Searching for Longevity

Edited by Marino Macchio

Less calories = more memory, SLOWENING OF THE AGING

what emerges from a research on three genes: Sirt1 - Sirt3 - Sirt4

Not only could consuming less caloric meals extend life, but it could also improve memory and cognitive abilities. What emerges from the research on SIRT1, a recently discovered gene that plays an important role in longevity when stimulated by resveratrol (a molecule contained in red wine).

SIRT1, the gene whose activity increases with decreasing calories consumed, demonstrates that in murine models the protein for which it encodes enormously increases the connections between neurons, synaptic plasticity and the formation of memories, reducing the neuro-degeneration and thus preventing the learning difficulties, as the main author of the study, Li-Huei Tsai, of the Howard Hughes Medical Institute pointed out. Recent studies had already linked SIT1 to brain physiology and neurological disorders, but before Tsai's discovery the role of this gene was unknown. Instead, the role of two other genes was known: SIRT3 and SIRT4, both associated with longevity because they are able to protect cells from certain types of stress, such as that of caloric restriction in the presence of which are activated, protecting the cells from diseases of the aging.

Scientists have long known that a low calorie diet prolongs the life of at least a third, but before their discovery they failed to understand what the underlying molecular mechanism was. The answer came from a study by David Sinclair, associate professor of pathology at Harvard Medical School, in collaboration with researchers from the National Institute of Health at Cornell Medical School. The SIRT3 and SIRT4 genes, like SIRT1, are part of a large family of genes, called sirtuins. The discovery of the two new genes confirmed that mitochondria are the primary energy source of cells and are essential for maintaining their health and longevity. When the efficiency of the mitochondria starts to decrease, the energy "comes out" from the cells, which begin to die. Mitochondrial DNA (mtDNA) is so important that even if all the sources of energy within it, including the nucleus, were missing, with the mitochondria remaining viable and functional, the cell would still be able to survive. SIRT3SIRT4 maintain the vitality of mitochondria and therefore make cells healthy.

According to the study, when a diet is started, the cells begin to suffer from caloric restriction and this stressful situation is signaled through the cell membrane. The signal reaches and activates the NAMPT gene and the high concentration of NAMPT, in turn, increases the levels of NAD that accumulates in the mitochondria. This series of reactions causes the mitochondria to grow stronger, increase the emission of energy and the process of cellular aging slows down significantly. This same process is activated by physical exercise.

Sinclair explains: "We are not yet sure of the particular mechanism that is activated by the increase in NAD levels, but we found that when it comes into action, programmed cellular suicide is attenuated. It is the first time that SIRT3 and SIRT4 have been associated with cell survival. According to the researcher, SIRT3 and SIRT4 could become targets for anti-aging drugs and associated diseases.