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Sirtuin Research Continues Ever Onward in Search of Relevance

As a result of failed commercial efforts a decade ago, research into sirtuins - particularly SIRT1 - in the context of aging is broader than it might otherwise be, and has a great deal of inertia. A lot of funding poured into this area, and as a result efforts to map all of the biochemistry that touches upon SIRT1 continue today, long after the goal of building a therapy to slow aging based upon manipulating SIRT1 was abandoned. The early evidence for SIRT1 to be important enough in aging to be a basis for therapies was demolished, no useful treatment ever emerged, a bunch of investors nonetheless made a very large profit, and the "anti-aging" marketplace continues to sell useless supplements hyped on the basis of sirtuin-related expectations long since shown to be wrong.

Since the primary goal of the scientific community is to gather knowledge, and the one concrete outcome of the sirtuin hype was a foothold of new knowledge in this tiny slice of metabolism, research into sirtuins continues. Since researchers are better able to raise funding when they can offer at least the prospect of application of their research, even when the real goal is only the accumulation of knowledge, sirtuin researchers tend to explain their work in terms of potential impact on aging. But I think that ship has sailed. One should read SIRT1 research nowadays as a matter of interest, an example of the research community making slow progress in building the grand map of how exactly aging functions in detail. That is, sadly, of little relevance to the construction of effective therapies, which can be achieved by bypassing all of that detail to focus on repairing the known root causes of aging, and worrying about how exactly they generate aging in detail further down the line.

A study by researchers reveals that an anti-aging protein can be targeted to rejuvenate cells in the immune system. The protein in question is called SIRT1. The scientists found that it is involved in how cells in the immune system develop with age. They wanted to find out how this anti-aging protein affects a specific category of immune cells known as cytotoxic T cells. These cells are highly specialized guardians of the immune system and their role is to kill cells infected by a virus, damaged cells, or cancer cells.

"Over the course of a person's life, with repeated exposure to bacteria and viruses, these T cells mature and eventually lose a protein called CD28. And as these cells get older, they become more toxic to their environment." This aging process is accelerated by persistent viral infections, such as HIV and cytomegalovirus. In fact, HIV-infected patients accumulate mature cytotoxic T cells at a much younger age than an uninfected person.

When a young (or naive) T cell is in a resting state, it uses oxygen to "breathe". Once it is activated to defend the body against a bacteria or virus, it shifts into enhanced glycolysis and uses sugar to get an immediate boost in energy. This is useful to jump into action, but it isn't sustainable for long-term performance. As the cells age and lose CD28, they can shift into glycolysis much more quickly if breathing is inhibited. They also lose the anti-aging protein SIRT1. This becomes a problem, as it makes them more toxic to the cells around them.

"We studied human T cells, isolated from blood donors of all ages, to compare mature cytotoxic T cells with naive ones." The researchers found that naive T cells have a high concentration of SIRT1. This stabilizes an entire mechanism that prevents the cells from entering glycolysis to use sugar as an energy source, and limits their toxic effects. As the cells age, they lose SIRT1, which changes their basic metabolism. They can then rapidly shift into glycolysis and start producing more toxic proteins called cytokines, which could lead to inflammatory diseases.

Link: https://gladstone.org/about-us/press-releases/anti-aging-protein-could-be-targeted-rejuvenate-immune-cells

Comments

Reason: I was just wondering what some of the "useless anti-aging supplements related to SIRT1 activity" we should avoid. I supplement with NAD+ cell regenerator, melatonin, DHEA, and various herbals, but I do not wish to buy any useless supplements. I also looked up a SIRT1 study of SIRT1 on mice that sounded somewhat encouraging. The reference is Satoh, Cell Metabolism, 2013, SIRT1 extends life span and delay aging in mice. They overexpressed SIRT1 in the hypothallmus and found lifespan extension of 16% in female mice and 9% in males. Not too impressive, but one of the benefits they attributed to SIRT1 overexpression was sleep quality (restored circadian rhythms), which many human suffer from and no doubt increases faster aging, when we desperately want to slow aging.

Posted by: Biotechy at December 2nd, 2017 7:49 AM

Reason: Never mind a response to my above comment. I just found a very extensive review article on Sirtuins by Grabowska, (March 2017) in Biogerontology titled: Sirtuins, a primary target of slowing down the aging process.

Posted by: Biotechy at December 2nd, 2017 1:29 PM

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