Summary: Supplementation with the amino acid D-serine helped to attenuate some of the age-related changes associated with a decline in the hypothalamic hormone Menin in mouse models.
Source: OLP
Decline in hypothalamic menin may play key role in aging, new study suggests PLOS Biology by Lige Leng of Xiamen University, Xiamen, China, and colleagues.
The results reveal a previously unknown physiological aging factor and suggest that supplementation with a single amino acid may attenuate certain age-related changes.
The hypothalamus has been recognized as a key mediator of physiological aging, through an increase in the neuro-inflammatory signaling process over time. In turn, inflammation promotes multiple age-related processes, both in the brain and at the periphery.
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.
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About this aging research news
Author: Claire Turner
Source: OLP
Contact: Claire Turner – PLOS
Picture: Image is in public domain
Original research: Free 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 ultimately death. The molecular mechanisms behind the 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 an important role in neuroinflammation and brain development. Here, we found that hypothalamic Menin signaling decreased in aged mice, which correlates with systemic aging and cognitive deficits.
Restoration of menin expression in the ventromedial nucleus of the hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and enhanced biomarkers of aging, while inhibiting menin in VMH of middle-aged mice induces premature aging and accelerated cognitive decline. We further discovered that Menin epigenetically regulates neuro-inflammatory and metabolic pathways, including D-serine metabolism.
Age-associated Menin reduction led to impaired D-serine release from the 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 age-related cognitive decline.