title: Stress proteins in aging and life span.
abstract: Heat shock proteins (HSP) are molecular chaperones and have been implicated in longevity and aging in many species. Their major functions include chaperoning misfolded or newly synthesised polypeptides, protecting cells from proteotoxic stress, and processing of immunogenic agents. These proteins are expressed constitutively and can be induced by stresses such as heat, oxidative stress and many more. The induction of HSP in aging could potentially maintain protein homeostasis and longevity by refolding the damaged proteins which accumulate during aging and are toxic to cells. HSP are shown to increase life span in model organisms such as Caenorhabditis elegans and decrease aging-related proteotoxicity. Thus, decrease in HSP in aging is associated with disruption of cellular homeostasis which causes diseases such as cancer, cell senescence and neurodegeneration. HSP levels are decreased with aging in most organs including neurons. Aging also causes attenuation or alteration of many signalling pathways as well as the expression of transcription factors such as heat shock factor (HSF). The alteration in regulation and synthesis of Forkhead box O3a (FoxO3a) family of transcription factors as well as major antioxidant enzymes (manganese superoxide dismutase, catalase) are also seen in aging. Among many signalling mechanisms involved in altering longevity and aging, the insulin/IGF-1 pathway and the Sir2 deacetylase are highly significant. This review enquires into the role of some of these pathways in longevity/aging along with HSP.
authors.affiliation: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. amurshid@bidmc.harvard.edu
authors.forename: Ayesha
authors.initials: A
authors.lastname: Murshid
authors.forename: Takanori
authors.initials: T
authors.lastname: Eguchi
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Calderwood
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008136:Longevity / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D014157:Transcription Factors