The recipe for prolonging youth: add sirtuin to the hypothalamus
The source of eternal youth was placed in the brain
Adding fuel to the fire was the fact that sirtuin, as his fans claimed, associated life expectancy with moderation in food and wine: the level of this protein increased with a low-calorie diet and with the use of resveratrol contained in wines (however, not only in them). (At the same time, other curious properties were found in sirtuin: for example, it worsened the mood.)
Subsequently, it turned out that sirtuin may have nothing to do with it at all, and life expectancy increases due to concomitant changes in the genome that occur when experimenters manipulate sirtuin. In other words, the effect of sirtuin almost turned out to be an artifact. On the other hand, there were suspicions that everything is not so smooth with wine here, that wine substances affect sirtuin strongly indirectly and only under artificial experimental conditions. The most devoted "fans" of this protein rushed to the rescue – and they managed to show that wine resveratrol still directly affects sirtuin.
However, a more intriguing question – what is the situation with the connection between sirtuin and life expectancy – remained unanswered.
And yet, apparently, the truth here is on the side of the adepts of Sirtuin. A group of researchers led by Shinichiro Imai from Washington University in St. Louis (USA) managed to prove that the level of this protein is indeed associated with both an increase in life expectancy and moderation in food. However, to demonstrate this, scientists had to literally get into their heads: sirtuin showed its remarkable properties while being in the neurons of the hypothalamus.
The scientists worked with mice programmed to overproduce sirtuin. Only some animals had such overproduction throughout the body, while others had it only in certain tissues. So it was found out that in order to increase life expectancy, sirtuin needs to be active in the brain. Moreover, the increase in life span in this case was exactly the same as in ordinary mice on a low-calorie diet. On the other hand, if the level of sirtuin in the brain was increased, the mice could eat anything and anytime: they still lived longer.
The lengthening of life was accompanied by a complex of physiological and behavioral features: the animals were more active at night (that is, when they should be active), their body temperature and oxygen consumption increased, their muscle condition improved, while they slept more soundly during the day. These changes, as well as the increase in life span, affected both sexes – both males and females.
How long has the lifespan of mice been extended? As Mr. Imai and his colleagues write in Cell Metabolism (Satoh et al., Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH), the longevity of females increased by 16%, males by 9%. In terms of human summers, this means that a woman may well live to be a hundred years old, and a man will easily reach eighty.
Scientists also note that mice with elevated sirtuin in the brain were less likely to develop cancer. As for aging, the effect of the protein was that it shifted the moment of starting the aging process, but not its rhythm. That is, aging itself did not slow down, but it began later: sirtuin really corresponds more to the comparison with the "source of youth".
The brain, however, is quite a large organ, even in a mouse, and the researchers tried to determine which area of the brain needs sirtuin to slow down aging.
The search led to the dorsolateral and lateral nuclei of the hypothalamus (the hypothalamus generally takes an active part in the regulation of metabolism, and the lateral nuclei of the hypothalamus, as is known, regulate eating behavior). Sirtuin made neurons more sensitive to orexins, neuropeptide hormones, which again affect metabolism, and also participate in the regulation of the sleep and wakefulness cycle.
However, in this case, according to scientists, the combined action of sirtuin and orexins stimulated the intense signals that the hypothalamus sends to the muscles. These signals cause physiological changes in muscle tissue (although what mechanism allows the hypothalamus neurons to focus so precisely on the muscles, researchers do not yet know), and the slowing down of aging was noticeable primarily in the muscles.
That is, the following scheme turns out: an increased level of sirtuin causes specific activity of some areas of the hypothalamus, directed at muscles that, at the direction of "from above", begin to behave differently: their metabolism changes and aging slows down. And the same thing happens when the body receives only the necessary minimum of calories.
It is not difficult to notice some incompleteness of the explanation here: aging obviously slows down in the whole body, not just in the muscles; in addition, long-lived mice showed complex changes in their physiology. And so one could ask what happens in all the other tissues: whether they receive individual instructions from the brain, or whether changes in muscle metabolism affect other organs as well. However, in any case, researchers can now say that there is indeed a connection between life expectancy and sirtuin.
Prepared based on the materials of Washington University in St. Louis: Aging really is ‘in your head'.
Portal "Eternal youth" http://vechnayamolodost.ru05.09.2013