title: Increased polyploidy in aortic vascular smooth muscle cells during aging is marked by cellular senescence.
abstract: We previously reported that the frequency of polyploid aortic vascular smooth muscle cells (VSMC) serves as a biomarker of aging. Cellular senescence of somatic cells is another marker of aging that is characterized by the inability to undergo cell division. Here, we examined whether polyploidy is associated with the development of cellular senescence in vivo. Analysis of aortic tissue preparations from young and old Brown Norway rats showed that expression of senescence markers such as p16(INK4a) and senescence-associated beta-galactosidase activity are detected primarily in the old tissues. VSMC from p16(INK4a) knockout and control mice display similar levels of polyploid cells. Intriguingly, senescence markers are expressed in most, but not all, polyploid VSMC. Moreover, the polyploid cells exhibit limited proliferative capacity in comparison to their diploid counterparts. This study is the first to demonstrate in vivo that polyploid VSMC adopt a senescent phenotype.
authors.affiliation: Department of Biochemistry and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Donald J
authors.initials: DJ
authors.lastname: McCrann
authors.forename: Hao
authors.initials: H
authors.lastname: Nguyen
authors.forename: Cynthia
authors.initials: C
authors.lastname: St Hilaire
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DePinho
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jones
authors.forename: Katya
authors.initials: K
authors.lastname: Ravid
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D016922:Cellular Senescence; D008858:Microscopy, Phase-Contrast; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011123:Polyploidy; D051381:Rats
chemical_list: D015415:Biomarkers