- A new study in mice suggests for the first time a new factor that stimulates aging processes.
- The study’s authors report that a reduction in the protein menin in the brain’s hypothalamus results in neuroinflammation that may trigger hallmarks of aging.
- The study suggests that supplements of menin and the amino acid D-serine may one day be able to reverse aspects of aging in humans.
A study led by Dr. Lige Ling of Xiamen University in China has identified a previously unknown cause of aging in mice and possibly in humans. It involves the age-related reduction of a protein called
The study finds that, as levels of menin decline, the hypothalamus experiences an increase in neuroinflammation that promotes metabolic and cognitive impairments that occur with aging.
The hypothalamus is considered a critically important control center for the body, so when neuroinflammation prevents it from performing its normal function, a wide variety of age-related health problems can develop.
The study’s authors also found that a loss of menin causes a decrease in an enzyme necessary for the production of the neurotransmitter, the amino acid D-serine.
The study is published in PLOS Biology.
The hypothalamus, when healthy, influences the autonomic nervous system and hormones to regulate heart rate, temperature, blood pressure, immune function, hunger and thirst, the sleep cycle, mood, satiety and sex drive.
“The hypothalamus is important to many aspects of healthy aging, including metabolic and cognitive health, the stress response, and the maintenance of circadian rhythms,” explains Dr. Ashley E. Webb, Richard and Edna Salomon, assistant professor of molecular biology, cell biology, out. and biochemistry at Brown University in Providence, RI, who was not involved in the study.
“This study,” said Dr. Webb, “advances our understanding of how the part of the brain known as the hypothalamus influences the aging process, including metabolic and cognitive changes that occur with age.”
She noted that “[h]hypothalamic inflammation likely has a broad influence on aging in tissues and other parts of the brain, such as the hippocampus, which is essential for learning and memory.”
The research findings were supported by several experiments performed on mice.
To assess the effect of menin insufficiency, the researchers worked with specially bred — or “knocked out” — middle-aged mice whose menin levels they could manipulate.
After lowering the mice’s menin levels, the researchers saw that the rodents showed aging biomarkers such as decreased muscle fiber size, skin thickness, bone mass,
Increased ventricular muscle thickness and
On the other hand, when the researchers supplemented menin levels in older 20-month-old mice for 30 days, the mice showed improved learning and memory, bone mass, skin thickness, and cross-linking of collagen in the tail tendon.
These mice also had better levels of inflammation, food intake and metabolic circadian rhythm. They also lived longer than they otherwise would have.
Elevated levels of menin in the older mice apparently also caused an increase in D-serine in the hippocampus.
“D-serine is important for communication between neurons to maintain optimal brain function with age,” explains Dr. Web out.
When the researchers administered D-serine supplements directly for three weeks, they found that cognition improved, but not the physiological improvements seen with menin supplementation.
When research involves mice, the findings often end up not transferring to humans.
Dr. However, Santosh Kesari, director of neuro-oncology, and chair and professor in the Department of Translational Neuroscience at the Pacific Neuroscience Institute, who was not involved in the study, said Medical News Today“I think a lot of biology is very similar for the most part, and I think that will be extrapolated to humans.“
He suggested that “some studies can be done to look at the hypothalamus, pituitary, adrenal gland access and other aging and metabolism and inflammation markers in people’s blood.”
“This paper really, uniquely I think, identifies a critical regulation of aging due to this protein called menin, which is expressed in the hypothalamus,” said Dr. Kesari.
“The implication,” said Dr. Webb, “is that in a small number of neurons, menin activity may be an important checkpoint for D-serine levels that in turn maintain metabolic and cognitive health.”
The study authors argue that menin may be the key protein linking genetic, inflammatory and metabolic factors of aging.
Dr. Webb noted:
“Menin protein is found in other sites besides the hypothalamus, including the pituitary gland and thyroid gland. This study focuses on the activity of menin in a small subset of neurons in the hypothalamus. It will be important to learn more about whether Menin’s activity elsewhere in the body influences aging.”
The function of menin seems to be
The precise mechanism by which menin causes neuroinflammation in the hypothalamus is beyond the scope of this study, which otherwise opens up a new and intriguing avenue of research for our understanding of aging.