Immunometabolic resistors of aging in long-lived golden spiny mice

Long-lived wild rodents closely related to laboratory mice on the evolutionary scale may allow identification of dormant pathways that resist aging. Spiny mice (<i>Acomys</i>) are known for their exceptional regenerative capacity, but their resilience to aging is unknown. Here, we report that aged golden spiny mice (<i>Acomys russatus</i>), reared in a non-pathogen-free environment, resist functional decline, have a greater repair capacity with reduced senescence in immune-metabolic organs compared to their sister species, eastern spiny mice (<i>Acomys dimidiatus</i>). Aged <i>A. russatus</i> maintains transcriptional integrity akin to young mice, highlighting experimental checkpoints for inflammation and mortality. We identified that elevated levels of clusterin in <i>A. russatus</i> macrophages restrain inflammaging and enhance health span in aged mice. Thus, <i>A. russatus</i> biology reveals therapeutically actionable targets that may enhance or maintain function during aging.