Menin’s decline in the hypothalamus may contribute to physiological aging, affecting cognition, bone mass, skin thickness, and lifespan. A recent study using mice suggests that a simple dietary supplement of one amino acid can help alleviate some of these age-related changes.
The loss of Menin helps to speed up the aging process and a dietary supplement can reverse it in mice.
Cognition, bone mass, skin thickness, and lifespan are all affected by Menin decline.
According to a new scientific study, the drop in hypothalamic Menin could play a key role in aging. The results reveal a previously unknown physiological aging factor and suggest that supplementation with a simple amino acid 
Researchers have found that the loss of a hypothalamic hormone helps to speed up the aging process and that a supplement can help reverse it in mice. Credit: Lige Leng, Ziqi Yuan and Jie Zhang, 2023, PLOS Biology, CC-BY 4.0
Recently, Leng and his colleagues showed that Menin, a hypothalamic protein, is a key inhibitor of hypothalamic neuroinflammation, leading them to wonder what role Menin might play in aging. Here they observed that the level of Menin in the hypothalamus, but not astrocytes or microglia, decreases with age. To explore this decline, they created conditional knockout mice, in which Menin activity could be inhibited. They found that reducing Menin in younger mice led to increased hypothalamic neuroinflammation, aging-related phenotypes including reductions in bone mass and skin thickness, cognitive decline, and life span. slightly reduced life.
Another change induced by the loss of Menin was a drop in levels of the amino acid D-serine, known to be a neurotransmitter and sometimes used as a dietary supplement found in soy, eggs, fish, and nuts. The authors showed that this decrease was due to the loss of activity of an enzyme involved in its synthesis (itself regulated by Menin).
Could reversing age-related Menin loss reverse the signs of physiological aging? To test this, the authors introduced the Menin gene into the hypothalamus of aged mice (20 months). Thirty days later, they saw an improvement in skin thickness and bone mass, as well as better learning, cognition, and balance, which correlated with an increase in D-serine. in the hippocampus, a central region of the brain important for learning and memory. Remarkably, similar benefits on cognition, but not on peripheral signs of aging, could be induced by three weeks of dietary D-serine supplementation.
Much remains to be learned about Menin’s role in aging, including the upstream processes that lead to its decline, and there is much to be learned about the potential for harnessing this pathway, including to what extent aging phenotypic can be slowed down and for how long. , and whether D-serine supplementation can trigger other changes, yet to be discovered.
Nevertheless, Leng said, “We speculate that the decline in Menin expression in the hypothalamus with age may be one of the driving factors of aging, and Menin may be the key protein linking genetic, inflammatory factors and metabolism of aging. D-serine is a potentially promising therapy for cognitive decline.
Leng adds, “Menin signaling in the ventromedial hypothalamus (VMH) was decreased in aged mice, contributing to systemic aging phenotypes and cognitive deficits. Menin’s aging effects are mediated by neuroinflammatory changes and metabolic pathway signaling, accompanied by serine deficiency in VMH, while Menin’s restoration in VMH reversed aging-related phenotypes.
Reference: “Hypothalamic Menin Regulates Systemic Aging and Cognitive Decline” by Lige Leng, Ziqi Yuan, Xiao Su, Zhenlei Chen, Shangchen Yang, Meiqin Chen, Kai Zhuang, Hui Lin, Hao Sun, Huifang Li, Maoqiang Xue, Jun Xu, Jingqi Yan, Zhenyi Chen, Tifei Yuan and Jie Zhang, March 16, 2023, PLoS Biology.
DOI: 10.1371/journal.pbio.3002033