SIRT6 in DNA repair, metabolism and ageing.
Ageing, or increased mortality with time, coupled with physiologic decline, is a nearly universal yet poorly understood biological phenomenon. Studies in model organisms suggest that two conserved pathways modulate longevity: DNA damage repair and Insulin/Igf1-like signalling. In addition, homologs of yeast Sir2--the sirtuins--regulate lifespan in diverse organisms. Here, we focus on one particular sirtuin, SIRT6. Mice lacking SIRT6 develop a degenerative disorder that in some respects mimics models of accelerated ageing [Cell (2006) 124:315]. We discuss how sirtuins in general and SIRT6 specifically relate to other evolutionarily conserved pathways affecting ageing, and how SIRT6 might function to ensure organismal homeostasis and normal lifespan.
Lombard
D B
DB
Howard Hughes Medical Institute, The Children's Hospital, CBR Institute for Biomedical Research, Boston, MA, USA.
Schwer
B
B
Alt
F W
FW
Mostoslavsky
R
R
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004260:DNA Repair / Q000502:physiology*; D008136:Longevity; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010641:Phenotype; D037761:Sirtuins / Q000378:metabolism*
D037761:Sirtuins