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.


Originally published in Science Express on 2 February 2006
Science 3 March 2006:
Vol. 311. no. 5765, p. 1257
DOI: 10.1126/science.1122446

Brevia

Cellular Senescence in Aging Primates

Utz Herbig,1 Mark Ferreira,1 Laura Condel,2 Dee Carey,2 John M. Sedivy1*

The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status.

1 Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02903, USA.
2 Department of Comparative Medicine, Southwest Foundation for Biomedical Research, San Antonio, TX 78245, USA.

* To whom correspondence should be addressed. E-mail: john_sedivy{at}brown.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A quantitative model for age-dependent expression of the p16INK4a tumor suppressor.
D. Tsygankov, Y. Liu, H. K. Sanoff, N. E. Sharpless, and T. C. Elston (2009)
PNAS 106, 16562-16567
   Abstract »    Full Text »    PDF »
Developmental studies of Xenopus shelterin complexes: the message to reset telomere length is already present in the egg.
D. Vizlin-Hodzic, J. Ryme, S. Simonsson, and T. Simonsson (2009)
FASEB J 23, 2587-2594
   Abstract »    Full Text »    PDF »
Association Between Telomere Length, Specific Causes of Death, and Years of Healthy Life in Health, Aging, and Body Composition, a Population-Based Cohort Study.
O. T. Njajou, W.-C. Hsueh, E. H. Blackburn, A. B. Newman, S.-H. Wu, R. Li, E. M. Simonsick, T. M. Harris, S. R. Cummings, R. M. Cawthon, et al. (2009)
J Gerontol A Biol Sci Med Sci 64A, 860-864
   Abstract »    Full Text »    PDF »
Diphosphoinositol Polyphosphates: Metabolic Messengers?.
S. B. Shears (2009)
Mol. Pharmacol. 76, 236-252
   Abstract »    Full Text »    PDF »
Telomere dynamics rather than age predict life expectancy in the wild.
P. Bize, F. Criscuolo, N. B Metcalfe, L. Nasir, and P. Monaghan (2009)
Proc R Soc B 276, 1679-1683
   Abstract »    Full Text »    PDF »
BMP4 Mediates Oxidative Stress-induced Retinal Pigment Epithelial Cell Senescence and Is Overexpressed in Age-related Macular Degeneration.
D. Zhu, J. Wu, C. Spee, S. J. Ryan, and D. R. Hinton (2009)
J. Biol. Chem. 284, 9529-9539
   Abstract »    Full Text »    PDF »
Obesity Increases Vascular Senescence and Susceptibility to Ischemic Injury Through Chronic Activation of Akt and mTOR.
C.-Y. Wang, H.-H. Kim, Y. Hiroi, N. Sawada, S. Salomone, L. E. Benjamin, K. Walsh, M. A. Moskowitz, and J. K. Liao (2009)
Science Signaling 2, ra11
   Abstract »    Full Text »    PDF »
Human UBN1 Is an Ortholog of Yeast Hpc2p and Has an Essential Role in the HIRA/ASF1a Chromatin-Remodeling Pathway in Senescent Cells.
G. Banumathy, N. Somaiah, R. Zhang, Y. Tang, J. Hoffmann, M. Andrake, H. Ceulemans, D. Schultz, R. Marmorstein, and P. D. Adams (2009)
Mol. Cell. Biol. 29, 758-770
   Abstract »    Full Text »    PDF »
Senescent Stromal-Derived Osteopontin Promotes Preneoplastic Cell Growth.
E. Pazolli, X. Luo, S. Brehm, K. Carbery, J.-J. Chung, J. L. Prior, J. Doherty, S. Demehri, L. Salavaggione, D. Piwnica-Worms, et al. (2009)
Cancer Res. 69, 1230-1239
   Abstract »    Full Text »    PDF »
Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence.
P. Rai, T. T. Onder, J. J. Young, J. L. McFaline, B. Pang, P. C. Dedon, and R. A. Weinberg (2009)
PNAS 106, 169-174
   Abstract »    Full Text »    PDF »
Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease.
H. Jiang, E. Schiffer, Z. Song, J. Wang, P. Zurbig, K. Thedieck, S. Moes, H. Bantel, N. Saal, J. Jantos, et al. (2008)
PNAS 105, 11299-11304
   Abstract »    Full Text »    PDF »
Permanent embryo arrest: molecular and cellular concepts.
D.H. Betts and P. Madan (2008)
Mol. Hum. Reprod. 14, 445-453
   Abstract »    Full Text »    PDF »
CHIP Deficiency Decreases Longevity, with Accelerated Aging Phenotypes Accompanied by Altered Protein Quality Control.
J.-N. Min, R. A. Whaley, N. E. Sharpless, P. Lockyer, A. L. Portbury, and C. Patterson (2008)
Mol. Cell. Biol. 28, 4018-4025
   Abstract »    Full Text »    PDF »
Protumorigenic Effects of the Senescence-Associated Secretory Phenotype.
J. Campisi (2008)
Am. Assoc. Cancer Res. Educ. Book 2008, 505-509
   Abstract »    Full Text »    PDF »
UVB-induced Senescence in Human Keratinocytes Requires a Functional Insulin-like Growth Factor-1 Receptor and p53.
D. A. Lewis, Q. Yi, J. B. Travers, and D. F Spandau (2008)
Mol. Biol. Cell 19, 1346-1353
   Abstract »    Full Text »    PDF »
Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion.
C. L. Montes, A. I. Chapoval, J. Nelson, V. Orhue, X. Zhang, D. H. Schulze, S. E. Strome, and B. R. Gastman (2008)
Cancer Res. 68, 870-879
   Abstract »    Full Text »    PDF »
Telomeres and Longevity: Testing an Evolutionary Hypothesis.
M. F. Haussmann and R. A. Mauck (2008)
Mol. Biol. Evol. 25, 220-228
   Abstract »    Full Text »    PDF »
Contributions of DNA interstrand cross-links to aging of cells and organisms.
J. Grillari, H. Katinger, and R. Voglauer (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
DNA damage, cellular senescence and organismal ageing: causal or correlative?.
J.-H. Chen, C. N. Hales, and S. E. Ozanne (2007)
Nucleic Acids Res. 35, 7417-7428
   Abstract »    Full Text »    PDF »
DNA damage in telomeres and mitochondria during cellular senescence: is there a connection?.
J. F. Passos, G. Saretzki, and T. von Zglinicki (2007)
Nucleic Acids Res. 35, 7505-7513
   Abstract »    Full Text »    PDF »
Telomere length is paternally inherited and is associated with parental lifespan.
O. T. Njajou, R. M. Cawthon, C. M. Damcott, S.-H. Wu, S. Ott, M. J. Garant, E. H. Blackburn, B. D. Mitchell, A. R. Shuldiner, and W.-C. Hsueh (2007)
PNAS 104, 12135-12139
   Abstract »    Full Text »    PDF »
Mechanisms of Cardiovascular Disease in Accelerated Aging Syndromes.
B. C. Capell, F. S. Collins, and E. G. Nabel (2007)
Circ. Res. 101, 13-26
   Abstract »    Full Text »    PDF »
Senescence As an Anticancer Mechanism.
P. J. Hornsby (2007)
J. Clin. Oncol. 25, 1852-1857
   Abstract »    Full Text »    PDF »
Telomere Dynamics in Macaques and Humans.
J. P. Gardner, M. Kimura, W. Chai, J. F. Durrani, L. Tchakmakjian, X. Cao, X. Lu, G. Li, A. P. Peppas, J. Skurnick, et al. (2007)
J. Gerontol. A Biol. Sci. Med. Sci. 62, 367-374
   Abstract »    Full Text »    PDF »
WRN at telomeres: implications for aging and cancer.
A. S. Multani and S. Chang (2007)
J. Cell Sci. 120, 713-721
   Abstract »    Full Text »    PDF »
Cell Divisions Are Required for L1 Retrotransposition.
X. Shi, A. Seluanov, and V. Gorbunova (2007)
Mol. Cell. Biol. 27, 1264-1270
   Abstract »    Full Text »    PDF »
Vascular Cell Senescence: Contribution to Atherosclerosis.
T. Minamino and I. Komuro (2007)
Circ. Res. 100, 15-26
   Abstract »    Full Text »    PDF »
An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations.
K. C. Kregel and H. J. Zhang (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R18-R36
   Abstract »    Full Text »    PDF »
The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis.
G. Yang, D. G. Rosen, Z. Zhang, R. C. Bast Jr., G. B. Mills, J. A. Colacino, I. Mercado-Uribe, and J. Liu (2006)
PNAS 103, 16472-16477
   Abstract »    Full Text »    PDF »
Lamin A-Dependent Nuclear Defects in Human Aging.
P. Scaffidi and T. Misteli (2006)
Science 312, 1059-1063
   Abstract »    Full Text »    PDF »
Cellular-Aging Markers Linked to Aging of Primates.
(2006)
Journal Watch Dermatology 2006, 2
   Full Text »
Cellular-Aging Markers Linked to Aging of Primates.
(2006)
Journal Watch (General) 2006, 8
   Full Text »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)