Starve yourself and live longer

Researchers at Mount Sinai School of Medicine have unraveled a molecular puzzle to reveal why a lower-calorie diet slows the development of some age-related conditions such as Alzheimer’s disease, as well as the aging process itself. In their search for an answer they discovered that it doesn’t seem to matter how the diet is restricted – whether fats, proteins or carbohydrates are cut – to produce protective effects against aging and disease.

A two-part study led by Charles Mobbs, PhD, Professor of Neuroscience and of Geriatrics and Palliative Medicine at Mount Sinai School of Medicine, indicates that a reduction of dietary intake blocks a person’s glucose metabolism, which contributes to oxidative stress - a cellular process that leads to tissue damage and also promotes cancer cell growth. Conversely, 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.
The first part of the study looked at c. elegans, a species of roundworm, that were genetically altered to develop Alzheimer’s disease-like symptoms. Dr. Mobbs and his team reduced the roundworms’ dietary intake by diluting the bacteria the worms consume. They found that when dietary restriction was maintained throughout the worms’ adulthood, lifespan increased by 65 percent and the Alzheimer's disease-related paralysis decreased by about 50 percent.
In the second part of study, Dr. Mobbs and his team looked at the other end of this process: What happens to CBP in a high-calorie diet that has led to diabetes, a disease in which glucose metabolism is impaired? 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.
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,” said Dr. Mobbs. “If we can map out these interactions, we could then begin to produce more targeted drugs that mimic the protective effects of CBP.”

New 3D Imaging technology promises early detection of Alzheimer’s and Dementia

The older people become, the greater risk they have of sharing the tragic fate of those who remain alive yet are increasingly unaware of the world around them. In industrialised countries, one to six percent of the population over the age of 65 and an even more alarming ten to twenty percent over the age of 80 suffer a progressive loss of their cognitive abilities. Alzheimer disease is the most common cause, affecting 50 to 60 percent of all cases, followed by circulatory disorders in small blood vessels, capillaries and venules (calcifications), which make up about 20 percent. These disorders cause ever larger parts of the brain to become necrotic due to an insufficient supply of blood.

The earlier these disorders and their causes are detected, the more effective the therapies can be for preventing the disease or at least substantially slowing down its progress. Increasingly higher-resolution imaging techniques making major contributions to early detection are now being presented at the European Congress of Radiology (ECR 2007), held in Vienna from March 9 to 13, 2007, and attended by some 16,000 participants from 92 countries. University Professor Dr. Daniela Prayer from the Clinical Department for Neuroradiology at the Vienna University of Medicine states, “Although we cannot yet depict individual cells, we can image ultra-tiny bundles of fibre with high resolution. That is a spectacular breakthrough!”
Voxel-based morphometry allows for the volume of grey matter and white matter in the brain to be determined to the nearest cubic millimetre.
A reduction in brain mass (atrophy) in certain areas indicates Alzheimer’s disease and in other areas, other forms of dementia, according to Professor Prayer. An MR study by Professor Dr. Riccardo della Nave and his colleagues at the University of Florence, for instance, found that certain degenerative phenomena occurring in the left thalamus and in a zone in the left cerebral cortex are the first signs of family-related Alzheimer’s disease. “These findings are quite valuable. They enable us not only to differentiate precisely but also to detect the patterns of the disease before symptoms even occur and to check the efficacy of new drugs, namely, whether they can really stop the loss of brain mass.”
Another advance allows insights into the circuitry architecture of individual bundles of cerebral fibre. It is based on special techniques applicable with modern magnetic resonance devices to render visible the movements of water molecules in the space between fibres. Professor Prayer explains, “Wherever protons change direction, there has to be an obstacle, a cell wall or a fibre connection. Applying the reverse conclusion, we obtain a picture of these structures and see early on where swelling occurs or cells die off.”
No less fascinating are the prospects opened up by magnetic resonance spectroscopy (MRS). It allows a non-contact x-ray view of biochemical processes within the regions of the brain under examination.
All in all, Professor Prayer notes, “the new methodological advances of magnetic resonance technology provide us with a hopeful view of the future in terms of the early diagnosis and efficacy testing of therapies for dementias. If this happens in the near future, the spectre of old-age dementia will lose much of its threatening effect.”