Scientists from Mount Sinai School of Medicine seemed to have begun to address a question that has been challenging scientists for years that is, how do dietary restriction and the reverse, over consumption produce protective effects against aging and disease? Apparently, the answer lies in a two-part study which analyzes how dietary restriction and a high-caloric diet influence biochemical responses.
The study authors were believed to have unraveled a molecular puzzle to establish that inside definite parameters, a lower-calorie diet slows the growth of some age-related conditions such as Alzheimer’s disease in addition to the aging process. How the diet is restricted i.e. whether fats, proteins or carbohydrates are broken down may not matter. Meanwhile, a high calorie diet could perhaps accelerate age-related disease by encouraging oxidative stress.
“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,” said Lead author of the study, Charles Mobbs, PhD, Professor of Neuroscience and of Geriatrics and Palliative Medicine at Mount Sinai School of Medicine.
Dietary restriction is known to induce a transcription factor called CREB-binding protein (CBP). This CBP supposedly controls the activity of genes that regulate cellular function. Scientists could be able to expand lifespan and decrease susceptibility to age-related illnesses via developing drugs that imitate the protective effects of CBP, those which are typically caused by dietary restriction.
“We discovered that CBP predicts lifespan and accounts for 80 percent of lifespan variation in mammals. 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,” says Dr. Mobbs.
The findings of the study revealed that an optimal dietary restriction seemed to have increased lifespan over 50 percent even as slowing the development of an age-related pathology similar to Alzheimer’s disease. This optimal dietary restriction is estimated to be equal to a 30 percent caloric reduction in mammals.
The first part of the study was noted to have examined C. elegans, a species of roundworm, that were genetically changed in order to develop Alzheimer’s disease-like symptoms. Furthermore, Dr. Mobbs along with his team seemed to have decreased the roundworms’ dietary intake by diluting the bacteria the worms eat.
In these types of roundworms, human beta amyloid peptide is known to be expressed in muscle which becomes paralyzed as age progresses. Also, human beta amyloid peptide supposedly contributes to plaque increase in Alzheimer’s disease. This model was observed to have allowed the authors to eagerly measure how lifespan and disease burden were simultaneously improved by dietary restriction.
The authors found that when dietary restriction was maintained all through the worms’ adulthood, lifespan appeared to have risen by nearly 65 percent. In addition, the Alzheimer’s disease-related paralysis seemed to have decreased by approximately 50 percent.
Dr. Mobbs further said that, “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. 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.”
In the second part of study, Dr. Mobbs along with his team analyzed the other end of this process that is, what happens to CBP in a high-calorie diet that has led to diabetes, a disease in which glucose metabolism is impaired? They were believed to have examined mice and found that diabetes seems to reduce activation of CBP. This leads Dr. Mobbs to conclude that a high-calorie diet that results in diabetes may perhaps have a contradictory effect of dietary restriction and would accelerate aging.
Dr. Mobbs hypothesizes that dietary restriction may possibly induce CBP by blocking glucose metabolism. More so, this glucose metabolism is known to produce oxidative stress, a cellular process that leads to tissue damage and also promotes cancer cell growth.
Amusingly, dietary restriction could trigger CBP for as long as the restriction is maintained. This suggests that the protective effects may possibly wear off if higher dietary intake resumes. Furthermore, CBP seems to respond to changes in glucose within hours thereby indicating that genetic communications respond rapidly to fluctuations in dietary intake.
The authors claimed that the subsequent step is to understand the precise interactions of CBP with other transcription factors that mediate its protective effects with age. If they can map out these interactions then they may perhaps be able to begin to produce more targeted drugs that mimic the protective effects of CBP.
The findings of the study, ‘Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling’ have been published in the journal, Public Library of Science Biology.