Tissue Regeneration and Aging

Regenerative capacity of organs and tissues decreases with age and first signs of diminished resilience of elderly as compared to young individuals are observed as early as at the age of 45 to 50 after traumatic injuries. Besides several other factors, cellular senescence has been identified as a key driver of aging, age-associated diseases and thus also of diminished resilience. Indeed, eliminating senescent cells in various pre-clinical models of age-associated diseases including osteoarthritis or osteoporosis, but also in cartilage or bone regeneration after traumatic injuries leads to later onset or improvement of the specific conditions.

In order to understand how senescent cells that accumulate within organisms with age negatively impact on organ and tissue function and regeneration, we focus on function of miRNAs (Brenner et al., 2021; Terlecki-Zaniewicz et al., 2019) and proteins differentially regulated in senescent and stressed cells, in tissue culture models (Weinmuellner et al., 2017; Weinmüllner et al., 2020) and their impact on tissue regeneration and organismal aging (Heissenberger et al., 2020, 2019; Schosserer et al., 2015), which also allows for identifying novel senolytic targets and therapeutics. In addition, the pro-inflammatory activity of senescent cells via its senescence associated secretory phenotype (SASP) is considered a prominent driver of the aging process and inhibitor of sufficiently boosting pro-regenerative activity of the endogenous repair mechanisms. Therefore, we focus on SASP factors including lipids (Narzt et al., 2020; Pils et al., 2021) and circulating miRNAs as biomarkers for senescent cell loads in organisms or as diagnostics in age-associated diseases as well as on the pro-inflammatory SASP (Grillari et al., 2020; Hackl et al., 2015; Heilmeier et al., 2022; Morsiani et al., 2021) as a therapeutic target. We are specifically interested in developing extracellular vesicles of MSCs into potential therapeutic strategies for tissue regeneration in young and elderly individuals as a platform technology (Gimona et al., 2021; Vogt et al., 2021, 2018) that will be tested in cooperation with all groups of LBI Trauma, especially in the context of wound healing, as well as in bone, cartilage and neuroregeneration.