title: Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet.
abstract: Recent discoveries have revealed the key role of mTOR (target of rapamycin) in aging. Furthermore, rapamycin extends lifespan in mice, especially in female mice. Here, we treated obese male mice on high-fat diet with rapamycin given intermittently: either weekly (once a week) or alternating bi-weekly (three injections every other week). While only marginally reducing obesity, intermittent administration of rapamycin significantly extended lifespan. Significance was achieved for weekly treated group and for the three rapamycin-received groups combined. In weekly treatment group, 100% mice were alive by the age of 2 years, whereas 60% of mice died in untreated group by this age. The effect of weekly treatment on survival was highly significant and cannot be fully explained by partial reduction in obesity. Alternating bi-weekly treatments seem to be less effective than weekly treatment, although effects of additional factors (see ) may not be excluded. After one year of treatment, all survived mice were sacrificed 8 days after the last administration of rapamycin to avoid its direct interference with parameters examined. Fasting levels of cardiac and hepatic p-S6, a marker of mTORC1 activity, were lower in weekly treatment group compared with control mice. In contrast, levels of p-Akt (S473), glucose, triglycerides and insulin were unchanged, whereas leptin and IGF-1 tended to be lower. Thus, weekly treatment with rapamycin may slow down aging in obese male mice on high-fat diet.
authors.affiliation: Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Leontieva
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Paszkiewicz
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Blagosklonny
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D004334:Drug Administration Schedule; D005260:Female; D008136:Longevity / Q000187:drug effects; D008297:Male; D055442:Metabolome; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus / Q000008:administration & dosage* / Q000494:pharmacology*; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus
keywords: aging; anti-aging agent; longevity; mammalian or mechanistic target of rapamycin; mortality; obesity; rapamycin