Scientists find molecular trigger that helps prevent aging and disease

Scientists find molecular trigger that helps prevent aging and disease

ScienceDaily (Nov. 23, 2009) — Researchers at Mount Sinai School of Medicine set out to address a question that has been challenging scientists for years: How does dietary restriction produce protective effects against aging and disease? And the reverse: how does overconsumption accelerate age-related disease?...How the diet is restricted -- whether fats, proteins or carbohydrates are cut -- does not appear to matter. "It may not be about counting calories or cutting out specific nutrients," said Dr. Mobbs, "but how a reduction in dietary intake impacts the glucose metabolism, which contributes to oxidative stress." Meanwhile, a high calorie diet may accelerate age-related disease by promoting oxidative stress... Dietary restriction induces a transcription factor called CREB-binding protein (CBP), which controls the activity of genes that regulate cellular function. By developing drugs that mimic the protective effects of CBP -- those usually caused by dietary restriction -- scientists may be able to extend lifespan and reduce vulnerability to age-related illnesses...."We discovered that CBP predicts lifespan and accounts for 80 percent of lifespan variation in mammals," said Dr. Mobbs. "Finding the right balance is key; only a 10 percent restriction will produce a small increase in lifespan, whereas an 80 percent restriction will lead to a shorter life due to starvation."...The team found an optimal dietary restriction, estimated to be equivalent to a 30 percent caloric reduction in mammals, increased lifespan over 50 percent while slowing the development of an age-related pathology similar to Alzheimer's disease..."We showed that dietary restriction activates CBP in a roundworm model, and when we blocked this activation, we blocked all the protective effects of dietary restriction," said Dr. Mobbs. "It was the result of blocking CBP activation, which inhibited all the protective effects of dietary restriction, that confirmed to us that CBP plays a key role in mediating the protective effects of dietary restriction on lifespan and age-related disease."...Researchers examined mice and found that diabetes reduces activation of CBP, leading Dr. Mobbs to conclude that a high-calorie diet that leads to diabetes would have the opposite effect of dietary restriction and would accelerate aging...Dr. Mobbs hypothesizes that dietary restriction induces CBP by blocking glucose metabolism, which produces oxidative stress, a cellular process that leads to tissue damage and also promotes cancer cell growth. Interestingly, dietary restriction triggers CBP for as long as the restriction is maintained, suggesting that the protective effects may wear off if higher dietary intake resumes. CBP responds to changes in glucose within hours, indicating genetic communications respond quickly to fluctuations in dietary intake..."