Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes

Campisi, Judith

doi:10.1016/s0531-5565(02)00152-3

Cited by 190 publications

(126 citation statements)

References 71 publications

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“…Decreased levels of Hsp90 during aging may also contribute to altered growth factor responses and increased cellular senescence and therefore increased risk of older age-onset OA. In most somatic cell populations, abnormal protein synthesis and altered growth factor responses appear well in advance of cell growth arrest (45). Results of studies focusing on chondrocyte senescence have suggested that chondrocytes begin to lose their ability to maintain articular cartilage ECM well before they reach replicative senescence (46).…”

Section: Discussionmentioning

confidence: 99%

Hsp90 mediates insulin‐like growth factor 1 and interleukin‐1β signaling in an age‐dependent manner in equine articular chondrocytes

Boehm¹,

Seth²,

Mayr³

et al. 2007

Arthritis & Rheumatism

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Objective. Many metabolic processes in chondrocytes thought to contribute to age-related changes in the extracellular matrix are influenced by known roles of Hsp90. Age-related decreases in the level of Hsp90 have been documented in numerous cell types and could contribute to cartilage degeneration. The aim of this study was to investigate the roles of age and Hsp90 in insulin-like growth factor 1 (IGF-1) and interleukin-1␤ (IL-1␤) signaling in chondrocytes.Methods. Levels of Hsp90 messenger RNA (mRNA) and protein, with respect to age, were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. The Hsp90 inhibitor geldanamycin (50 nM, 100 nM, or 500 nM) was used to assess age-related responses to Hsp90 with concurrent IGF-1 or IL-1␤ stimulation of chondrocytes. Quantitative real-time PCR was used to measure COL2A1 and matrix metalloproteinase 13 (MMP13) gene expression; Western blot analysis was performed to determine the phosphorylation status of p42/44 and Akt/protein kinase B.Results. The effects of Hsp90 inhibition with geldanamycin were concentration dependent. Inhibition of Hsp90 with 100 nM or 500 nM geldanamycin blocked IGF-1-induced cell proliferation, Akt and p42/44 activation, and COL2A1 expression. Basal and IL-1␤-induced up-regulation of MMP13 mRNA was blocked by all concentrations of geldanamycin tested. Gain-offunction assays with Hsp90 resulted in increased expression of MMP13 mRNA.Conclusion. These results suggest that Hsp90 is involved in opposing signaling pathways of cartilage homeostasis, and that catabolic responses are more sensitive to Hsp90 inhibition than are anabolic responses. Further studies are needed to determine the role of Hsp90 inhibition in osteoarthritis in order to assess its potential as a therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Hsp90 mediates insulin‐like growth factor 1 and interleukin‐1β signaling in an age‐dependent manner in equine articular chondrocytes

Boehm¹,

Seth²,

Mayr³

et al. 2007

Arthritis & Rheumatism

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“…On the other hand, apoptosis can eventually deplete tissues of their constituent cells and/or deplete the stem cell pools that replenish renewable tissues (Joaquin and Gollapudi, 2001;Weinstein and Ciszek, 2002;Zhang and Herman, 2002;Campisi, 2003aCampisi, , 2003b. Hence, with increasing age, apoptosis might cause an overall loss of tissue structure and function, a hallmark of aging.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

“…However, with increasing age, senescent cells, which are incapable of regeneration and show marked changes in function (discussed below), can accumulate. Again, this accumulation can lead to an overall loss of tissue structure and function (Campisi, 1996(Campisi, , 2003a(Campisi, , 2003bSmith and Pereira-Smith, 1996;Faragher, 2000). Like apoptosis, cellular senescence may contribute to the degenerative diseases of aging.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

“…Like apoptosis, cellular senescence may contribute to the degenerative diseases of aging. In addition, because the secretory phenotype of senescent cells can alter the local tissue milieu, senescent cells may also contribute to the hyperproliferative diseases of aging, including-ironically-cancer (Campisi, 1997(Campisi, , 2003a(Campisi, , 2003b.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

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Aging, tumor suppression and cancer: high wire-act!

Campisi

2005

Mechanisms of Ageing and Development

155

120

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Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responsesapoptosis or senescence-that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation. We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropyprotecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms. # 2004 Published by Elsevier Ireland Ltd.

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“…Similar to yeast replicative aging, as cell division occurs in vitro, eventually the ability to replicate is lost and a wide variety of related biochemical changes occur (Cristofalo, 1997). It has been proposed that cellular senescence is critical for suppressing tumorigenesis in eukaryotes and might cause or contribute to the aging of tissues that proliferate (Campisi, 2003). Cellular senescence appears to be caused by the progressive shortening of telomeres, which occurs with each cell division (Bodnar et al, 1998).…”

Section: Cellular Senescencementioning

confidence: 99%

Comparative aspects of zebrafish (Danio rerio) as a model for aging research

Gerhard

2003

Experimental Gerontology

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Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes

Cited by 190 publications

References 71 publications

Hsp90 mediates insulin‐like growth factor 1 and interleukin‐1β signaling in an age‐dependent manner in equine articular chondrocytes

Hsp90 mediates insulin‐like growth factor 1 and interleukin‐1β signaling in an age‐dependent manner in equine articular chondrocytes

Aging, tumor suppression and cancer: high wire-act!

Comparative aspects of zebrafish (Danio rerio) as a model for aging research

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