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Xie, Kan; Fuchs, Helmut; Scifo, Enzo; Liu, Dan; Aziz, Ahmad; Aguilar-Pimentel, Juan Antonio; Amarie, Oana Veronica; Becker, Lore; da Silva-Buttkus, Patricia; Calzada-Wack, Julia; Cho, Yi-Li; Deng, Yushuang; Edwards, A. Cole; Garrett, Lillian; Georgopoulou, Christina; Gerlini, Raffaele; Hoelter, Sabine M.; Klein-Rodewald, Tanja; Kramer, Michael; Leuchtenberger, Stefanie; Lountzi, Dimitra; Mayer-Kuckuk, Phillip; Nover, Lena L.; Oestereicher, Manuela A.; Overkott, Clemens; Pearson, Brandon L.; Rathkolb, Birgit; Rozman, Jan; Russ, Jenny; Schaaf, Kristina; Spielmann, Nadine; Sanz-Moreno, Adrian; Stoeger, Claudia; Treise, Irina; Bano, Daniele; Busch, Dirk H.; Graw, Jochen; Klingenspor, Martin; Klopstock, Thomas; Mock, Beverly A.; Salomoni, Paolo; Schmidt-Weber, Carsten; Weiergraber, Marco; Wolf, Eckhard; Wurst, Wolfgang; Gailus-Durner, Valerie; Breteler, Monique M. B.; Hrabe de Angelis, Martin and Ehninger, Dan (2022): Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice. In: Nature Communications, Vol. 13, No. 1, 6830

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Abstract

Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice. For each phenotype, we establish lifetime profiles to determine when age-dependent change is first detectable relative to the young adult baseline. We examine key lifespan regulators (putative anti-aging interventions;PAAIs) for a possible countering of aging. Importantly, unlike most previous studies, we include in our study design young treated groups of animals, subjected to PAAIs prior to the onset of detectable age-dependent phenotypic change. Many PAAI effects influence phenotypes long before the onset of detectable age-dependent change, but, importantly, do not alter the rate of phenotypic change. Hence, these PAAIs have limited effects on aging. Lifespan can be affected by both physiological ageing and specific sets of pathologies associated with old age. Here the authors report a resource of large-scale cross-sectional phenotyping of aging male mice at different time points to analyse a large set of phenotypes and molecular markers, including during genetic and diet interventions affecting lifespan.

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