Can they do it in humans?

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Can menin help reverse aging processes? Image credit: Juan Moyano/Stocksy.
  • A new study in mice offers for the first time a new factor that drives aging processes.
  • The study authors report that a reduction in menin protein in the brain’s hypothalamus leads to neuroinflammation that can cause hallmarks of aging.
  • The study suggests that supplements of menin and the amino acid D-serine may one day reverse aspects of aging in humans.

A study led by Dr. Lige Leng of Xiamen University in China has identified a previously unknown trigger for aging in mice, and potentially in humans. It involves the age-related reduction of a protein called Menen in the hypothalamus of the brain.

The study reveals that as menin levels decline, the hypothalamus experiences an increase in neuroinflammation that promotes metabolic and cognitive disorders 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 issues can arise.

The study authors also determined that a loss of menin results in reduced levels of an enzyme needed to produce 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, sleep cycle, mood, satiety and libido.

“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, Assistant Professor Richard and Edna Salomon of Molecular Biology, Cellular 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 the part of the brain known as the hypothalamus affects the aging process, including the metabolic and cognitive changes that occur with age. age.”

She noted that “[h]Hypothalamic inflammation is likely to have a general impact on tissue aging and other parts of the brain, such as the hippocampus, which is essential for learning and memory.

The results of the study were supported by several experiments performed on mice.

To assess the effect of menin deficiency, the researchers worked with purpose-bred – or “knockout” – middle-aged mice whose menin levels they could manipulate.

After reducing the mice’s menin levels, the researchers found that the rodents exhibited biomarkers of aging, such as reduced muscle fiber size, skin thickness, bone mass, tail tendon collagen cross-linkingand clock gene expression.

Increased ventricular muscle thickness and DNA methylation levels were also observed. The mice also experienced cognitive decline and their lifespans were slightly shortened.

On the other hand, when researchers supplemented menin levels in 20-month-old mice for 30 days, the mice showed improved learning and memory, bone mass, bone thickness skin and collagen reticulation of 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.

Increased levels of menin in older mice also apparently caused an increase in D-serine in the hippocampus.

“D-serine is important for communication between neurons to maintain optimal brain function as we age,” Dr. Webb explained.

When the researchers directly administered three weeks of D-serine supplements, they found that cognition improved, but not the physiological improvements seen with menin supplementation.

When research involves mice, often its findings do not carry over to humans.

However, Dr. Santosh Kesari, director of neuro-oncology, 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 for the most part a lot of biology is very similar, and I think that’s going to extrapolate to humans.

He suggested that “there are studies that can be conducted to examine hypothalamic, pituitary, adrenal, and other markers of aging, metabolism, and inflammation in the blood of humans.”

“This paper really identifies, I think uniquely, a critical regulation of aging due to this protein called menin, which is expressed in the hypothalamus,” Dr. Kesari said.

“The implication,” according to Dr. Webb, “is that menin activity in a small number of neurons may be a key checkpoint for D-serine levels which, in turn, maintain metabolic health. and cognitive”.

The study authors claim that menin may be the key protein that links genetic, inflammatory and metabolic aging factors.

Dr. Webb noted:

“The menin protein is found in places other than the hypothalamus, including the pituitary and thyroid. This study focuses on menin activity in a small subset of neurons in the hypothalamus. It will be important to know more about whether Menin activity in other places in the body has an impact on aging.

The function of the menine appears to be tissue-specific, acting oppositely in different places. For example, it is considered a tumor suppressor in the lungs, prostate, bones, liver and breast, and at the same time a factor in the development of leukemia.

The precise mechanism by which menin produces neuroinflammation in the hypothalamus is beyond the scope of this study, which also opens up a new and intriguing avenue of research for our understanding of aging.

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