suspect: Sirt3, a key protein. The researchers found that when Sirt3 is removed from normal mice subjects, caloric restriction loses its anti-aging powers.
More specifially, in normal mice, lowering their calorie intake to 75 percent of a regular diet reduced hearing loss, but in Sirt3-deficient mice, these dietary restriction had no effect. Further, after caloric restriction, mice lacking Sirt3 lost more cellular structures vital for hearing — sensory hair and nerve cells in the ear — than did normal mice on a similarly restricted diet.
A lead author of the study, Christiaan Leeuwenburgh, chief of the biology of aging division in the UF College of Medicine department of aging and geriatric research and a member of the UF Institute on Aging, explained that eliminating Sirt3 seems to be very negative for mitochondrial cell function and allows the accumulation of oxidative stress and damage to neurons and other cells,
“That’s an important clue about the role that Sirt3 plays in protecting cells from age-related damage,” he said in the press announcement.
Age-related hearing loss is the most common sensory disorder among the elderly. The disorder is marked by the death of sensory hair and nerve cells in the inner ear. While those cells are long-lived, they do not regenerate, so their demise means permanent loss of hearing.
But all is not lost, since the environment in which those cells reside can be remodeled over time as damaged organelles such as mitochondria get replaced. Caloric restriction helps to rescue those damaged cells by reducing oxidative damage.
Closer examination also revealed that Sirt3 regulates a mitochondria-based defense mechanism called the glutathione antioxidant system, via which caloric restriction works to help maintain the appropriate chemical balance needed to keep sopping up damaging oxygen-containing chemicals as they appear.
Even more promising for anti-aging researchers, the effects seen in the ear were also observed in brain and liver tissue, suggesting that Sirt3 might have a role well beyond age-related hearing loss, and a potential benefit in cardiovascular and neurological diseases.
The new findings identify Sirt3 as a target around which to focus anti-aging therapeutic efforts, including investigating ways to activate its production in the body.
The findings are reported in the November issue of the journal Cell.
SOURCE: The University of Florida
