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.

Subscribe

Logo for

Science 310 (5756): 1954-1957

Copyright © 2005 by the American Association for the Advancement of Science

A Developmental Timing MicroRNA and Its Target Regulate Life Span in C. elegans

Michelle Boehm, and Frank Slack*

Abstract: The microRNA lin-4 and its target, the putative transcription factor lin-14, control the timing of larval development in Caenorhabditis elegans. Here, we report that lin-4 and lin-14 also regulate life span in the adult. Reducing the activity of lin-4 shortened life span and accelerated tissue aging, whereas overexpressing lin-4 or reducing the activity of lin-14 extended life span. Lifespan extension conferred by a reduction in lin-14 was dependent on the DAF-16 and HSF-1 transcription factors, suggesting that the lin-4lin-14 pair affects life span through the insulin/insulin-like growth factor–1 pathway. This work reveals a role for microRNAs and developmental timing genes in life-span regulation.

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.

* To whom correspondence should be addressed. E-mail: frank.slack{at}yale.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Impact of age-associated increase in 2'-O-methylation of miRNAs on aging and neurodegeneration in Drosophila.
M. Abe, A. Naqvi, G.-J. Hendriks, V. Feltzin, Y. Zhu, A. Grigoriev, and N. M. Bonini (2014)
Genes & Dev. 28, 44-57
   Abstract »    Full Text »    PDF »
Plant leaf senescence and death - regulation by multiple layers of control and implications for aging in general.
H. R. Woo, H. J. Kim, H. G. Nam, and P. O. Lim (2013)
J. Cell Sci. 126, 4823-4833
   Abstract »    Full Text »    PDF »
Aging-Induced Dysregulation of Dicer1-Dependent MicroRNA Expression Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells.
Z. Ungvari, Z. Tucsek, D. Sosnowska, P. Toth, T. Gautam, A. Podlutsky, A. Csiszar, G. Losonczy, M. N. Valcarcel-Ares, W. E. Sonntag, et al. (2013)
J Gerontol A Biol Sci Med Sci 68, 877-891
   Abstract »    Full Text »    PDF »
Developmental Decline in Neuronal Regeneration by the Progressive Change of Two Intrinsic Timers.
Y. Zou, H. Chiu, A. Zinovyeva, V. Ambros, C.-F. Chuang, and C. Chang (2013)
Science 340, 372-376
   Abstract »    Full Text »    PDF »
MicroRNAs in age-related diseases.
S. Dimmeler and P. Nicotera (2013)
EMBO Mol Med. 5, 180-190
   Abstract »    Full Text »    PDF »
A Steroid Receptor-MicroRNA Switch Regulates Life Span in Response to Signals from the Gonad.
Y. Shen, J. Wollam, D. Magner, O. Karalay, and A. Antebi (2012)
Science 338, 1472-1476
   Abstract »    Full Text »    PDF »
Post-developmental microRNA expression is required for normal physiology, and regulates aging in parallel to insulin/IGF-1 signaling in C. elegans.
N. J. Lehrbach, C. Castro, K. J. Murfitt, C. Abreu-Goodger, J. L. Griffin, and E. A. Miska (2012)
RNA 18, 2220-2235
   Abstract »    Full Text »    PDF »
Programmatic features of aging originating in development: aging mechanisms beyond molecular damage?.
J. P. de Magalhaes (2012)
FASEB J 26, 4821-4826
   Abstract »    Full Text »    PDF »
The lin-4 MicroRNA Targets the LIN-14 Transcription Factor to Inhibit Netrin-Mediated Axon Attraction.
Y. Zou, H. Chiu, D. Domenger, C.-F. Chuang, and C. Chang (2012)
Science Signaling 5, ra43
   Abstract »    Full Text »    PDF »
Discrepant Expression of MicroRNAs in Transparent and Cataractous Human Lenses.
C. Wu, H. Lin, Q. Wang, W. Chen, H. Luo, W. Chen, and H. Zhang (2012)
Invest. Ophthalmol. Vis. Sci. 53, 3906-3912
   Abstract »    Full Text »    PDF »
MicroRNAs and their roles in aging.
T. Smith-Vikos and F. J. Slack (2012)
J. Cell Sci. 125, 7-17
   Abstract »    Full Text »    PDF »
Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans.
M. Kato, X. Chen, S. Inukai, H. Zhao, and F. J. Slack (2011)
RNA 17, 1804-1820
   Abstract »    Full Text »    PDF »
A growing molecular toolbox for the functional analysis of microRNAs in Caenorhabditis elegans.
J. Jo and A. Esquela-Kerscher (2011)
Briefings in Functional Genomics 10, 175-180
   Abstract »    Full Text »    PDF »
miR-335 and miR-34a Promote Renal Senescence by Suppressing Mitochondrial Antioxidative Enzymes.
X.-Y. Bai, Y. Ma, R. Ding, B. Fu, S. Shi, and X.-M. Chen (2011)
J. Am. Soc. Nephrol. 22, 1252-1261
   Abstract »    Full Text »    PDF »
Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53.
A. P. Ugalde, A. J. Ramsay, J. de la Rosa, I. Varela, G. Marino, J. Cadinanos, J. Lu, J. M. Freije, and C. Lopez-Otin (2011)
EMBO J. 30, 2219-2232
   Abstract »    Full Text »    PDF »
Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis.
M. J. Drummond, J. J. McCarthy, M. Sinha, H. M. Spratt, E. Volpi, K. A. Esser, and B. B. Rasmussen (2011)
Physiol Genomics 43, 595-603
   Abstract »    Full Text »    PDF »
The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans.
X. Huang, H. Zhang, and H. Zhang (2011)
Development 138, 2059-2068
   Abstract »    Full Text »    PDF »
MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain.
M. Somel, S. Guo, N. Fu, Z. Yan, H. Y. Hu, Y. Xu, Y. Yuan, Z. Ning, Y. Hu, C. Menzel, et al. (2010)
Genome Res. 20, 1207-1218
   Abstract »    Full Text »    PDF »
Epigenetic alterations in aging.
S. Gonzalo (2010)
J Appl Physiol 109, 586-597
   Abstract »    Full Text »    PDF »
The von Hippel Lindau Tumor Suppressor Limits Longevity.
R.-U. Muller, F. Fabretti, S. Zank, V. Burst, T. Benzing, and B. Schermer (2009)
J. Am. Soc. Nephrol. 20, 2513-2517
   Abstract »    Full Text »    PDF »
GeneSet2miRNA: finding the signature of cooperative miRNA activities in the gene lists.
A. V. Antonov, S. Dietmann, P. Wong, D. Lutter, and H. W. Mewes (2009)
Nucleic Acids Res. 37, W323-W328
   Abstract »    Full Text »    PDF »
Serotonin mediates a learned increase in attraction to high concentrations of benzaldehyde in aged C. elegans.
D. Tsui and D. van der Kooy (2008)
Learn. Mem. 15, 844-855
   Abstract »    Full Text »    PDF »
FOXO3A genotype is strongly associated with human longevity.
B. J. Willcox, T. A. Donlon, Q. He, R. Chen, J. S. Grove, K. Yano, K. H. Masaki, D. C. Willcox, B. Rodriguez, and J. D. Curb (2008)
PNAS 105, 13987-13992
   Abstract »    Full Text »    PDF »
C. elegans dauer formation and the molecular basis of plasticity.
N. Fielenbach and A. Antebi (2008)
Genes & Dev. 22, 2149-2165
   Abstract »    Full Text »    PDF »
Functional genomic, computational and proteomic analysis of C. elegans microRNAs.
N. J. Lehrbach and E. A. Miska (2008)
Briefings in Functional Genomics
   Abstract »    Full Text »    PDF »
Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/{beta}-secretase expression.
S. S. Hebert, K. Horre, L. Nicolai, A. S. Papadopoulou, W. Mandemakers, A. N. Silahtaroglu, S. Kauppinen, A. Delacourte, and B. De Strooper (2008)
PNAS 105, 6415-6420
   Abstract »    Full Text »    PDF »
Quantitative evidence for conserved longevity pathways between divergent eukaryotic species.
E. D. Smith, M. Tsuchiya, L. A. Fox, N. Dang, D. Hu, E. O. Kerr, E. D. Johnston, B. N. Tchao, D. N. Pak, K. L. Welton, et al. (2008)
Genome Res. 18, 564-570
   Abstract »    Full Text »    PDF »
Reactivation of {gamma}HV68 induces neointimal lesions in pulmonary arteries of S100A4/Mts1-overexpressing mice in association with degradation of elastin.
E. Spiekerkoetter, C. M. Alvira, Y.-M. Kim, A. Bruneau, K. L. Pricola, L. Wang, N. Ambartsumian, and M. Rabinovitch (2008)
Am J Physiol Lung Cell Mol Physiol 294, L276-L289
   Abstract »    Full Text »    PDF »
Endostyle Cell Recruitment as a Frame of Reference for Development and Growth in the Urochordate Oikopleura dioica.
C. Troedsson, P. Ganot, J.-M. Bouquet, D. L. Aksnes, and E. M. Thompson (2007)
Biol. Bull. 213, 325-334
   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.
W. Yang, J. Li, and S. Hekimi (2007)
Genetics 177, 2063-2074
   Abstract »    Full Text »    PDF »
Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants.
A. V. Samuelson, C. E. Carr, and G. Ruvkun (2007)
Genes & Dev. 21, 2976-2994
   Abstract »    Full Text »    PDF »
The let-7 MicroRNA Represses Cell Proliferation Pathways in Human Cells.
C. D. Johnson, A. Esquela-Kerscher, G. Stefani, M. Byrom, K. Kelnar, D. Ovcharenko, M. Wilson, X. Wang, J. Shelton, J. Shingara, et al. (2007)
Cancer Res. 67, 7713-7722
   Abstract »    Full Text »    PDF »
Frailty in Relation to the Accumulation of Deficits.
K. Rockwood and A. Mitnitski (2007)
J Gerontol A Biol Sci Med Sci 62, 722-727
   Abstract »    Full Text »    PDF »
Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency.
A. Polesskaya, S. Cuvellier, I. Naguibneva, A. Duquet, E. G. Moss, and A. Harel-Bellan (2007)
Genes & Dev. 21, 1125-1138
   Abstract »    Full Text »    PDF »
A Demographic Analysis of the Fitness Cost of Extended Longevity in Caenorhabditis elegans.
J. Chen, D. Senturk, J.-L. Wang, H.-G. Muller, J. R. Carey, H. Caswell, and E. P. Caswell-Chen (2007)
J Gerontol A Biol Sci Med Sci 62, 126-135
   Abstract »    Full Text »    PDF »
MicroRNAs in biological processes and carcinogenesis.
H. Osada and T. Takahashi (2007)
Carcinogenesis 28, 2-12
   Abstract »    Full Text »    PDF »
Aging on the clock.
A. Katsnelson (2006)
J. Cell Biol. 172, 327b
   Full Text »    PDF »
MicroRNA Function and Mechanism: Insights from Zebra Fish.
A.F. SCHIER and A.J. GIRALDEZ (2006)
Cold Spring Harb Symp Quant Biol 71, 195-203
   Abstract »    PDF »
PHYSIOLOGY: The Tick-Tock of Aging?.
A. Antebi (2005)
Science 310, 1911-1913
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882