title: Perspective: Targeting the JAK/STAT pathway to fight age-related dysfunction.
abstract: Senescent cells accumulate in a variety of tissues with aging. They can develop a senescence-associated secretory phenotype (SASP) that entails secretion of inflammatory cytokines, chemokines, proteases, and growth factors. These SASP components can alter the microenvironment within tissues and affect the function of neighboring cells, which can eventually lead to local and systemic dysfunction. The JAK pathway is more highly activate in senescent than non-senescent cells. Inhibition of the JAK pathway suppresses the SASP in senescent cells and alleviates age-related tissue dysfunction. Targeting senescent cells could be a promising way to improve healthspan in aged population.
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, United States.
authors.forename: Tamar
authors.initials: T
authors.lastname: Tchkonia
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, United States. Electronic address: Kirkland.james@mayo.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D060833:Cellular Microenvironment; D016922:Cellular Senescence / Q000187:drug effects; D015195:Drug Design; D016330:Frail Elderly; D000073496:Frailty / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000627:therapeutic use*; D053612:Janus Kinases / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D010641:Phenotype; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000075242:Janus Kinase Inhibitors; D050791:STAT Transcription Factors; D053612:Janus Kinases
keywords: Cellular senescence; Frailty; Insulin resistance; Senolytics