Scientists have pinpointed a single protein in the ventromedial hypothalamus, menin, that appears to act as a brake on the whole-body aging process. In mice, natural levels of menin fall as the animals grow older. When researchers restored the protein in the brain of elderly mice, the animals showed thicker skin, stronger bones, sharper memory and a modest extension of lifespan; shutting the gene off in middle-aged mice triggered the opposite pattern, with faster physical and cognitive decline.
Menin seems to work by dampening NF-κB–driven inflammation and by encouraging production of the neurotransmitter D-serine. Supplementing aged mice with D-serine alone partly rescued memory loss, suggesting the amino acid is one downstream lever through which menin protects the brain.
Because chronic, low-grade inflammation is already linked to many age-related diseases, the study positions menin as a master switch connecting genetic, inflammatory and metabolic drivers of aging. The authors caution that translating the finding to people will require new tools to raise menin safely in the human brain; for now, lifestyle strategies that quell systemic inflammation, exercise and balanced diets low in saturated fat—remain the surest path to healthy aging.
Hypothalamic Menin regulates systemic aging and cognitive decline – 16 March 2023
Abstract: “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.”
EurekAlert! – “Loss of Menin helps drive the aging process, and dietary supplement can reverse it in mice” – 16 March 2023
Cognition, bone mass, skin thickness, and lifespan all affected by Menin’s decline.
Press summary of the PLOS Biology paper emphasising that menin decline fuels whole-body aging in mice and that D-serine supplementation can counter cognitive decline.
Genetic Engineering & Biotechnology News – “Hypothalamic Protein Loss Drives Aging, Hints at Approach to Reverse Cognitive Decline” – 17 March 2023
Explains how restoring menin extended lifespan and improved multiple aging markers, framing the protein as a potential therapeutic target to slow physiological aging.
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