Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration

被引：824
作者：
Lin, SJ
Kaeberlein, M
Andalis, AA
Sturtz, LA
Defossez, PA
Culotta, VC
Fink, GR
Guarente, L
机构：
[1] MIT, Dept Biol, Cambridge, MA 02139 USA
[2] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[3] Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA
来源：
NATURE | 2002年 / 418卷 / 6895期
基金：
美国国家科学基金会;
关键词：
D O I：
10.1038/nature00829
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals(1-4). We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA)(5). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide)(5). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals.
引用
收藏
页码：344 / 348
页数：5
相关论文
共 29 条
[1]   Stoichiometry and compartmentation of NADH metabolism in Saccharomyces cerevisiae [J].
Bakker, BM ;
Overkamp, KM ;
van Maris, AJA ;
Kötter, P ;
Luttik, MAH ;
van Dijken, JP ;
Pronk, JT .
FEMS MICROBIOLOGY REVIEWS, 2001, 25 (01) :15-37
[2]   Redirection of the respiro-fermentative flux distribution in Saccharomyces cerevisiae by overexpression of the transcription factor Hap4p [J].
Blom, J ;
De Mattos, MJT ;
Grivell, LA .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2000, 66 (05) :1970-1973
[3]   GLOBAL REGULATION OF MITOCHONDRIAL BIOGENESIS IN SACCHAROMYCES-CEREVISIAE [J].
DEWINDE, JH ;
GRIVELL, LA .
PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 46, 1993, 46 :51-91
[4]   Cluster analysis and display of genome-wide expression patterns [J].
Eisen, MB ;
Spellman, PT ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14863-14868
[5]   Regulation of longevity and stress resistance by Sch9 in yeast [J].
Fabrizio, P ;
Pozza, F ;
Pletcher, SD ;
Gendron, CM ;
Longo, VD .
SCIENCE, 2001, 292 (5515) :288-290
[6]   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
[7]   IDENTIFICATION AND CHARACTERIZATION OF HAP4 - A 3RD COMPONENT OF THE CCAAT-BOUND HAP2 HAP3 HETEROMER [J].
FORSBURG, SL ;
GUARENTE, L .
GENES & DEVELOPMENT, 1989, 3 (08) :1166-1178
[8]  
Guarente L, 2000, GENE DEV, V14, P1021
[9]   A new efficient gene disruption cassette for repeated use in budding yeast [J].
Guldener, U ;
Heck, S ;
Fiedler, T ;
Beinhauer, J ;
Hegemann, JH .
NUCLEIC ACIDS RESEARCH, 1996, 24 (13) :2519-2524
[10]   A concise guide to cDNA microarray analysis [J].
Hegde, P ;
Qi, R ;
Abernathy, K ;
Gay, C ;
Dharap, S ;
Gaspard, R ;
Hughes, JE ;
Snesrud, E ;
Lee, N ;
Quackenbush, J .
BIOTECHNIQUES, 2000, 29 (03) :548-+
123