LifeLongFit project receives funding to explore the effects of mild stress on healthy aging

Dr. Maria Ermolaeva from the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena has received the coveted ERC Consolidator Grant from the EU, in the sum of two million euros. The LifeLongFit project, now funded for the next five years, is looking at ways to contribute to healthier aging through the influence of mild stress.

Staying fit for life! Who doesn't dream of this when the first signs of aging start to appear in middle age, when our muscles ache, our hair turns grayer, and a bit of physical activity leaves us out of breath. However, aging is a very complex, multi-layered process that is influenced by a variety of internal and external factors. What is urgently needed is a fundamental understanding of the aging process and the emergence of aging-associated diseases, in order to be able to develop solutions for healthy aging.

Dr. Maria Ermolaeva, leader of the Research Group "Stress Tolerance and Homeostasis" at the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena, has received the coveted ERC Consolidator Grant from the EU, with two million euros in funding for the LifeLongFit project, which will spend the next five years looking for ways to improve health as we age. The funding will create up to four new positions at the FLI.

What happens as we age?

As we grow older, more and more damage accumulates in our body, which in turn triggers other forms of harm: for example, our genetic material can become damaged and communication between cells can be disrupted, or the misfolding and clumping of proteins can occur. "These are all things that are harmful to the organism and can lead to disease," reports Dr. Ermolaeva, "but if we are still young and fit, then our body is able to efficiently mitigate such damage through its own repair mechanisms, so that our health is not affected. However, as we grow older, these specialized mechanisms lose their effectiveness and become error-prone leading to dramatic consequences for our bodies."

Effects of moderate stress on aging

Maintaining the body's own damage mitigation mechanisms is therefore one way to age healthily. This can be achieved through moderate stress, which sets off a targeted stress response and thus stimulates repair processes. "Mild stressors have the effect of triggering repair pathways that contribute to the elimination of damaged or no longer functional cellular components, which effectively leads to preservation of cellular functions for longer time," adds Dr. Ermolaeva.

Dr. Ermolaeva's research group has already been able to demonstrate in studies on the nematode worm C. elegans that mild stressors – such as the administration of the antidiabetic drug metformin, exposure to mildly pathogenic microbes, or UV radiation – caused the animals to become healthier than the control group without stress. In addition, the moderately stressed worms were more robust and subsequently less susceptible to further stressors.

Different effects on young and old

When treating young and old nematodes with metformin, the FLI researchers unexpectedly ran into a serious problem. "The knowledge and assumptions of how older animals will react to stress is based on experimental data obtained mostly in young animals," explains Dr. Ermolaeva, "but this turned out to be a major issue, especially in this experiment." While positive effects were visible in young worms, the drug lost its effect in older specimens and was even toxic to them. "This means that it cannot be assumed from the outset that the results can be transferred one-to-one from young to old, but shows once again how important it is to study the effect of moderate stress in an age-specific manner by also taking into account changes in metabolism or repair activities," emphasizes the biochemist.

Timing of dosage influences rejuvenation effect

This led to the idea of the LifeLongFit project, an exceptionally time-consuming and risky research approach. The project aims to investigate the influence of a variety of potential mild stressors (e.g., food restriction, microbes, and UV radiation) at different age to determine whether their positive effects are reversed during aging similar to those of metformin. Subsequently, ways of re-activating positive stress responses late in life will be screened for.

This knowledge is essential for deriving an individualized, appropriate treatment for an individual according to age. Ultimately, the main goal of the project is to suggest new pathways for healthy aging that do not require early or even lifelong treatment with drugs, but can be started at any point in life, including old age. "I am very pleased about the ERC grant, and I am very proud and happy to be able to come closer to this challenging goal with my team and the support of the FLI," reports Dr. Ermolaeva.

"The LifeLongFit project does involve high risks and requires extensive resources," adds Prof. Alfred Nordheim, Scientific Director of the FLI, "but if the project is successful, it offers enormous opportunities to use this knowledge to develop novel therapies that promote healthy aging. We wish Dr. Ermolaeva and her team the best of luck in this endeavor!"