Boosting Mitochondrial Recycling Rejuvenates Hematopoietic and Immune Systems
Year: 2025
Type: dissertation
Abstract: Hematopoietic stem cells (HSCs) sustain lifelong blood and immune system homeostasis by generating all blood lineages. However, aging impairs HSC functionality, leading to a myeloid-biased differentiation and reduced lymphoid compartments. This compromises immune responses and increases susceptibility to infections and hematopoietic failure in elderly individuals. The accumulation of defective mitochondria and dysregulated mitochondrial metabolism has been associated with HSC aging, yet the causal relationship remains unclear. Here, we demonstrated that modulating mitochondrial recycling rejuvenated aged HSCs, restored their regenerative potential, and improved immune function. Our findings revealed that in vitro administration of Urolithin A, a mitophagy inducer, restored mitochondrial homeostasis and enhanced the blood reconstitution capabilities of aged HSCs. Additionally, dietary supplementation with Urolithin A improved bone marrow functionality, expanded lymphoid compartments, and strengthened immune responses against viral infections in aged mice. These rejuvenating effects were linked to the induction of mitophagy, which re-established mitochondrial fitness in aged HSCs, and slowing down proliferation, through SMAD3/4 downstream signaling. In summary, our study identified Urolithin A as a pivotal regulator of HSC aging and highlighted mitochondrial recycling as a promising therapeutic target to reverse hematopoietic and immune aging.
Source: IRIS
Author: Chiang, Yi-Hsuan
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7045610394