What happens to your brain as you age – and what you can do to keep your brain young and healthy
A new study published on March 16th in the open access journal PLOS Biology by Lige Leng and colleagues from Xiamen University in China suggests that a decrease in Menin levels in the hypothalamus could be a significant contributor to aging.
The research reveals a novel driver of physiological aging and proposes that taking a basic amino acid supplement may help reduce some age-related changes.
As the hypothalamus plays a vital role in physiological aging by increasing neuroinflammatory signaling with time, this study highlights the importance of understanding the relationship between inflammation and various age-related processes in both the brain and the body.
A group of researchers led by Lige Leng recently investigated the role of Menin, a protein found in the hypothalamus, in aging. They previously demonstrated that Menin plays a crucial role in inhibiting hypothalamic neuroinflammation, which prompted them to further explore its potential involvement in aging.
Their findings revealed that Menin levels in the hypothalamus, but not in astrocytes or microglia, decline with age. To investigate this phenomenon, they utilized conditional knockout mice in which Menin activity could be suppressed.
Their experiments demonstrated that a reduction of Menin in younger mice resulted in increased hypothalamic neuroinflammation, aging-related traits such as cognitive decline, reductions in bone mass and skin thickness, and slightly reduced lifespan.
The researchers also observed a decrease in the levels of D-serine, an amino acid known for its neurotransmitter function and is occasionally utilized as a dietary supplement, in response to the loss of Menin. D-serine can be found in several food sources, including soybeans, eggs, fish, and nuts. The authors demonstrated that this decline in D-serine was due to the inhibition of an enzyme required for its synthesis, which was regulated by Menin.
Is it possible to alleviate physiological aging signs by reversing the loss of Menin associated with aging?
The researchers conducted an experiment to investigate whether reversing age-related Menin loss could alleviate physiological aging signs. They achieved this by administering the Menin gene into the hypothalamus of older (20-month-old) mice. After 30 days, they observed improved skin thickness and bone mass, enhanced learning, cognition, and balance, which corresponded with increased D-serine levels within the hippocampus, a crucial brain region involved in learning and memory.
Interestingly, comparable cognitive benefits were observed, though not peripheral aging signs, after three weeks of dietary supplementation with D-serine.
There is still much to uncover about the role of Menin in the aging process, such as the underlying mechanisms that lead to its decline and the possibilities of exploiting this pathway. These include the extent to which phenotypic aging can be slowed and the duration for which it can be done, as well as the potential for D-serine supplementation to elicit unknown changes.
Despite this, Lige Leng believes that the reduction of Menin expression in the hypothalamus with age could be “one of the driving factors of aging,” and that Menin could be the “key protein connecting the genetic, inflammatory, and metabolic factors of aging.”
Additionally, D-serine shows promise as a “therapeutic for cognitive decline.”
Leng further notes that a decrease in Menin signaling in the ventromedial hypothalamus (VMH) in aged mice contributes to systemic aging symptoms and cognitive impairment.
“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.”
Source: 10.1371/journal.pbio.3002033
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