title: Rapamycin additively extends lifespan in short- and long-lived lines of the nematode Caenorhabditis remanei.
abstract: Despite tremendous progress in finding genes that, when manipulated, affects lifespan, little is known about the genetics underlying natural variation in lifespan. While segregating genetic variants for lifespan has been notoriously difficult to find in genome-wide association studies (GWAS), a complementary approach is to manipulate key genetic pathways in lines that differ in lifespan. If these candidate pathways are down regulated in long-lived lines, these lines can be predicted to respond less to pharmaceutical down-regulation of these pathways than short-lived lines. Experimental studies have identified the nutrient-sensing pathway TOR as a key regulator of lifespan in model organisms, and this pathway can effectively be down regulated using the drug rapamycin, which extends lifespan in all tested species. We expose short- and long-lived lines of the nematode Caenorhabditis remanei to rapamycin, and investigate if long-lived lines, which are hypothesized to already have down-regulated TOR signaling, respond less to rapamycin. We found no interaction between line and rapamycin treatment, since rapamycin extended lifespan independent of the intrinsic lifespan of the lines. This shows that rapamycin is equally effective on long and short-lived lines, and suggests that the evolution of long life may involve more factors that down-regulation of TOR.
authors.affiliation: Ageing Research Group, Department of Animal Ecology, Evolutionary Biology Centre, Uppsala University, 752 36 Uppsala, Sweden. Electronic address: martin.i.lind@gmail.com.
authors.forename: Martin I
authors.initials: MI
authors.lastname: Lind
authors.affiliation: Ageing Research Group, Department of Animal Ecology, Evolutionary Biology Centre, Uppsala University, 752 36 Uppsala, Sweden.
authors.forename: Hwei-Yen
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Ageing Research Group, Department of Animal Ecology, Evolutionary Biology Centre, Uppsala University, 752 36 Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Cortazar-Chinarro
authors.affiliation: Ageing Research Group, Department of Animal Ecology, Evolutionary Biology Centre, Uppsala University, 752 36 Uppsala, Sweden.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Maklakov
mesh_terms: D000818:Animals; D002107:Caenorhabditis / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D014644:Genetic Variation; D015801:Helminth Proteins / Q000235:genetics; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D015801:Helminth Proteins; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Experimental evolution; Lifespan; Rapamycin; TOR