During the aging process, different stress response pathways, such as the unfolded protein response (UPR), the mitochondrial stress response (MSR), and the DDR – as studied in RA-1 – are tightly coordinated, thereby ensuring physiological integrity especially upon metabolic changes. Notably, different tissues have differing metabolic profiles that confer different responses when disturbances of these pathways occur. Beyond the cell autonomous control of these critical aging-regulating pathways, recent studies have identified cell non-autonomous regulation of cellular stress responses, suggesting interorgan communication mechanisms that are intricately balanced for integration and maintenance of the entire organism. Moreover, most studies to date have mainly addressed individual stress response pathways rather than examined their systemic coordination in specific cell types or between different organs. Thus, RA-2 aims to unravel the interplay between homeostasis pathways at the molecular, cellular, and organismal level as well as to define adaptation mechanisms in response to aging or inherited, disease-associated mutations. The key objectives of RA-2 are to investigate:

1. metabolic and stress signaling in the epidermal communication axis,
2. metabolic and stress signaling in the gut epithelium,
3. metabolic and age-related adaptation of skeletal muscle,
4. age-related multimorbidity of chronic kidney disease,
5. interorgan and cell non-autonomous communication from an organismal perspective,
6. germ cell-induced systemic stress response pathways.