Could more of the protein Menin reverse aging? New study revives youth

Aging may be significantly influenced by the reduction of a protein called menin, found in the hypothalamus, according to a new study.

The research identifies a previously unidentified mechanism that accelerates physiological aging and raises the possibility that supplementing with a basic amino acid could reverse some of the effects of aging.

How does the protein menin impact aging?

Lige Leng of Xiamen University in Xiamen, China, and colleagues wanted to investigate the possible role of menin in aging after discovering that it is an essential inhibitor of hypothalamic neuroinflammation. 

Initially, they found that aging causes a drop in menin levels in the hypothalamus but not in astrocytes or microglia.

To further study this decline, they created conditional knockout mice that allowed for the regulation of menin activity. It was discovered that lower levels of menin in young mice resulted in an increase in hypothalamic neuroinflammation and aging-related traits.

This included decreased bone density, skin thickness, cognitive decline, and a significantly shorter lifespan.

Additionally, the team discovered that another decrease brought on by a decline in menin was the amino acid and neurotransmitter D-serine, which is present in foods like soybeans, eggs, fish, and nuts.

They demonstrated that the cause of this drop was due to a decrease in activity from an enzyme involved in its synthesis (which was, in turn, regulated by Menin).

How can aging be reversed?

The next step was for the researchers to determine whether stopping the age-related Menin loss also prevented the physiological effects of aging. They did this by implanting the Menin gene into the hypothalamus of 20-month-old mice.

Remarkably, 30 days later, they discovered enhanced skin thickness, bone mass, learning, cognition, and balance, which were all associated with an increase in D-serine in the hippocampus- a part of the brain crucial for memory and learning.

Better yet, three weeks of dietary supplementation with D-serine could result in similar advantages on cognition, though not on the peripheral symptoms of aging.

"We speculate that the decline of Menin expression in the hypothalamus with age may be one of the driving factors of aging," said Leng in a press release. 

"Menin may be the key protein connecting the genetic, inflammatory, and metabolic factors of aging. D-serine is a potentially promising therapeutic for cognitive decline."

The researchers highlighted that there is still much to learn about the role of Menin in aging, including the upstream mechanisms that cause its decline. Further research is needed to assess the potential for utilizing this newly identified pathway, including how much and how long phenotypic aging can be slowed. 

Also yet to be identified is whether supplementing with D-serine may cause other unanticipated changes. 

The full study was published in PLOS Biology on March 16 and can be found here.