The NIA’s intervention testing program, which included UT Health San Antonio, worked with counterparts in Switzerland and Tennessee.
The intervention trial program, which is funded by the National Institute on Aging (NIA), has reported the discovery of many candidate genes that influence longevity. All three intervention trial program sites — the University of Texas Health Science Center in San Antonio, the University of Michigan in Ann Arbor, and the Jackson Laboratory in Bar Harbor, Maine — collaborated with Johan Auwerx’s lab at the École Polytechnique Fédérale de Lausanne in Lausanne, Switzerland, and the laboratory of Robert W. Williams at the University of Tennessee Health Sciences Center in Memphis.
“Some candidate genes impacted female lifespan while others affected male lifespan,” said Randy Strong, PhD, of the Sam and Ann Barshop Institute for Longevity and Aging Studies at UT. Health San Antonio. “A group of genes increased the longevity of both sexes. In a rarity for these types of studies, the findings were made in a mouse population with genetic diversity comparable to human populations.
The results were recently published in the prestigious journal Science. Strong is the Site Director of the Barshop Institute Intervention Testing Program, which received its first National Institute on Aging (NIA) grant for the program in 2003 and is now in its 19th year of NIA support.
“The study models what happens in people,” said research co-author James Nelson, Ph.D., of the Barshop Institute. “Unlike the mice in many other studies, the mice in this recently 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 have a impact on aging.
As we age, even small differences can have a significant impact on our health. The hemoglobin protein in red blood cells, for example, can become less efficient at binding oxygen and transporting it from the lungs to body tissues due to slight variations in the hemoglobin gene, according to Nelson. One result is anemia.
Finding genetic loci that influence longevity only in females is interesting and important, Strong said. Genetic loci are groups of 10 to 100 genes.
“Women and men differ in almost every aspect of aging that you can explore,” Strong said. “They each need to be studied, both to understand the aging of both sexes and to develop effective treatments. If we offer the same drug therapies to women that we offer to men, and women’s aging is caused by different genes, we are not going to be as effective in our treatments.
Confirmation in roundworms
The next steps are to examine these candidate genes to find those responsible for increased longevity. In the final part of the Science article, the team reported doing just that. The researchers tested candidate genes in roundworms, which are often used in aging research due to their short lifespan. “A number of candidate genes affected worm longevity,” Nelson said.
This does not prove that these same genes in humans will affect human lifespan, the researchers said. But it’s another reason to continue to study the genetic basis of longevity.
Powerful study design
As expected when the intervention testing program began, having three sites where studies are conducted ensures statistical power, rigor and reproducibility of results, Strong said.
The study is unique in that it is based on a large sample of animals numbering several thousand, the authors said. “This is one of the largest numbers of mice in any study that has attempted to identify genes that influence lifespan,” Nelson said.
Reference: “Genetics of sex- and age-dependent longevity in a heterogeneous population of mice” by Maroun Bou Sleiman, Suheeta Roy, Arwen W. Gao, Marie C. Sadler, Giacomo VG von Alvensleben, Hao Li, Saunak Sen , David E. Harrison, James F. Nelson, Randy Strong, Richard A. Miller, Zoltán Kutalik, Robert W. Williams and Johan Auwerx, September 30, 2022, Science.
The study was funded by the National Institute on Aging.
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