- A new study in mice suggests for the first time a new factor that controls aging processes.
- The authors of the study report that a decrease in the protein menin in the brain’s hypothalamus leads to neuroinflammation, which can cause signs of aging.
- Research suggests that supplements of menin and the amino acid D-serine may one day be able to reverse aspects of aging in humans.
Research led by Dr. Lige Leng of Xiamen University in China has identified a previously unknown trigger of aging in mice and possibly humans. It is accompanied by an age-related decrease in the protein
The study states that when menin levels decrease, neuroinflammation in the hypothalamus increases, which contributes to the metabolic and cognitive disorders that occur with aging.
The hypothalamus is considered a critically important control center of the body, so when inflammation of the nervous system prevents it from performing its normal functions, a variety of age-related health problems can occur.
The study authors also noted that loss of menin reduces levels of an enzyme needed to produce the neurotransmitter, the amino acid D-serine.
The study was 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, sleep cycle, mood, satiety, and sex drive.
“The hypothalamus is important for many aspects of healthy aging, including metabolic and cognitive health, stress response, and maintenance of circadian rhythms,” explained Dr. Ashley E. Webb, Richard and Edna Salomon Associate Professor of Molecular Biology, Cell Biology. and biochemistry at Brown University in Providence, RI, who was not involved in the study.
“This study,” Dr. Webb said, “advances our understanding of how a part of the brain known as the hypothalamus affects the aging process, including the metabolic and cognitive changes that occur with age.”
He noted that “[h]inflammation of the hypothalamus is likely to have widespread effects on aging tissues and other parts of the brain, such as the hippocampus, which is essential for learning and memory.
The research results were supported by several experiments on mice.
To assess the effect of menin deficiency, the researchers worked with middle-aged purpose-bred, or “outbred” mice, whose menin levels they could manipulate.
After reducing the level of the meninges in the mice, the researchers found that the rodents showed aging biomarkers such as reduced muscle fiber size, skin thickness, bone mass,
Increased ventricular muscle thickness and
On the other hand, when researchers supplemented the menin levels of aged 20-month-old mice for 30 days, the mice had improved learning and memory, bone mass, skin thickness, and tail tendon collagen cross-linking.
These mice also had better levels of inflammation, food intake and metabolic circadian rhythm. They also lived longer than usual.
Increased menin levels in older mice also apparently resulted in increased D-serine in the hippocampus.
“D-serine is important for communication between neurons to maintain optimal brain function as we age,” explained Dr. Webb.
When the researchers administered three weeks of D-serine supplements directly, they found that cognition improved, although not the physiological improvements seen with menin supplementation.
When research involves mice, its findings often do not transfer to humans.
However, Dr. Santosh Kesari, director of neuro-oncology and chair and professor of translational neuroscience at the Pacific Neuroscience Institute, who was not involved in the study, said. Medical news today: “I think most of biology is very similar, and I think this extrapolates to humans.“
He suggested that “some studies can be done to look at hypothalamic, pituitary, adrenal access and other markers of aging and metabolism and inflammation in human blood.”
“This paper really identifies, in what I think is a unique way, a critical regulation of aging that is caused by this protein called menin that is expressed in the hypothalamus,” said Dr. Kesari.
“The implication,” according to Dr. Webb, “is that menin activity in a small number of neurons may be a key control point for D-serine levels, which in turn maintains metabolic and cognitive health.”
The authors of the study argue that menin may be a key protein that links genetic, inflammatory and metabolic factors of aging.
Dr. Webb noted:
“Menin protein is found elsewhere in the hypothalamus, including in the pituitary gland and thyroid gland. This study focuses on the function of menin in a small subset of neurons in the hypothalamus. It is important to learn more about whether menin function elsewhere in the body affects aging.
Menin’s mission seems to be
The exact mechanism by which menin produces neuroinflammation in the hypothalamus is beyond the scope of this study, which otherwise opens up a new and fascinating avenue of research for understanding aging.