30% fewer calories offers protection against ageing diseases

Researchers at Mount Sinai School of Medicine are close to answering the question that has been challenging scientists for years: How do dietary restriction and the reverse, overconsumption – produce protective effects against ageing and disease?

An answer comes in a two-part study led by Charles Mobbs, Professor of neuroscience and of geriatrics and palliative medicine at Mount Sinai School of Medicine, published in the journal, Public Library of Science Biology.

‘The Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling’, examines how dietary restriction and a high-caloric diet influence biochemical responses.

Professor Mobbs and his colleagues have determined that within certain parameters, a lower-calorie diet slows the development of some age-related conditions such as Alzheimer’s disease, as well as the ageing process. 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, but how a reduction in dietary intake impacts the glucose metabolism, which contributes to oxidative stress,” he said. 

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% of lifespan variation in mammals,” said Professor Mobbs.

“Finding the right balance is key; only a 10% restriction will produce a small increase in lifespan, whereas an 80% restriction will lead to a shorter life due to starvation.”

The team found an optimal dietary restriction, estimated to be equivalent to a 30% caloric reduction in mammals, increased lifespan over 50% while slowing the development of an age-related pathology similar to Alzheimer’s disease.

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.

“Our next step is to understand the exact interactions of CBP with other transcription factors that mediate its protective effects with age,” he explained.

“If we can map out these interactions, we could then begin to produce more targeted drugs that mimic the protective effects of CBP.”