Scientists may have discovered a hidden biological switch that helps control the rate of aging in the body. Research published in PLOS Biology The study suggests that decreased levels of a brain protein called menin may cause inflammation, memory loss, and other age-related changes throughout the body. In experiments on mice, restoring protein reversed some signs of aging, and simple amino acid supplements improved cognitive function.
The findings add to the growing body of evidence that aging may be strongly influenced by the hypothalamus, a small but powerful brain region that regulates metabolism, hormones, body temperature, sleep, and stress responses. Researchers increasingly believe that the hypothalamus is the central command center of aging itself.
Brain proteins decrease with age
The study, led by Lige Leng of China’s Xiamen University and colleagues, focused on menin, a protein that helps suppress inflammation in the brain. Previous studies had already shown that menin plays an important role in controlling neuroinflammatory activity. The research team wanted to know whether the loss of this protective protein contributes to aging.
Their experiments revealed that menin levels in the hypothalamus decline rapidly as the mice grow. This decrease occurred specifically in neurons within the ventromedial hypothalamus (VMH), a region associated with metabolism and systemic aging. Interestingly, menin levels were not significantly reduced in nearby supporting cells such as astrocytes and microglia.
To investigate what this loss means, researchers generated mice in which menin activity could be selectively reduced. The effect was remarkable. Young mice with lower menin levels developed increased brain inflammation, thinner skin, lower bone mass, impaired balance, memory impairment, and shorter lifespans compared to normal mice.
This result suggests that menin may function as a protective “anti-aging” factor in the brain.
D-serine relationship
One of the most surprising discoveries involved D-serine, an amino acid that also functions as a neurotransmitter in the brain. D-serine helps regulate communication between neurons and is important for learning and memory.
As menin levels decreased, D-serine production also decreased. The researchers found that this effect was due to decreased activity of an enzyme required for D-serine synthesis, which itself appears to be regulated by menin.
D-serine is found naturally in foods such as soybeans, eggs, fish, and nuts, and is also sold as a dietary supplement.
The link caught researchers’ attention because other studies have linked lower D-serine levels to age-related cognitive impairment and decreased synaptic plasticity, the brain’s ability to strengthen neural connections involved in memory and learning.
Reversing signs of aging in mice
The researchers then tested whether restoring menin could reverse age-related decline.
They directly introduced the menin gene into the hypothalamus of aged mice at approximately 20 months of age, which is roughly equivalent to late-life aging in humans. After just 30 days, the animals showed visible improvements in learning, memory, balance, skin thickness, and bone density.
This improvement was accompanied by an increase in D-serine levels in the hippocampus, a brain region essential for memory formation.
The research team also tested whether D-serine supplementation alone had an effect. After three weeks of supplementation, the older mice’s cognitive performance improved, but the treatment did not reverse physical aging markers found in their skin and bone tissue.
This difference suggests that menin may influence aging through several interrelated biological pathways, not just D-serine production alone.
Why the hypothalamus is a major focus of aging research
Interest in the hypothalamus has grown rapidly in recent years as scientists have found evidence that this brain region may regulate many aspects of aging throughout the body.
More recent studies have investigated how age-related changes in hypothalamic DNA methylation and hormone signaling contribute to neurodegenerative diseases such as Alzheimer’s disease. One of the 2024 studies nature communications found that the hypothalamus undergoes unique epigenetic changes with age that may affect pathways involved in oxytocin and gonadotropin-releasing hormone (GnRH), which are associated with aging and brain health.
Taken together, these findings strengthen the idea that aging is not simply the result of general wear and tear on the body. Rather, some scientists suspect that the brain may actively regulate parts of the aging process through inflammation, metabolism, and hormonal signaling.
Can D-serine help humans?
Despite the excitement over this discovery, the research is still in its early stages and was conducted in mice, not humans. Scientists do not yet know whether boosting menin or supplementing with D-serine can safely slow aging or improve cognitive function in humans.
Researchers also warn that altering powerful brain signaling pathways can have unintended consequences. Further research is needed to understand why menin decreases with age, how long the effects last, and whether D-serine supplementation may cause side effects over time.
Still, this study provides an interesting glimpse into how aging may one day be targeted more directly.
Dr. Ren said, “We speculate that the age-related decrease in menin expression in the hypothalamus may be one of the driving factors of aging, and that menin may be an important protein linking genetic, inflammatory, and metabolic factors of aging. D-serine may be a promising therapeutic agent for cognitive decline.”
Leng also pointed out that “Menin signaling in the ventromedial hypothalamus (VMH) is reduced in aged mice, which contributes to the systemic aging phenotype and cognitive impairment. The effects of menin on aging are mediated by neuroinflammatory changes and metabolic pathway signaling with serine deficiency in the VMH, but restoration of menin in the VMH reversed the aging-associated phenotype.”
