Sirtuins preserve not only youth, but also reason?

The developers of geroprotectors drew attention to sirtuins in 1999, when Leonard Guarente, a biologist from the Massachusetts Institute of Technology, showed that yeast with extra copies of the gene encoding the enzyme Sir2 is able to divide much more times than the cells of ordinary yeast. By now, the fact that sirtuins in a variety of species of living beings, from yeast to rodents, (due to the activation of the same mechanisms as with a lifelong low–calorie diet, but without its side effects) are able to counteract aging is no longer a hypothesis, but an almost universally accepted theory in the scientific world.

Whether it will be possible to use this theory to create a "pill for old age" is still unknown, but two drugs based on low–molecular substances that stimulate the synthesis of sirtuins are already undergoing phase II clinical trials: one as a cancer treatment, and both as drugs for type II diabetes. The third of these drugs has so far been tested only on animals. Now it is also positioned as a future cure for diabetes, but its potential effect seems to be wider.

Now a group of researchers from the same MIT led by Li-Huei Tsai has discovered that sirtuin-1 (in humans, this protein is encoded by the SIRT1 gene) also affects brain function, especially learning and memorization processes.

In 2007, Tsai and her colleagues showed that sirtuins are able to protect neurons from neurodegenerative processes and contribute to improving learning and memory, but then the researchers believed that this was simply a byproduct of protecting neurons from oxidative and inflammatory stress.

Now scientists have established that sirtuins are directly involved in the regulation of so-called synaptic plasticity – the ability of neurons to strengthen or weaken connections with each other. This process is critically important in the formation of long-term memory. The mechanism of action of sirtuins in this case consists in the fact that these proteins block the activity of miR-134 microRNA, which, in turn, stops the synthesis of the regulatory protein CREB (cAMP response element-binding protein, cAMP–dependent binding protein). This protein "includes" a number of genes and, obviously, is the central link of various ways of forming interneuronal connections.

Article by Jun Gao et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134 was published in the on-line issue of Nature on July 11, 2010.

The next stage of research is a detailed study of the mechanisms of the effect of SIRT1 on the functions of neurons and the study of other effects besides the effect on memory and learning, which may manifest as a result of the activation of the expression of SIRT1 genes in brain cells and other tissues.

Perhaps the knowledge gained will allow us to create new drugs that can fight Alzheimer's disease and other neurodegenerative diseases.

Portal "Eternal youth" http://vechnayamolodost.ru based on MIT materials: Protein linked to aging may boost memory and learning ability15.07.2010