Prolonged longevity in mice with gene clusters

Numerous candidate genes that affect longevity have recently been found, according to research from the Interventions Testing Program, which is supported by the National Institute on Aging (NIA).

The University of Tennessee Health Science Center at Memphis and Johan Auwerx, MD, PhD, of the École Polytechnique Fédérale de Lausanne in Lausanne, Switzerland worked together on the study with the three Interventions Testing Program sites: The University of Texas Health Science Center at San Antonio, The University of Michigan at Ann Arbor, and The Jackson Laboratory at Bar Harbor, Maine.

Some candidate genes impacted female life span while others affected the male life span. One cluster of genes increased longevity of both sexes. In a rarity for these types of studies, the findings were made in a population of mice with genetic diversity comparable to human populations.”

Randy Strong, Professor, Sam and Ann Barshop Institute for Longevity and Aging Studies, UT Health San Antonio

The findings were released on September 30^th, 2022, in the prestigious journal Science. Strong is the director of the Barshop Institute’s Interventions Testing Program, which received its initial National Institute on Aging (NIA) grant funding program in 2003 and is now in its 19^th year of NIA support.

Genetic smorgasbord

The study models what happens in people. Unlike mice in many other studies, mice in this newly reported research are not all the same. Each has different genetic variants, resulting in slightly different proteins that do slightly different things, which together can impact aging.”

James Nelson, Study Co-Author and Professor, Cellular and Integrative Physiology, Barshop Institute, UT Health San Antonio

As people age, even minute variations can have a significant impact on health. The hemoglobin protein in red blood cells, for instance, could become less efficient at adhering to oxygen and carrying it from the lungs to the body’s tissues as a result of minor mutations in the hemoglobin gene, according to Nelson. One consequence is anemia.

Female longevity

Strong cited the identification of genetic loci that only affect female longevity as being interesting and significant. Genetic loci are clusters of 10–100 genes.

Strong added, “Females and males differ in almost every aspect of aging you can explore. They each must be studied, both to understand aging in the two sexes and to develop effective treatments. If we offer the same drug therapies to females that we offer to males, and females’ aging is caused by different genes, we are not going to be as effective in our treatments.”

Confirmation in roundworms

The next step is to carefully examine these potential genes to identify those that contribute to enhanced longevity. The researchers described achieving this in the latter section of the study. Roundworms, which are usually utilized in aging studies due to their brief lifespan, were utilized by researchers to examine potential genes.

“A number of the candidate genes did affect longevity in the worms,” Nelson added.

According to the researchers, this does not establish that the same genes in people will have an impact on life expectancy. But it is yet another argument in favor of keeping up research on the genetics of lifespan.

Powerful study design

Strong added that having three study locations provides statistical power, rigor, and reproducibility of results, as was intended when the Interventions Testing Program was first established.

According to the authors, the study is distinctive because it is centered on a substantial animal sample, numbering in the thousands.

Nelson stated, “It is among the largest number of mice of any study that has attempted to identify genes that influence life span.”