DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and aging

被引:11
作者
Mostoslavsky, Raul [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02114 USA
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2008年 / 13卷
关键词
lifespan; cancer; sirtuins; SIRT6; genomic instability; DNA repair; DNA damage; insulin signaling; metabolic homeostasis; review;
D O I
10.2741/3203
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
For many years organismal aging and cancer were viewed as separate entities. Recent studies however have suggested that these two seemingly disparate biological processes may in fact share common biochemical pathways. One area of emerging convergence involves the intersection of pathways known to mediate DNA repair with pathways previously implicated in insulin signaling. Recent evidence suggests that the sirtuin family of proteins act as central mediators of this molecular crosstalk. The coordination of DNA repair with overall energy balance may be essential for reducing the risk of developing cancer as well as for determining the rate at which we age. This review will summarize our current knowledge on how the maintenance of genomic integrity and insulin signaling intersect, the potential regulation of sirtuins in this crosstalk, and how this coordinated regulation may have important implication for both tumor-free and overall survival.
引用
收藏
页码:6966 / 6990
页数:25
相关论文
共 229 条
[1]   Effect of caloric restriction on Hprt lymphocyte mutation in aging rats [J].
Aidoo, A ;
Mittelstaedt, RA ;
Bishop, ME ;
Lyn-Cook, LE ;
Chen, YJ ;
Duffy, P ;
Heflich, RH .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2003, 527 (1-2) :57-66
[2]   Long-lived growth hormone receptor knockout mice: Interaction of reduced insulin-like growth factor I/insulin signaling and caloric restriction [J].
Al-Regaiey, KA ;
Masternak, MM ;
Bonkowski, M ;
Sun, L ;
Bartke, A .
ENDOCRINOLOGY, 2005, 146 (02) :851-860
[3]   The overexpression of specialized DNA polymerases in cancer [J].
Albertella, MR ;
Lau, A ;
O'Connor, MJ .
DNA REPAIR, 2005, 4 (05) :583-593
[4]  
ALCENDOR RR, 2005, CELL METAB, V2, P67
[5]   Perturbations of the AKT signaling pathway in human cancer [J].
Altomare, DA ;
Testa, JR .
ONCOGENE, 2005, 24 (50) :7455-7464
[6]   Nucleotide excision repair disorders and the balance between cancer and aging [J].
Andressoo, Jaan-Olle ;
Hoeijmakers, Jan H. J. ;
Mitchell, James R. .
CELL CYCLE, 2006, 5 (24) :2886-2888
[7]   Altered sirtuin expression is associated with node-positive breast cancer [J].
Ashraf, N. ;
Zino, S. ;
MacIntyre, A. ;
Kingsmore, D. ;
Payne, A. P. ;
George, W. D. ;
Shiels, P. G. .
BRITISH JOURNAL OF CANCER, 2006, 95 (08) :1056-1061
[8]   Yeast cell-type regulation of DNA repair [J].
Äström, SU ;
Okamura, SM ;
Rine, J .
NATURE, 1999, 397 (6717) :310-310
[9]   Five repair pathways in one context: chromatin modification during DNA repair [J].
Ataian, Yeganeh ;
Krebs, Jocelyn E. .
BIOCHEMISTRY AND CELL BIOLOGY, 2006, 84 (04) :490-504
[10]   Mitochondria, oxidants, and aging [J].
Balaban, RS ;
Nemoto, S ;
Finkel, T .
CELL, 2005, 120 (04) :483-495