Irisin and exercise activate renal anti-aging pathways and enhance survival in young mice: a translational insight into muscle-kidney crosstalk

Irisin, a myokine released by skeletal muscle during physical activity, has emerged as a key regulator of energy metabolism, cellular stress responses, and longevity pathways. While previous studies have focused on aged animal-models or pathological states, the long-term impact of early-life interventions on molecular aging pathways remains poorly understood. This study investigated whether early-life irisin administration and physical exercise could modulate the renal-expression of Klotho and HSP70—two hallmark genes of cellular protection and anti-aging in young adult NMRI mice. Animals underwent 8 weeks of resistance training, endurance training, or irisin injection. Plasma irisin was quantified via ELISA, and renal Klotho and HSP70 expression levels were assessed using qPCR and Western-blotting. All interventions significantly increased circulating irisin and upregulated Klotho and HSP70 at both transcriptional and protein levels, with resistance training inducing the most pronounced effects. A 20-month survival analysis showed a trend toward improved longevity in all intervention groups. These findings suggest that early-life exercise and irisin exposure may activate renoprotective and longevity-associated pathways before the onset of molecular aging, supporting their potential as preventive strategies in translational geroscience.