A workaround to immortality
They tried to treat old age with hydrogen sulfide
Alexey Aleksenko, Forbes, 09.08.2018
Researchers from the University of Exeter have found that if you carefully deliver a little hydrogen sulfide to the right point inside the cell, you can double slow down the aging process.
Modern theories of aging (and, unfortunately, there are so many of them that most will inevitably turn out to be incorrect) can be conditionally divided into two groups. Theories of the first type proceed from the fact that aging is the result of natural deterioration of cells under the influence of environmental factors or the inexorable passage of time. If this is the case, then in order to save yourself from old age, you just need to learn how to protect your body from these factors.
Another group proceeds from the fact that aging is programmed: those very environmental factors do not just spoil the cell, but trigger built-in mechanisms in it that do not allow the suffering cell to spoil the life of the rest of the body. The overall result of the action of such cellular mechanisms throughout life is aging. If this is indeed the case, we have a chance to intervene in the work of these mechanisms in such a way as to optimize their work for the sake of our happy longevity. Perhaps some prospects for such a development are opened by the work of scientists from the University of Exeter (UK), which describes an elegant way to prolong the life of endothelial cells – those that line our blood vessels from the inside.
In the last century, the minds of gerontologists were possessed by an idea belonging to the first group – the free-radical theory of aging by Denham Harman. It is she who still encourages some people to take large doses of vitamin E and other antioxidants, although their uselessness in prolonging life is quite convincingly established. According to Harman's idea, the hottest point of a cell, on which its lifespan depends, is the mitochondria, an energy station where oxygen burns nutrients. An electric field of the same intensity occurs on the mitochondrial membrane as in the lightning channel. A by–product of the process are the very free radicals, that is, spoiled molecules, for the sake of combating which it was once customary to take antioxidants. But if the free-radical theory of aging itself has been comprehensively criticized, then no one questions the key role of mitochondria in this process.
It is there, in the mitochondria itself, that the substances used by British biochemists penetrate. There they emit hydrogen sulfide – the same gas that is released during rotting. They allocate it, however, very carefully and little by little. The result is quite clear: the number of aging (that is, stopped dividing) cells in the culture is halved.
The idea of delivering something useful directly into the mitochondria is not new: this approach, for example, is used in the so-called "Skulachev ions", gerontological preparations based on which the Russian company Mitotech develops. The agent used by English biochemists, in fact, is itself a typical "Skulachev ion" – it contains the same positively charged phosphonium residue, which, according to the idea of academician Vladimir Skulachev, easily pierces directly into the negatively charged pulp of the mitochondria. However, there is a significant difference. The substance that our Russian Skulachev ions deliver is again an antioxidant, albeit intended for a point action. But with hydrogen sulfide, which is delivered by the drugs proposed by the British, everything is much more complicated.
Most popular scientific reports about this work said that hydrogen sulfide inside the mitochondria becomes fuel, that is, it is oxidized by oxygen or the notorious free radicals. In fact, the authors of the article emphasize that the concentration of this substance is too small for such an action. Scientists do not yet know exactly what hydrogen sulfide does inside the mitochondria. But they express certain ideas: in their opinion, sulfide modifies mitochondrial proteins – those that carry a signal to the host cell that something is wrong in the mitochondria, and force it to stop dividing.
This is only a hypothesis; but what happens next is a firmly established fact. In the cells treated with the drug, the number of two proteins called "splicing factors" increases, it depends on them which products the cell will synthesize based on the information recorded in its genes. Researchers have shown that if these splicing factors are removed, the anti-aging effect immediately disappears. It means that the cell's choice of a development program depends on them: whether to consider yourself healthy or to give up on yourself and stop sharing forever.
The picture emerges as follows: hydrogen sulfide slightly changes one of the mitochondrial proteins, which signals about its health; the protein transmits an optimistic signal to the cell nucleus through intermediaries, triggering the production of splicing factors, and they already make it clear to all cellular processes that it is too early to age. Let's recall two groups of theories of aging: obviously, the results of English biochemists not only testify in favor of the second group of theories (that is, programmed old age), but also indicate at which points we can try to influence cellular processes in order to make them work for us.
Of course, the substances developed by English researchers will serve as a direct prototype for the development of pharmacological drugs: a lot of diseases are based on the processes of cellular aging. However, an equally important result is the identification of a key component of cellular processes that cause the cell to age and die. From which side other scientists will approach them, it is impossible to predict yet. But it is obvious that no chance to interfere with nature will be missed: still, living longer is a very tempting prospect.
Maxim Skulachev, CEO of Mitotech, comments:
– The desire of English colleagues to make a competitor to our SkQ is quite understandable, and we welcome it in every possible way. It is gratifying that they also use "Skulachev ions", although, in fact, how else to deliver something to the mitochondria?
This work fully confirms our observations that the delivery of an antioxidant to the mitochondria prevents aging. Colleagues are trying to suggest a slightly different approach, questioning the antioxidant mechanism of hydrogen sulfide action. In my opinion, the data presented in the paper is not enough for such a conclusion. We also have ultra-small dosages of the substance: the fact is that mitochondria, like pumps, accumulate "Skulachev ions" inside themselves, which include Exeter drugs.Nevertheless, we are also inclined to think that the decrease in the number of radicals in mitochondria is also regulatory in nature. That is, as the British suggest, it is not the protection against free radicals itself that is important, but rather a signal: "Everything is young here in our mitochondria, in perfect order."
As for the conclusions about the participation of splicing factors in the process, it seems to me that they are a little premature. Splice factors are very high-level commanders that affect hundreds of different genes. The fact that the removal of these factors has changed the picture of aging regulation may simply be due to the disorder in intracellular affairs.
In general, the results of the British are quite consistent with our ideas about aging. I would venture to say that in some ways we may be many years ahead of them, and I foresee the difficulties they will face when developing the drug. Nevertheless, I sincerely wish them success.
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