Mitigating effects of aging on human health remains elusive because aging impacts multiple systems simultaneously, and because experimental animals exhibit critical aging differences relative to humans. Separation of aging into discrete processes may identify targetable drivers of pathology, particularly when applied to human-specific features. Gradual homeostatic expansion of CD8 T cells dominantly alters their function in aging humans but not in mice. Injecting T cells into athymic mice induces rapid homeostatic expansion, but its relevance to aging remains uncertain. We hypothesized that homeostatic expansion of T cells injected into T-deficient hosts models physiologically relevant CD8 T cell aging in young mice, and aimed to analyze age-related T cell phenotype and tissue pathology in such animals. Indeed, we found that such injection conferred uniform age-related phenotype, genotype, and function to mouse CD8 T cells, heightened age-associated tissue pathology in young athymic hosts, and humanized amyloidosis after brain injury in secondary wild-type recipients. This validates a model conferring a human-specific aging feature to mice that identifies targetable drivers of tissue pathology. Similar examination of independent aging features should promote systematic understanding of aging and identify additional targets to mitigate its effects on human health.

减缓衰老对人类健康的影响仍然难以捉摸，因为衰老同时影响多个系统，而且实验动物相对于人类表现出关键的衰老差异。将衰老分为离散过程可以识别病理学的可靶向驱动因素，特别是当应用于人类特定特征时。CD8 T 细胞的逐渐稳态扩张主要改变了它们在衰老人类中的功能，但在小鼠中没有。将 T 细胞注射到无胸腺小鼠体内可诱导快速稳态扩张，但其与衰老的相关性仍不确定。我们假设注射到 T 缺陷宿主中的 T 细胞的稳态扩增模拟了年轻小鼠生理相关的 CD8 T 细胞衰老，并旨在分析这些动物中与年龄相关的 T 细胞表型和组织病理学。的确，我们发现这种注射赋予小鼠 CD8 T 细胞一致的年龄相关表型、基因型和功能，增强年轻无胸腺宿主的年龄相关组织病理学，以及继发野生型受体脑损伤后的人源化淀粉样变性。这验证了一个模型，该模型赋予小鼠特定于人类的衰老特征，可识别组织病理学的可靶向驱动因素。对独立衰老特征的类似检查应促进对衰老的系统理解，并确定其他目标以减轻其对人类健康的影响。这验证了赋予小鼠特定于人类的衰老特征的模型，该模型可识别组织病理学的可靶向驱动因素。对独立衰老特征的类似检查应促进对衰老的系统理解，并确定其他目标以减轻其对人类健康的影响。这验证了赋予小鼠特定于人类的衰老特征的模型，该模型可识别组织病理学的可靶向驱动因素。对独立衰老特征的类似检查应促进对衰老的系统理解，并确定其他目标以减轻其对人类健康的影响。