Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

被引:21
作者
Yen, Kelvin [1 ]
Mobbs, Charles V. [2 ]
机构
[1] Univ Massachusetts, Sch Med, Worcester, MA 01606 USA
[2] Mt Sinai Sch Med, New York, NY 10029 USA
关键词
Caenorhabditis elegans; Aging; Lifespan; Gompertz analysis; GENE-EXPRESSION PROFILE; INCREASED LIFE-SPAN; DIETARY-RESTRICTION; OXIDATIVE STRESS; C-ELEGANS; METABOLIC-RATE; CALORIC RESTRICTION; SIGNALING PATHWAY; INSULIN-RECEPTOR; WILD-TYPE;
D O I
10.1007/s11357-009-9110-7
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Cold temperature, dietary restriction, reduced insulin/insulin-like growth factor signaling, and mutations in mitochondrial genes have all been shown to extend the lifespan of Caenorhabditis elegans (Kenyon et al., Nature 366:461-464, 1993; Klass, Mech Ageing Dev 6:413-429, 1977; Lakowski and Hekimi, Science 272:1010-1013, 1996). Additionally, all of them extend the lifespan of mice (Bluher et al., Science 299:572-574, 2003; Conti et al., Science 314:825-828, 2006; Holzenberger et al., Nature 421:182-187, 2003; Liu et al., Genes Dev 19:2424-2434, 2005; Weindruch and Walford, Science 215:1415-1418, 1982). The mechanism by which these treatments extend lifespan is currently unknown, but our study uses an epistatic approach to show that these four manipulations are mainly additive in terms of lifespan. Classical interpretation of this data suggests that these manipulations are independent of each other. However, using a Gompertz mortality rate analysis, the maximum mortality rate doubling time can be achieved through the use of only dietary restriction and cold temperature, suggesting that the mechanisms by which cold temperature and caloric restriction extend lifespan are the only independent mechanisms.
引用
收藏
页码:39 / 49
页数:11
相关论文
共 75 条
[11]   Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein [J].
Clancy, DJ ;
Gems, D ;
Harshman, LG ;
Oldham, S ;
Stocker, H ;
Hafen, E ;
Leevers, SJ ;
Partridge, L .
SCIENCE, 2001, 292 (5514) :104-106
[12]   Transgenic mice with a reduced core body temperature have an increased life span [J].
Conti, Bruno ;
Sanchez-Alavez, Manuel ;
Winsky-Sommerer, Raphaelle ;
Morale, Maria Concetta ;
Lucero, Jacinta ;
Brownell, Sara ;
Fabre, Veronique ;
Huitron-Resendiz, Salvador ;
Henriksen, Steven ;
Zorrilla, Eric P. ;
de Lecea, Luis ;
Bartfai, Tamas .
SCIENCE, 2006, 314 (5800) :825-828
[13]   Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span [J].
Coschigano, KT ;
Holland, AN ;
Riders, ME ;
List, EO ;
Flyvbjerg, A ;
Kopchick, JJ .
ENDOCRINOLOGY, 2003, 144 (09) :3799-3810
[14]   Lifespan regulation by evolutionarily conserved genes essential for viability [J].
Curran, Sean P. ;
Ruvkun, Gary .
PLOS GENETICS, 2007, 3 (04) :0479-0487
[15]   DIFFERENTIAL-EFFECTS OF DIETARY CALORIC AND PROTEIN RESTRICTION IN THE AGING RAT [J].
DAVIS, TA ;
BALES, CW ;
BEAUCHENE, RE .
EXPERIMENTAL GERONTOLOGY, 1983, 18 (06) :427-435
[16]   Rates of behavior and aging specified by mitochondrial function during development [J].
Dillin, A ;
Hsu, AL ;
Arantes-Oliveira, NA ;
Lehrer-Graiwer, J ;
Hsin, H ;
Fraser, AG ;
Kamath, RS ;
Ahringer, J ;
Kenyon, C .
SCIENCE, 2002, 298 (5602) :2398-2401
[17]   Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans [J].
Doonan, Ryan ;
McElwee, Joshua J. ;
Matthijssens, Filip ;
Walker, Glenda A. ;
Houthoofd, Koen ;
Back, Patricia ;
Matscheski, Andrea ;
Vanfleteren, Jacques R. ;
Gems, David .
GENES & DEVELOPMENT, 2008, 22 (23) :3236-3241
[18]  
Eliason SR, 1993, Maximum likelihood estimation: Logic and practice
[19]   Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1 [J].
Ewbank, JJ ;
Barnes, TM ;
Lakowski, B ;
Lussier, M ;
Bussey, H ;
Hekimi, S .
SCIENCE, 1997, 275 (5302) :980-983
[20]   Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans [J].
Feng, JL ;
Bussière, F ;
Hekimi, S .
DEVELOPMENTAL CELL, 2001, 1 (05) :633-644