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Entropy increases with increasing age before plateauing at old age (21–24 months) in mice (top panel). This is concomitant with a decline in skeletal muscle function, which continues to progress into oldest-old age (second panel). We show that AAV-Kl administration can rescue muscle functional declines when administered to old mice (third panel), but this effect is lost when AAV-Klotho is delivered to oldest-old (27–29 months) mice (bottom panel).
