20 December 2013

A new (and reversible!) the cause of aging

Researchers at Harvard University Medical School, the US National Institute of Aging and the University of New South Wales (Sydney, Australia), working under the guidance of Professor David Sinclair, have found a previously unknown cause of mammalian aging. Moreover, they demonstrated how to eliminate this cause and reverse the aging process.

The essence of the studied mechanism is that the aging processes of the body are accelerated when the interaction between the nucleus and mitochondria is disrupted, carried out through a cascade of molecular mechanisms. At the same time, experiments on aging mice have shown that this interaction can be restored using a compound synthesized by the human body.

Mitochondria are often called the "powerhouses" of a cell, as they generate the chemical energy needed to perform its biological functions. The functioning of these organelles, which have their own membrane and a small genome of their own, has long been recognized as a key biological factor in the aging process. The decay of mitochondrial functions that occurs with aging leads to the gradual development of age-related diseases, such as Alzheimer's disease and diabetes mellitus.

In general, experts are skeptical about the idea of the possibility of reversing the aging process, since, according to the generally accepted hypothesis, age-related diseases are the result of the appearance of mutations in mitochondrial DNA that cannot be restored.

David Sinclair's group has been studying the fundamental aspects of aging for many years, which is traditionally defined as the gradual extinction of body functions over time. The main object of their research is a group of genes encoding sirtuin proteins. In earlier work, they showed that one of these genes, SIRT1, is activated by resveratrol, a natural compound found in grapes, red wine and some types of nuts.

One of the employees of the Sinclair laboratory, Ana Gomes, studied mice with the SIRT1 gene removed. As expected, these animals showed signs of premature aging, including mitochondrial dysfunction. However, to the surprise of the researchers, it turned out that their cells had a normal amount of most mitochondrial proteins encoded by nuclear DNA. Only the levels of proteins encoded by mitochondrial DNA were reduced. This observation was contrary to the data available in the literature.

The search for the underlying causes of the revealed phenomenon led scientists to a complex cascade of mechanisms, starting with the compound nicotinamide-adenine-dinucleotide (NAD), and ending with a molecule that carries information and coordinates the interaction between the nuclear and mitochondrial genomes. Maintaining the right balance in this interaction is the key to cell health. The SIRT1 protein in this signaling cascade plays the role of an intermediary or a kind of guard preventing interference in the process of a molecule known as hypoxia-induced factor-1 (hypoxia-inducible factor 1, HIF-1).

For reasons unclear to date, the amount of NAD in the body decreases with age. Under conditions of lack of NAD, SIRT1 loses the ability to block HIF-1 activity. The concentration of HIF-1 increases, which introduces an imbalance in the intergenomic interaction. Over time, this leads to a decrease in the ability of the cell to produce energy, which at the organizational level causes the appearance of signs of aging and associated diseases.

Further experiments have shown that the introduction of an endogenous compound, which is a precursor of NAD, restores the disturbed mechanism, which entails the restoration of inter-genomic interaction and mitochondrial function. With timely intervention – before the accumulation of a large number of mitochondrial DNA mutations – this allows you to eliminate some of the consequences of the aging process.

The analysis of the muscle tissue of two-year-old mice, which were injected with the NAD precursor for a week, demonstrated that parameters such as insulin resistance, inflammatory status and atrophy of muscle tissue corresponded to the indicators obtained by analyzing the tissues of six-month-old animals. In terms of human age, this corresponds to the return of the muscles of a 60-year-old person to the condition of a 20-year-old, at least with respect to the listed parameters.

Of particular interest is the fact that the HIF-1 molecule is involved in disrupting the interaction between the nucleus and mitochondria, which is usually activated under conditions of oxygen starvation. Under normal conditions, HIF-1 is in an inactive state. However, it is known that this compound is active in malignant cells and several groups of researchers are studying its role in the formation of tumors.

Currently, the authors are studying the long-term effects of the introduction of a precursor OVER mice, as well as the effect of this compound on the state of the animal organism as a whole. They are also considering using it to treat mitochondrial diseases and more common diseases such as type 1 and type 2 diabetes. In the long term, Sinclair plans to test whether this compound can provide mice with a longer and healthier life.

Article by Ana P. Gomes et al. Declining NAD Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging is published in the journal Cell.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from Harvard Medical School: A New—and Reversible—Cause of Aging.

And now – a fly in the ointment from another source, from the portal news.com.au (University of NSW research finds compound that can reverse aging). The endogenous precursor of NAD is nicotinamide mono nucleotide (nicotinamide mononucleotide, NMN), which the researchers injected into mice daily at the rate of 500 mg per kilogram of weight. Mouse.  In the Sigma-Aldrich catalog, these 500 mg cost 1,315 euros. True, it is not available now, but if you search, you will find it. Perhaps cheaper: in the Australian news they call a very ridiculous price, $ 1000 for a whole gram. So you can not wait for the end of clinical trials (if it comes to them in connection with the above financial difficulties at all) and try to self-medicate. Just first estimate your weight and the thickness of your bank account. Taking into account the fact that the duration of the effect of the weekly course is still unknown and, perhaps, it will have to be repeated once a month.


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