Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems

Aging compromises hematopoietic and immune system functions, making older adults especially susceptible to hematopoietic failure, infections and tumor development, and thus representing an important medical target for a broad range of diseases. During aging, hematopoietic stem cells (HSCs) lose their blood reconstitution capability and commit preferentially toward the myeloid lineage (myeloid bias)1,2. These processes are accompanied by an aberrant accumulation of mitochondria in HSCs3. The administration of the mitochondrial modulator urolithin A corrects mitochondrial function in HSCs and completely restores the blood reconstitution capability of ‘old’ HSCs. Moreover, urolithin A-supplemented food restores lymphoid compartments, boosts HSC function and improves the immune response against viral infection in old mice. Altogether our results demonstrate that boosting mitochondrial recycling reverts the aging phenotype in the hematopoietic and immune systems. Urolithin A (UA) is a gut microbiome-derived metabolite that has been therapeutically explored in aging-related diseases and exerts its benefits in part through effects on mitochondria. Here Girotra, Chiang and colleagues show that UA administration boosts mitochondrial recycling in hematopoietic stem cells and reverses aging features in both the hematopoietic and immune systems.