Unlocking the Fountain of Youth: Dietary Supplement Reverses Aging by Countering Menin Loss

Summary: Supplementing the amino acid D-serine helped to mitigate some of the age-related changes associated with a decline of the hypothalamic hormone Menin in mouse models.

Source: PLOS

Decline in the hypothalamic Menin may play a key role in aging, according to a new study in PLOS Biology by Lige Leng of Xiamen University, Xiamen, China, and colleagues.

The findings reveal a previously unknown driver of physiological aging, and suggest that supplementation with a simple amino acid may mitigate some age-related changes.

The hypothalamus has been recognized as a key mediator of physiological aging, through an increase in the process of neuroinflammatory signaling over time. In turn, inflammation promotes multiple age-related processes, both in the brain and the periphery.

Recently, Leng and colleagues showed that Menin, a hypothalamic protein, is a key inhibitor of hypothalamic neuroinflammation, leading them to ask what role Menin may play in aging. Here, they observed that the level of Menin in the hypothalamus, but not astrocytes or microglia, declines with age.

To explore this decline, they created conditional knockout mice, in which Menin activity could be inhibited. They found that reduction of Menin in younger mice led to an increase in hypothalamic neuroinflammation, aging-related phenotypes including reductions in bone mass and skin thickness, cognitive decline, and modestly reduced lifespan.

Another change induced by loss of Menin was a decline in levels of the amino acid D-serine, known to be a neurotransmitter and sometimes used as a dietary supplement found in soybeans, eggs, fish and nuts. The authors showed this decline was due to loss of activity of an enzyme involved in its synthesis (which was in turn regulated by Menin).

Could reversing age-related Menin loss reverse signs of physiological aging? To test that, the authors delivered the gene for Menin into the hypothalamus of elderly (20-month-old) mice.

Thirty days later, they found improved skin thickness and bone mass, along with better learning, cognition, and balance, which correlated with an increase in D-serine within the hippocampus, a central brain region important for learning and memory.

This shows a brain
Researchers find that the loss of a hypothalamic hormone helps drive the aging process, and a supplement can help reverse it in mice. Image is in the public domain

Remarkably, similar benefits on cognition, though not on the peripheral signs of aging, could be induced by three weeks of dietary supplementation with D-serine.

There is much left to be learned about Menin’s role in aging, including the upstream processes that lead to its decline, and there is much to learn about the potential for exploiting this pathway, including how much phenotypic aging can be slowed, and for how long, and whether supplementation with D-serine may trigger other changes, yet to be discovered.

Nonetheless, Leng said, “We speculate that the decline of Menin expression in the hypothalamus with age may be one of the driving factors of aging, and Menin may be the key protein connecting the genetic, inflammatory, and metabolic factors of aging. D-serine is a potentially promising therapeutic for cognitive decline.”

Leng adds, “Ventromedial hypothalamus (VMH) Menin signaling diminished in aged mice, which contributes to systemic aging phenotypes and cognitive deficits. The effects of Menin on aging are mediated by neuroinflammatory changes and metabolic pathway signaling, accompanied by serine deficiency in VMH, while restoration of Menin in VMH reversed aging-related phenotypes.”

Article title created with ChatGPT AI technology

About this aging research news

Author: Claire Turner
Source: PLOS
Contact: Claire Turner – PLOS
Image: The image is in the public domain

Original Research: Open access.
Hypothalamic Menin regulates systemic aging and cognitive decline” by Lige Leng et al. PLOS Biology


Abstract

Hypothalamic Menin regulates systemic aging and cognitive decline

Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling.

Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits.

Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism.

Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice.

Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.

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  1. Well, why don’t you be the first one to volunteer to die then so the population is smaller? I think someone idolized Bill Gates too much. Interesting that people in biblical times lived hundreds of years. It is not that the planet is overpopulated. We are densely colsolidated into certain area mainly caused by the industrial revolution. And our governments underutilized resources and or waste them. Poison our water and modify the weather with clouding seeding and other methods. The earth was perfectly created by God to balance itself. Climate change is nothing other than the earth attempting to do so. If humans would stop playing god and messing with everything that could maybe happen. But planting more trees and using sustainable and regenerative agricultural never seems to cross anyone’s mind. Be a good human and live within your means, minimize waste, plant a garden and some trees, and be nice to people.

    1. Thanks for being as nutty as a squirrel turd. We appreciate you using your great experience in nutrition in the same vein we would call SpongeBob Square Pants a Marine Biologist.

  2. It is nice it it helps some people with memory issues. But, the world is increasingly overpopulated with people that live longer than nature intended. This is causing us to use resources much too quickly and lessen the sustainance of Life on the planet for generations to come. Overall, not good for the general public.

    1. Really Kate? It might be better to approach a solution to sustaining the earth. I believe that my children and grandchildren are worth living for.

    2. 1970s thinking. Nature does not “intend”. And we violate nothing, improving our lives. If nature intended anything, it was for organisms to chose to flourish, and meet their needs, seeking high and low to do so.
      Population increases, but we have the means to limit our impact to below levels in the 1800s, without compromising, and rather enhancing, quality of life. Greenhouse technology, fish farming, and other technologies can return 3/4 of farmland to the buffalo. Nuclear, geothermal, Hydroelectric, tidal and solar, can provide beyond an order of magnitude more energy than we currently use powering chemical syntheses, and the refinement of titanium and other more useful, durable building blocks of infrastructure. Nutrients can be recycled rather and discarded in the rivers. Mining can be done with robotics, and tailings compacted and returned. Greenhouses can grow plants without pesticides and all the other -cides. Vehicles can operate on electricity, and very large vehicles can operate nuclear–electric, chaperoning other smaller vessels and aircraft, periodically charging them in motion. We may still use petroleum for tires, and other materials, or even engineer that away. Wood can be synthesized, so can any number of other organism-based materials, chemically, and printed to provide characteristics unavailable in nature. Water can be recycled, and is already in places. The only thing theoretical about this is scale…and that is vision, public will and politics driven. We would be there today, if there had not been such a strong antinuclear movement, neurotic elevation of a past that never was, and the interests/greed of big oil, the farm lobby, utilities and military contractors.
      Have you lived long enough to see the polluted rivers run blue again, and the air go from brown to clear? That happened, all the while, population was growing. One is not a function of the other.

    3. Kate
      You seem like a total idiot with your comment.
      You state longevity is not appropriate.
      Sincerely, you are irrational.

    4. Covid and the vaccine is taking care of overpopulation. This is about improving quality of life and treatment. So if you had a loved one with Dementia you wouldn’t want to help them? How bout for yourself? You’re worried about overpopulation!? I’d prefer to live longer to enjoy life, family, and friends

    5. Kate, first off, nature doesn’t determine life… God does. Second, what is your educational background and research to back up your statement?

    6. I feel what you’re saying. Science is interesting, but isn’t there something to be said for “ as nature intended”? Ultimately death is what gives our lives value and meaning. Why do people get preoccupied with wanting to live forever, with not wanting to accept the idea of a time limit, a constraint that challenges you to do the thing or not: the clock is ticking!

    7. Yeesh. I have seen the decline of many loved ones and not even one would make me feel that they are used up – that they have breathed enough of our air.

    1. One goes to Amazon or Iherb or any number of other online or brick and mortar stores and orders it or buys it. I have a half-pound of it in my hand, made by nutricost. Tastes sweet initially then very quickly a bit bitter, when I put some on my tongue. When they say “supplement”, they mean take a “dietary supplement”. I mix it with milk generally, along with glycine for joints and betaine (TMG), and a bit of Nesquik and stevia for taste. But you can take it any way you like.

      1. Just to be clear Mindbreaker is talking about L-serine supplements. L-serine Is converted into d-serine in thd body. The actual study on rats used d-serine dissolved into their water. D-serine is very difficult to find and is expensive. The study used d-serine from Sigma Aldrich product #S4250. $47 USD for 5g.

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