Researchers led by Dr. Lige Leng at Xiamen University in China have discovered a new trigger for aging in mice, which may also apply to humans.
The reduction of a protein called menin in the hypothalamus of the brain as we age is linked to an increase in neuroinflammation, which causes metabolic and cognitive disorders.
The hypothalamus is an important control center for the body, regulating many functions such as heart rate, temperature, immune function, and mood. The reduction in menin levels also causes a decrease in the production of the neurotransmitter D-serine.
The study highlights the importance of the hypothalamus in healthy aging and its impact on other parts of the brain, such as the hippocampus, which is important for learning and memory.
The findings are published in PLOS Biology.
Several experiments performed on mice supported the study’s findings. The researchers manipulated menin levels in middle-aged “knockout” mice to assess the effect of menin insufficiency.
After reducing the mice’s menin levels, the researchers observed several aging biomarkers, such as reduced muscle fiber size, skin thickness, bone mass, tail tendon collagen cross-linking, clock gene expression, increased ventricular muscle thickness, and DNA methylation levels.
These mice also experienced cognitive decline, slightly shortened lifespan, and were supplemented with menin levels for 30 days. The mice then exhibited improved learning and memory, bone mass, skin thickness, tail tendon collagen cross-linking, inflammation levels, food intake, and metabolic circadian rhythm, and lived longer than they would have otherwise.
Increasing menin levels in the older mice also increased D-serine in the hippocampus, which is essential for communication between neurons to maintain optimal brain function with age. When the researchers administered three weeks of D-serine supplements directly, they found that cognition improved, but not the physiological improvements seen with menin supplementation.
According to Dr. Santosh Kesari, who is the director of Neuro-oncology and a professor at the Pacific Neuroscience Institute, the biology of mice and humans is mostly similar, and he thinks the findings of the study could apply to humans.
He suggested that future studies could examine the hypothalamic-pituitary-adrenal axis and other markers of aging, metabolism, and inflammation in humans’ blood.
Dr. Kesari, who was not involved in the study, stated that the study “uniquely identifies a critical regulation of aging due to this protein called menin, which is expressed in the hypothalamus.” This implies that menin activity in a small number of neurons may play a key role in maintaining metabolic and cognitive health through the regulation of D-serine levels. The study’s authors suggest that menin may be the critical protein that links genetic, inflammatory, and metabolic aging factors.
Dr. Webb, also not involved in the study, explained that menin protein is found in other areas besides the hypothalamus, including the pituitary and thyroid glands. While this study concentrates on menin’s activity in a small group of hypothalamic neurons, it will be crucial to investigate whether menin’s activity in other parts of the body affects aging. Menin’s function seems to be tissue-specific, acting in opposite ways in different places. For example, it is considered a tumor suppressor in some areas and a factor in the development of leukemia in others.
While the precise mechanism by which menin produces neuroinflammation in the hypothalamus remains unclear, this study offers a new and interesting research avenue for our understanding of aging.