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Xie, K.* ; Fuchs, H. ; Scifo, E.* ; Liu, D.* ; Aziz, A.* ; Aguilar-Pimentel, J.A. ; Amarie, O.V. ; Becker, L. ; da Silva Buttkus, P. ; Calzada-Wack, J. ; Cho, Y.-L. ; Deng, Y.* ; Edwards, A.C.* ; Garrett, L. ; Georgopoulou, C.* ; Gerlini, R. ; Hölter, S.M. ; Klein-Rodewald, T. ; Kramer, M.* ; Leuchtenberger, S. ; Lountzi, D.* ; Mayer-Kuckuk, P. ; Nover, L.L.* ; Oestereicher, M.A. ; Overkott, C.* ; Pearson, B.L.* ; Rathkolb, B. ; Rozman, J. ; Russ, J.* ; Schaaf, K.* ; Spielmann, N. ; Sanz-Moreno, A. ; Stoeger, C. ; Treise, I. ; Bano, D.* ; Busch, D.H.* ; Graw, J. ; Klingenspor, M.* ; Klopstock, T.* ; Mock, B.A.* ; Salomoni, P.* ; Schmidt-Weber, C.B. ; Weiergräber, M.* ; Wolf, E.* ; Wurst, W. ; Gailus-Durner, V. ; Breteler, M.M.B.* ; Hrabě de Angelis, M. ; Ehninger, D.*

Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice.

Nat. Commun. 13:6830 (2022)

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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.

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