Researchers tested common treatments for aging, including intermittent fasting, which reduces calorie expenditure, targeting the central node of cellular metabolism (mTOR), and interfering with the release of growth hormone.
A new study explores the effectiveness of three therapeutic approaches previously thought to slow the aging process. However, when tested in mice, researchers found that these treatments had limited effects on aging.
“There is no biological clock for aging that can be regulated by a simple switch, at least not in the form of therapy being studied here,” concludes Dan Enninger, Ph.D., of DZNE, who initiated the study. The team has developed a new analytical approach that makes it possible to measure the effects on the aging process.
The study, conducted by researchers from the DZNE, Helmholtz Munich, and the German Diabetes Center (DZD), was published in the journal.
For the assessment in mice, the scientists developed a new answer to the question of how to measure aging. “Many researchers in recent decades have used lifespan as an indirect measure of aging,” explains Dan Ehninger, who is a senior scientist at DZNE. So, for example, how old do mice get — and how can that lifespan be extended?
“It is often assumed that if they just live longer, they will also age more slowly. But the problem is that mice, like many other organisms, do not die from general old age, but from very specific diseases,” says Ehninger. For example, up to 90 percent of mice die from tumors that form in their bodies at an advanced age.
“So, if you were to look at the whole genome for factors that make mice become long-lived, you would like to find many genes that suppress tumor development — and not necessarily genes that play a general role in aging.”
For their study, the scientists, therefore, chose an approach that does not emphasize lifespan but rather focused on a comprehensive investigation of age-related changes in a wide range of bodily functions.
“You can think of it as a complete health status survey,” says Martin Hrabě de Angelis: “The health check results in a compendium of hundreds of factors covering many areas of physiology” — an exact description of the state of the animal at the moment of examination.
That’s exactly the approach the researchers applied to the animals subjected to one of the three treatment approaches that supposedly slow aging. Across different life stages, they were analyzed and compared: How much does each parameter typically change at a given stage of life? And, do parameters change more slowly when the mice are given one of the three treatments? This study design makes it possible to determine precisely whether the natural aging process can be slowed and with it the deterioration of important physiological functions.
The results were unambiguous: Although the researchers were able to identify individual cases in which old mice looked younger than they actually were it was clear that “this effect was not due to slowing down aging, but rather due to age-independent factors,” says Dan Ehninger. “The fact that a treatment already has its effect in young mice – prior to the appearance of age-dependent change in health measures – proves that these are compensatory, general health-promoting effects, not a targeting of aging mechanisms.”
The DZNE and Helmholtz Diabetes Center teams have now set their sights on the next goal: They want to investigate other treatment approaches that experts believe can slow aging. The researchers hope that the new research method will provide a more comprehensive picture of possible treatment approaches and their effectiveness.
Reference: “Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice” by Kan Xie, Helmut Fuchs, Enzo Scifo, Dan Liu, Ahmad Aziz, Juan Antonio Aguilar-Pimentel, Oana Veronica Amarie, Lore Becker, Patricia da Silva-Buttkus, Julia Calzada-Wack, Yi-Li Cho, Yushuang Deng, A. Cole Edwards, Lillian Garrett, Christina Georgopoulou, Raffaele Gerlini, Sabine M. Hölter, Tanja Klein-Rodewald, Michael Kramer, Stefanie Leuchtenberger, Dimitra Lountzi, Phillip Mayer-Kuckuk, Lena L. Nover, Manuela A. Oestereicher, Clemens Overkott, Brandon L. Pearson, Birgit Rathkolb, Jan Rozman, Jenny Russ, Kristina Schaaf, Nadine Spielmann, Adrián Sanz-Moreno, Claudia Stoeger, Irina Treise, Daniele Bano, Dirk H. Busch, Jochen Graw, Martin Klingenspor, Thomas Klopstock, Beverly A. Mock, Paolo Salomoni, Carsten Schmidt-Weber, Marco Weiergräber, Eckhard Wolf, Wolfgang Wurst, Valérie Gailus-Durner, Monique M. B. Breteler, Martin Hrabě de Angelis and Dan Ehninger, 11 November 2022, Nature Communications.
DOI: 10.1038/s41467-022-34515-y
