Collinge Charles W, Razzoli Maria, Mansk Rachel, McGonigle Seth, Lamming Dudley W, Pacak Christina A, van der Pluijm Ingrid, Niedernhofer Laura, Bartolomucci Alessandro
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA.
Department of Medicine, University of Wisconsin, Madison, WI, USA.
Geroscience. 2025 Feb;47(1):85-107. doi: 10.1007/s11357-024-01263-4. Epub 2024 Jul 11.
Various approaches exist to quantify the aging process and estimate biological age on an individual level. Frailty indices based on an age-related accumulation of physical deficits have been developed for human use and translated into mouse models. However, declines observed in aging are not limited to physical functioning but also involve social capabilities. The concept of "social frailty" has been recently introduced into human literature, but no index of social frailty exists for laboratory mice yet. To fill this gap, we developed a mouse Social Frailty Index (mSFI) consisting of seven distinct assays designed to quantify social functioning which is relatively simple to execute and is minimally invasive. Application of the mSFI in group-housed male C57BL/6 mice demonstrated a progressively elevated levels of social frailty through the lifespan. Conversely, group-housed females C57BL/6 mice manifested social frailty only at a very old age. Female mice also showed significantly lower mSFI score from 10 months of age onward when compared to males. We also applied the mSFI in male C57BL/6 mice under chronic subordination stress and in chronic isolation, both of which induced larger increases in social frailty compared to age-matched group-housed males. Lastly, we show that the mSFI is enhanced in mouse models that show accelerated biological aging such as progeroid Ercc1 and Xpg mice of both sexes compared to age matched littermate wild types. In summary, the mSFI represents a novel index to quantify trajectories of biological aging in mice and may help elucidate links between impaired social behavior and the aging process.
存在多种方法来量化衰老过程并在个体层面估计生物学年龄。基于与年龄相关的身体缺陷积累的衰弱指数已被开发用于人类，并被转化为小鼠模型。然而，在衰老过程中观察到的衰退不仅限于身体功能，还涉及社交能力。“社交衰弱”的概念最近已被引入人类文献，但实验室小鼠尚无社交衰弱指数。为了填补这一空白，我们开发了一种小鼠社交衰弱指数（mSFI），它由七种不同的测定方法组成，旨在量化社交功能，执行起来相对简单且微创性最小。mSFI在群居雄性C57BL/6小鼠中的应用表明，在其整个生命周期中社交衰弱水平逐渐升高。相反，群居的雌性C57BL/6小鼠仅在非常老龄时才表现出社交衰弱。与雄性相比，雌性小鼠从10月龄起mSFI得分也显著更低。我们还将mSFI应用于处于慢性从属应激和慢性隔离状态的雄性C57BL/6小鼠，与年龄匹配的群居雄性相比，这两种情况均导致社交衰弱有更大幅度的增加。最后，我们表明，与年龄匹配的同窝野生型相比，在显示加速生物学衰老的小鼠模型中，如早衰的Ercc1和Xpg雌雄小鼠，mSFI增强。总之，mSFI代表了一种量化小鼠生物学衰老轨迹的新指数，可能有助于阐明社交行为受损与衰老过程之间的联系。
