Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
The identification and study of long-lived mutant
animals has provided valuable insights into the mechanisms that limit
thelife-span of organisms. Findings with the gene SIR2
suggest thatthe rate of aging can be regulated under certain
conditions. Indeed,increased expression of SIR2 lengthens
life-span by acting onbiological processes that promote survival
under conditions ofscarcity. In addition, studies of mutant strains of
Caenorhabditiselegans, in particular daf-2,
clk-1, and isp-1 mutants, suggestthat the
biology of reactive oxygen species in the mitochondriaand elsewhere
might be the main determinant of life-span in thisorganism. Thus, the
aging process may be more specific than previouslyanticipated on
evolutionary grounds.
1 Department of Biology, McGill
University, Montreal, Quebec H3A 1B1, Canada.
2 Department of Biology, Massachusetts Institute of
Technology, Cambridge, MA 02139, USA.
*
To whom correspondence should be addressed. E-mail:
siegfried.hekimi{at}mcgill.ca
The editors suggest the following Related Resources on Science sites:
In Science Magazine
NEWS FOCUS
Laura Helmuth (28 February 2003) Science299 (5611), 1300.
[DOI: 10.1126/science.299.5611.1300] |Summary »|Full Text »|PDF »
BOOKS
Ashley I. Bush (28 February 2003) Science299 (5611), 1318.
[DOI: 10.1126/science.1079480] |Summary »|Full Text »|PDF »
BOOKS
Daniel Promislow (28 February 2003) Science299 (5611), 1319.
[DOI: 10.1126/science.1081622] |Summary »|Full Text »|PDF »
POLICY FORUM
Eric T. Juengst, Robert H. Binstock, Maxwell J. Mehlman, and Stephen G. Post (28 February 2003) Science299 (5611), 1323.
[DOI: 10.1126/science.1083135] |Summary »|Full Text »|PDF »
G. Li, Y.-F. Lee, S. Liu, Y. Cai, S. Xie, N.-C. Liu, B.-Y. Bao, Z. Chen, and C. Chang (2008)
Endocrinology
149, 3490-3499
|Abstract »|Full Text »|PDF »
Ginkgo biloba Extract EGb 761 and Wisconsin Ginseng Delay Sarcopenia in Caenorhabditis elegans.
Z. Cao, Y. Wu, K. Curry, Z. Wu, Y. Christen, and Y. Luo (2007)
J. Gerontol. A Biol. Sci. Med. Sci.
62, 1337-1345
|Abstract »|Full Text »|PDF »
A Measurable Increase in Oxidative Damage Due to Reduction in Superoxide Detoxification Fails to Shorten the Life Span of Long-Lived Mitochondrial Mutants of Caenorhabditis elegans.
GRO-{alpha}: A Potential Marker for Cancer and Aging Silenced by RNA Interference.
S. FIMMEL, L. DEVERMANN, A. HERRMANN, and C. ZOUBOULIS (2007)
Ann. N.Y. Acad. Sci.
1119, 176-189
|Abstract »|Full Text »|PDF »
Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104p.
N. Erjavec, L. Larsson, J. Grantham, and T. Nystrom (2007)
Genes & Dev.
21, 2410-2421
|Abstract »|Full Text »|PDF »
Changes in Histone Acetylation During Postovulatory Aging of Mouse Oocyte.
SIRT1 Gene, Age-Related Diseases, and Mortality: The Leiden 85-Plus Study.
M. Kuningas, M. Putters, R. G. J. Westendorp, P. E. Slagboom, and D. van Heemst (2007)
J. Gerontol. A Biol. Sci. Med. Sci.
62, 960-965
|Abstract »|Full Text »|PDF »
Cross-species microarray analysis with the OSCAR system suggests an INSR->Pax6->NQO1 neuro-protective pathway in aging and Alzheimer's disease.
Restructuring of the dinucleotide-binding fold in an NADP(H) sensor protein.
X. Zheng, X. Dai, Y. Zhao, Q. Chen, F. Lu, D. Yao, Q. Yu, X. Liu, C. Zhang, X. Gu, et al. (2007)
PNAS
104, 8809-8814
|Abstract »|Full Text »|PDF »
Decline in ribosomal fidelity contributes to the accumulation and stabilization of the master stress response regulator {sigma}S upon carbon starvation.
A. Fredriksson, M. Ballesteros, C. N. Peterson, O. Persson, T. J. Silhavy, and T. Nystrom (2007)
Genes & Dev.
21, 862-874
|Abstract »|Full Text »|PDF »
Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney.
B. Piotrkowski, C. G. Fraga, and E. M. V. de Cavanagh (2007)
Am J Physiol Regulatory Integrative Comp Physiol
292, R1494-R1501
|Abstract »|Full Text »|PDF »
Age-related influence on thiol, disulfide, and protein-mixed disulfide levels in human plasma..
D. Giustarini, I. Dalle-Donne, S. Lorenzini, A. Milzani, and R. Rossi (2006)
J. Gerontol. A Biol. Sci. Med. Sci.
61, 1030-1038
|Abstract »|Full Text »|PDF »
Mutations that increase the life span of C. elegans inhibit tumor growth..
J. M. Pinkston, D. Garigan, M. Hansen, and C. Kenyon (2006)
Science
313, 971-975
|Abstract »|Full Text »|PDF »
Endocrine signaling in Caenorhabditis elegans controls stress response and longevity..
R. Baumeister, E. Schaffitzel, and M. Hertweck (2006)
J. Endocrinol.
190, 191-202
|Abstract »|Full Text »|PDF »
Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice.
X. Liu, N. Jiang, B. Hughes, E. Bigras, E. Shoubridge, and S. Hekimi (2005)
Genes & Dev.
19, 2424-2434
|Abstract »|Full Text »|PDF »
A systematic RNAi screen for longevity genes in C. elegans.
B. Hamilton, Y. Dong, M. Shindo, W. Liu, I. Odell, G. Ruvkun, and S. S. Lee (2005)
Genes & Dev.
19, 1544-1555
|Abstract »|Full Text »|PDF »
Mouse Sir2 Homolog SIRT6 Is a Nuclear ADP-ribosyltransferase.
G. Liszt, E. Ford, M. Kurtev, and L. Guarente (2005)
J. Biol. Chem.
280, 21313-21320
|Abstract »|Full Text »|PDF »
Crystal Structure of a Nicotinate Phosphoribosyltransferase from Thermoplasma acidophilum.
D. H. Shin, N. Oganesyan, J. Jancarik, H. Yokota, R. Kim, and S.-H. Kim (2005)
J. Biol. Chem.
280, 18326-18335
|Abstract »|Full Text »|PDF »
Aging-associated changes in cardiac gene expression.
M. Volkova, R. Garg, S. Dick, and K. R. Boheler (2005)
Cardiovasc Res
66, 194-204
|Abstract »|Full Text »|PDF »
Conserved Locus-Specific Silencing Functions of Schizosaccharomyces pombe sir2+.
L. L. Freeman-Cook, E. B. Gomez, E. J. Spedale, J. Marlett, S. L. Forsburg, L. Pillus, and P. Laurenson (2005)
Genetics
169, 1243-1260
|Abstract »|Full Text »|PDF »
A more efficient search strategy for aging genes based on connectivity.
L. Ferrarini, L. Bertelli, J. Feala, A. D. McCulloch, and G. Paternostro (2005)
Bioinformatics
21, 338-348
|Abstract »|Full Text »|PDF »
Reversible Histone Acetylation and Deacetylation Mediate Genome-Wide, Promoter-Dependent and Locus-Specific Changes in Gene Expression During Plant Development.
L. Tian, M. P. Fong, J. J. Wang, N. E. Wei, H. Jiang, R. W. Doerge, and Z. J. Chen (2005)
Genetics
169, 337-345
|Abstract »|Full Text »|PDF »
Defective Mitochondrial Protein Translocation Precludes Normal Caenorhabditis elegans Development.
S. P. Curran, E. P. Leverich, C. M. Koehler, and P. L. Larsen (2004)
J. Biol. Chem.
279, 54655-54662
|Abstract »|Full Text »|PDF »
Sirviving Cardiac Stress: Cardioprotection Mediated by a Longevity Gene.
Silent Information Regulator 2{alpha}, a Longevity Factor and Class III Histone Deacetylase, Is an Essential Endogenous Apoptosis Inhibitor in Cardiac Myocytes.
R. R. Alcendor, L. A. Kirshenbaum, S.-i. Imai, S. F. Vatner, and J. Sadoshima (2004)
Circ. Res.
95, 971-980
|Abstract »|Full Text »|PDF »
Sir2 mediates longevity in the fly through a pathway related to calorie restriction.
Decreased Lifespan in the Absence of Expression of the Mitochondrial Small Heat Shock Protein Hsp22 in Drosophila.
G. Morrow, S. Battistini, P. Zhang, and R. M. Tanguay (2004)
J. Biol. Chem.
279, 43382-43385
|Abstract »|Full Text »|PDF »
A Functional Analysis Reveals Dependence on the Anaphase-Promoting Complex for Prolonged Life Span in Yeast.
T. A. A. Harkness, K. A. Shea, C. Legrand, M. Brahmania, and G. F. Davies (2004)
Genetics
168, 759-774
|Abstract »|Full Text »|PDF »
Coenzyme Specificity of Sir2 Protein Deacetylases: IMPLICATIONS FOR PHYSIOLOGICAL REGULATION.
M. T. Schmidt, B. C. Smith, M. D. Jackson, and J. M. Denu (2004)
J. Biol. Chem.
279, 40122-40129
|Abstract »|Full Text »|PDF »
Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase.
H. Y. Cohen, C. Miller, K. J. Bitterman, N. R. Wall, B. Hekking, B. Kessler, K. T. Howitz, M. Gorospe, R. de Cabo, and D. A. Sinclair (2004)
Science
305, 390-392
|Abstract »|Full Text »|PDF »
From the Cover: Mitochondrial "swirls" induced by oxygen stress and in the Drosophila mutant hyperswirl.
Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD+-dependent Sir2 histone/protein deacetylases.
K. Zhao, R. Harshaw, X. Chai, and R. Marmorstein (2004)
PNAS
101, 8563-8568
|Abstract »|Full Text »|PDF »
Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster.
G. N. Landis, D. Abdueva, D. Skvortsov, J. Yang, B. E. Rabin, J. Carrick, S. Tavare, and J. Tower (2004)
PNAS
101, 7663-7668
|Abstract »|Full Text »|PDF »
Cells have distinct mechanisms to maintain protection against different reactive oxygen species: Oxidative-stress-response genes.
G. W. Thorpe, C. S. Fong, N. Alic, V. J. Higgins, and I. W. Dawes (2004)
PNAS
101, 6564-6569
|Abstract »|Full Text »|PDF »
THE START OF ANTI-AGING MEDICINE?.
T. E. Johnson (2004)
Gerontologist
44, 270-273
|Full Text »|PDF »
Decreased expression of Cu-Zn superoxide dismutase 1 in ants with extreme lifespan.
J. D. Parker, K. M. Parker, B. H. Sohal, R. S. Sohal, and L. Keller (2004)
PNAS
101, 3486-3489
|Abstract »|Full Text »|PDF »
Yeast Life-Span Extension by Calorie Restriction Is Independent of NAD Fluctuation.
R. M. Anderson, M. Latorre-Esteves, A. R. Neves, S. Lavu, O. Medvedik, C. Taylor, K. T. Howitz, H. Santos, and D. A. Sinclair (2003)
Science
302, 2124-2126
|Abstract »|Full Text »|PDF »
Molecular Mechanism of Maternal Rescue in the clk-1 Mutants of Caenorhabditis elegans.
J. Burgess, A. K. Hihi, C. Y. Benard, R. Branicky, and S. Hekimi (2003)
J. Biol. Chem.
278, 49555-49562
|Abstract »|Full Text »|PDF »
SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response.
