Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice

The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in the elderly. To examine this question, bilateral renal IRI was induced in old (24 months) mice three weeks after parabiosis model establishment. At 24 hours after IRI, compared to old wild-type mice, the old mice with IRI had significantly damaged renal histology, decreased renal function, increased oxidative stress, inflammation, and apoptosis. However, there was no increase in autophagy. Compared to old mice with IRI, old-old parabiosis mice with IRI did not show differences in renal histological damage, oxidative stress, inflammation, apoptosis, or autophagy, but did exhibit improved renal function. Compared to the old-old parabiosis mice with IRI, the old mice with IRI in the young (12 week)-old parabiosis showed less renal histological injury and better renal function. Renal oxidative stress, inflammation, and apoptosis were significantly decreased, and autophagy was significantly increased. Thus, a youthful systemic milieu may decrease oxidative stress, inflammation, and apoptosis, and increase autophagy in old mice with IRI. These effects ameliorated IRI injuries in old mice. Our study provides new ideas for effectively preventing and treating AKI in the elderly.