Scientists develop a new answer to the question of how to measure aging – with interesting results.

In a new study using a new analytical approach to make influences on aging processes measurable, researchers have taken a close look at three treatment approaches that have been widely believed to slow the aging process. However, when tested in mice, these treatments proved largely ineffective in their supposed impact on aging.

Longevity.Technology: Aging is a complex and multifaceted process that is influenced by a variety of genetic, environmental and lifestyle factors. The upshot is that it is difficult to measure aging in a standardised and objective way. Add into the mix the challenges that aging manifests differently in different individuals, the rate at which it occurs can vary widely and the fact that aging is a dynamic process that occurs over a long period of time, and measuring aging almost seems impossible using traditional experimental methods.

Furthermore, there are many different aspects of aging, such as physical, cognitive and social changes, that can be difficult to quantify and compare. Measuring overall aging requires the use of complex and multidimensional approaches that take into account these various factors and the complex interplay between them, so it is no surprise that for this latest study, researchers went back to the drawing board. What they found, however, is more than a little surprising…

“There is no internal clock of aging that you can regulate with a simple switch – at least not in the form of the treatments studied here,” said Dr Dan Ehninger of the DZNE, the initiator of the study, explaining the team’s new analytical approach to make influences on aging processes measurable [1].

The study, the results of which have now been published in the journal Nature Communications, involved researchers from DZNE, Helmholtz Munich and the German Center for Diabetes (DZD).

“We chose three regulators for our interventions that many experts believe slow down aging,” explains Professor Martin Hrabě de Angelis, head of the Institute of Experimental Genetics and director of the German Mouse Clinic at Helmholtz Munich, who also drove the project with his team [1].

One target is intermittent fasting, in which the calories consumed are reduced. The second targets a central node of cell metabolism (mTOR), which is also the target of the supposed antiaging drug rapamycin. And the third interferes with the release of growth hormone [2]. Similar treatments are also used by humans, although their efficacy with regard to aging has not been sufficiently proven.

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 Ehninger, who is a senior scientist at DZNE [1].

A key question is 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, giving the example that up to 90 percent of mice die from tumours 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 find many genes that suppress tumor development – and not necessarily genes that play a general role in aging [1].”

This meant that for their study, the scientists decided on an approach that does not emphasise lifespan per se, 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 Hrabě de Angelis. “The health check results in a compendium of hundreds of factors covering many areas of physiology.”

This means generating an exact description of the state of the animal at the moment of examination – and this was 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, the animals and approaches were analyzed and compared; the team considered how much does each parameter typically change at a given stage of life and whether 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, say the researchers. Although the team was able to identify individual cases in which old mice looked younger than they actually were, it was clear to them that this was not down to treatment.

“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 [1].”

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 and they hope this new research method will provide a more comprehensive picture of possible treatment approaches and their effectiveness.

[1] https://www.dzne.de/en/news/press-releases/press/longevity-treatments-do-not-slow-aging/
[2] https://www.nature.com/articles/s41467-022-34515-y