title: Retinal aging and sirtuins.
abstract: The process of aging involves the accumulating changes in the microenvironment that lead to cell senescence or apoptosis, and subsequent tissue or organ dysfunction. Multiple extrinsic and intrinsic events that cause DNA instability are associated with aging. Cells containing unstable DNA are biologically vulnerable, and if the DNA damage is too great for the cell to repair, it becomes senescent or dies by apoptosis. Thus, the cell's capacity to repair its DNA determines the progress of aging, at least in part. Here, we focus on the sirtuins, the mammalian homologs of the yeast life-span-extending molecule, Sir2. Among the sirtuin family proteins in mammals, the one most similar to yeast Sir2 is SIRT1, which is involved in multiple pathways, including the repair of DNA double-strand breaks. Although the role of SIRT1 in mammalian longevity is not clear, it is expressed throughout the retina, where it may suppress aging. In fact, a mutant mouse model of retinal degeneration shows an abnormal subcellular localization of SIRT1 protein and accelerated retinal cell apoptosis. Further analyses are required to elucidate the mechanism of DNA damage and repair, including the contributions of the sirtuins, in the aged or diseased retinas, which will help us understand the mechanisms of retinal aging.
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan. yoko-o@sc.itc.keio.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kubota
authors.forename: Toshio
authors.initials: T
authors.lastname: Narimatsu
authors.forename: Kenya
authors.initials: K
authors.lastname: Yuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Koto
authors.forename: Mariko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D012160:Retina / Q000502:physiology*; D037761:Sirtuins / Q000502:physiology*
chemical_list: D037761:Sirtuins