Proteomic changes induced by longevity-promoting interventions in mice.
Publication Title
Geroscience
Document Type
Article
Publication Date
4-1-2024
Keywords
washington; isb; Mice; Animals; Longevity; Proteome; Proteomics; Transcription Factors; Receptors, Somatotropin
Abstract
Using mouse models and high-throughput proteomics, we conducted an in-depth analysis of the proteome changes induced in response to seven interventions known to increase mouse lifespan. This included two genetic mutations, a growth hormone receptor knockout (GHRKO mice) and a mutation in the Pit-1 locus (Snell dwarf mice), four drug treatments (rapamycin, acarbose, canagliflozin, and 17a-estradiol), and caloric restriction. Each of the interventions studied induced variable changes in the concentrations of proteins across liver, kidney, and gastrocnemius muscle tissue samples, with the strongest responses in the liver and limited concordance in protein responses across tissues. To the extent that these interventions promote longevity through common biological mechanisms, we anticipated that proteins associated with longevity could be identified by characterizing shared responses across all or multiple interventions. Many of the proteome alterations induced by each intervention were distinct, potentially implicating a variety of biological pathways as being related to lifespan extension. While we found no protein that was affected similarly by every intervention, we identified a set of proteins that responded to multiple interventions. These proteins were functionally diverse but tended to be involved in peroxisomal oxidation and metabolism of fatty acids. These results provide candidate proteins and biological mechanisms related to enhancing longevity that can inform research on therapeutic approaches to promote healthy aging.
Specialty/Research Institute
Institute for Systems Biology
Specialty/Research Institute
Epidemiology
Specialty/Research Institute
Pathology & Laboratory Medicine
DOI
10.1007/s11357-023-00917-z
