The longevity effects of reduced IGF-1 signaling depend on the stability of the mitochondrial genome
Year: 2026
Type: article
Abstract: Suppression of insulin-like growth factor-1 (IGF-1) signaling extends mammalian lifespan and protects against a range of age-related diseases. Surprisingly though, we found that reduced IGF-1 signaling fails to extend the lifespan of mitochondrial mutator mice. Accordingly, most of the longevity pathways that are normally initiated by IGF-1 suppression were either blocked or blunted in the mutator mice. These observations suggest that the pro-longevity effects of IGF-1 suppression critically depend on the integrity of the mitochondrial genome and that mitochondrial mutations may impose a hard limit on mammalian lifespan. Together, these findings deepen our understanding of the interactions between the hallmarks of aging and underscore the need for interventions that preserve the integrity of the mitochondrial genome.
Source: Science Advances
Authors: Sarah J. Shemtov, Eric McGann, Lucy Carrillo, Sangmin Lee, Herbert Anson, Eric Hwang, Claire S. Chung, Jaye L. Weinert, Maria-Eleni Anagnostou, Guan-Ju D. Lai, Bert M. Verheijen, Junxiang Wan, Ivetta Vorobyova, Monica Sanchez-Contreras, Cheryl A. Conover, Max A. Thorwald, Pinchas Cohen, Scott R. Kennedy, Jean-François Gout, Suraiya Haroon, Marc Vermulst
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: Triggering the Selective Removal of Deleterious mtDNA Mutations from Mammalian Cells, G5283476803, Targeting the IGF-1/insulin signaling pathway to treat mtDNA disease, Investigating the landscape and genetic architecture of germline mutagenesis, DNA-damage-induced transcription errors provide a constant stream of amyloid and prion-like proteins in human cells, Temporal control of mitochondrial mutagenesis, Understanding the regulation of mtDNA heteroplasmy and integrity
OpenAlex ID: W7148986725