title: Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.
abstract: Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span.
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN.
authors.forename: Marissa J
authors.initials: MJ
authors.lastname: Schafer
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: White
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN.
authors.forename: Glenda
authors.initials: G
authors.lastname: Evans
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Tonne
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, MN.
authors.forename: Grace C
authors.initials: GC
authors.lastname: Verzosa
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN Department of Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Stout
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mazula
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN.
authors.forename: Allyson K
authors.initials: AK
authors.lastname: Palmer
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Baker
authors.affiliation: Division of Endocrinology, Department of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jensen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN Department of Surgery, Mayo Clinic, Rochester, MN.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Miller
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tchkonia
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN Department of Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN lebrasseur.nathan@mayo.edu.
authors.forename: Nathan K
authors.initials: NK
authors.lastname: LeBrasseur
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000375:Aging / Q000502:physiology; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D057140:Fast Foods / Q000009:adverse effects*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase