Science identifies key protein that could be used to extend healthy human lifespan

Decades of research have shown that limiting caloric intake in fruit flies, worms and mice can extend lifespan under laboratory conditions

The findings were published in the journal Science on February 10, 2022

The study is based on findings from the Comprehensive Evaluation of the Long-Term Effects of Reduced Energy Intake (CALERIE) clinical trial, the first controlled study of calorie restriction in healthy individuals

Vishwa Deep Dixit, Waldemar Von Zedtwitz Professor of Pathology, Immunobiology and Comparative Medicine and senior author of the study, said the overall goal of this clinical trial is to see if caloric restriction works as well in humans as it does in laboratory animals beneficial

Since previous studies have shown that restricting caloric intake in mice increases infection, Deep Dixit also wanted to determine the relationship between caloric restriction and inflammation and immune responses

"Because we know that chronic, low-grade inflammation in humans is a major contributor to many chronic diseases and therefore has a negative impact on lifespan," said Deep Dixit, director of the Yale Center for Aging Research

Deep Dixit and his team started by analyzing the thymus

In this study, the research team used magnetic resonance imaging (MRI) to determine whether there were functional differences in the thymus glands of people with and without calorie restriction

Deep Dixit said: "The fact that this organ can be rejuvenated is shocking to me because there is very little evidence that this happens in humans

With the effects on the thymus so pronounced, Deep Dixit and his colleagues hope to also find effects on immune cells produced by the thymus, changes that may underlie the overall benefits of calorie restriction

This observation, which required a closer look by the researchers, revealed a surprising finding: "It turns out that the effect is actually in the tissue microenvironment, not in blood T cells," Deep Dixit said

Deep Dixit and his team studied adipose tissue, or body fat, in participants undergoing calorie restriction at three time points: at the start of the study, one year later, and two years later

Deep Dixit said: "We found significant changes in gene expression in adipose tissue after one year that persisted into the second year

Recognizing this, the researchers set out to investigate whether the genes they identified in their analysis might drive some of the beneficial effects of calorie restriction

Changes in PLA2G7 gene expression were observed in calorie-restricted participants, suggesting that this protein may be involved in the effects of calorie restriction

Olga Spadaro, a former research scientist at the Yale School of Medicine and lead author of the study, said: "We found that the benefits of reducing PLA2G7 in mice were significantly correlated with the The benefits from calorie restriction that we see in humans are similar

These effects occur because PLA2G7 targets a specific inflammatory mechanism called the NLRP3 inflammasome, the researchers said
.
Reducing PLA2G7 protects aged mice from inflammation
.

"These findings suggest that PLA2G7 is one of the drivers of the effects of calorie restriction," said Deep Dixit.
"
Identifying these drivers helps us understand how the metabolic and immune systems communicate with each other, which could point us toward improving immune function, reducing Inflammation, and possibly even a potential target for extending healthy lifespan
.
"

For example, manipulating PLA2G7 has the potential to gain the benefits of calorie restriction without actually restricting calories, which could be detrimental for some people, he said
.

Deep Dixit said: “There is a lot of debate about which diet is better, low carb or fat, increased protein, intermittent fasting, etc.
I think time will tell which diets are more important
.
But CALERIE is a very strict Controlled studies, which show that simply cutting calories, rather than a specific diet, has a dramatic effect on biology and shifts the immune-metabolic state in a direction that protects human health
.
So from a public health standpoint, I think this gave us hope
.
"

Reference: "Caloric restriction has a new player" by Timothy W.
Rhoads and Rozalyn M.
Anderson, 10 February 2022, Science .

DOI: 10.
1126/science.
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