title: [Metformin slows down ageing processes at the cellular level in SHR mice].
abstract: It has been shown recently that metformin, the indirect mTOR-kinase inhibitor, significantly increases medium (by 37.8%) and maximum (by 10.3%) life span of SHR mice (Anisimov et al., 2008). We obtained fibroblasts from skin of 11-, 16-, 19- and 23-months-old SHR mice treated with metformin since the third and ninth day of life. We studied markers of cellular senescence in these fibroblasts. Significant differences were observed between the average number of senescence-associated heterochromatic foci (SAHF), the average of area nuclei and fluorescence intensity of nucleus after staining for gamma-H2AX in control and experimental animals. Also, we showed that metformin prevented the accumulation of fibroblasts with large area of nuclei; high activity of senescence-associated beta-galactosidase (SA-beta-gal), and high fluorescence intensity after staining for gamma-H2AX. It appears that accumulation of large quantity of senescence markers within a cell triggers it to enter the aging process. It appears that the increase of "old" cell population above the threshold disrupts the normal function of certain tissues, organs, and finally, the whole organism. It appears that metformin delays the "old" cells accumulation and prolongs the organism youth.
authors.forename: A V
authors.initials: AV
authors.lastname: Arkad'eva
authors.forename: A A
authors.initials: AA
authors.lastname: Mamonov
authors.forename: I G
authors.initials: IG
authors.lastname: Popovich
authors.forename: V N
authors.initials: VN
authors.lastname: Anisimov
authors.forename: V M
authors.initials: VM
authors.lastname: Mikhel'son
authors.forename: I M
authors.initials: IM
authors.lastname: Spivak
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D007004:Hypoglycemic Agents; D047428:Protein Kinase Inhibitors; D008687:Metformin; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases