The number of p16INK4a positive cells in human skin reflects biological age

Waaijer, M.E.C.; Parish, W. E.; Strongitharm, Barbara H.; Heemst, Diana van; Slagboom, P. Eline; Craen, Anton J. M. de; Sedivy, John M.; Westendorp, Rudi G. J.; Gunn, David A.; Maier, Andrea B.

doi:10.1111/j.1474-9726.2012.00837.x

Cited by 229 publications

(213 citation statements)

References 24 publications

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“…In contrast to nevus melanocytes, these cells always appeared to lack expression of proliferation-promoting Wnt target genes. Significantly, previous studies have identified similarly positioned p16-expressing cells in the epidermis, morphologically resembling melanocytes, whose abundance increases with age (53,54). The trigger of p16 expression in these epidermal melanocytes, be it age-associated acquisition of an activated oncogene or another mode of stress, and the relationship, if any, of these cells to melanoma remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Wnt signaling potentiates nevogenesis

Pawlikowski

McBryan

Tuyn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway (senescence-associated secretory phenotype). Cellular senescence is also a tumor suppressor mechanism, to which both proliferation arrest and senescence-associated secretory phenotype are thought to contribute. The melanocytes within benign human nevi are a paradigm for tumor-suppressive senescent cells in a premalignant neoplasm. Here a comparison of proliferating and senescent melanocytes and melanoma cell lines by RNA sequencing emphasizes the importance of senescenceassociated proliferation arrest in suppression of transformation. Previous studies showed that activation of the Wnt signaling pathway can delay or bypass senescence. Consistent with this, we present evidence that repression of Wnt signaling contributes to melanocyte senescence in vitro. Surprisingly, Wnt signaling is active in many senescent human melanocytes in nevi, and this is linked to histological indicators of higher proliferative and malignant potential. In a mouse, activated Wnt signaling delays senescenceassociated proliferation arrest to expand the population of senescent oncogene-expressing melanocytes. These results suggest that Wnt signaling can potentiate nevogenesis in vivo by delaying senescence. Further, we suggest that activated Wnt signaling in human nevi undermines senescence-mediated tumor suppression and enhances the probability of malignancy.

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Section: Discussionmentioning

confidence: 99%

Wnt signaling potentiates nevogenesis

Pawlikowski

McBryan

Tuyn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…There is now strong evidence that cellular senescence is a potent anticancer mechanism (39)(40)(41)(42). In contrast, despite its name, its discovery over 50 years ago, and increasing data associating senescent cells with aging phenotypes and age-related pathology (43)(44)(45)(46)(47)(48)(49)(50), evidence has only recently emerged showing that eliminating senescent cells can actually delay age-related dysfunction (51), at least in a progeroid mouse model. This finding still must be tested in chronologically aged models, but this is the first clear evidence that senescent cells are important drivers of multiple age-related pathologies.…”

Section: Cellular Senescencementioning

confidence: 99%

“…The abundance of senescent cells increases in multiple tissues with chronological aging and in progeroid syndromes (43,47,50,(52)(53)(54)(55). Several processes have been identified that cause or are associated with cellular senescence, all of which also increase with age ( Figure 3).…”

Section: Cellular Senescencementioning

confidence: 99%

Cellular senescence and the senescent secretory phenotype: therapeutic opportunities

Tchkonia¹,

Zhu²,

Deursen³

et al. 2013

J. Clin. Invest.

1,455

1,251

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Aging is the largest risk factor for most chronic diseases, which account for the majority of morbidity and health care expenditures in developed nations. New findings suggest that aging is a modifiable risk factor, and it may be feasible to delay age-related diseases as a group by modulating fundamental aging mechanisms. One such mechanism is cellular senescence, which can cause chronic inflammation through the senescence-associated secretory phenotype (SASP). We review the mechanisms that induce senescence and the SASP, their associations with chronic disease and frailty, therapeutic opportunities based on targeting senescent cells and the SASP, and potential paths to developing clinical interventions.

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“…(65) Cellular senescence, as one basic process that play most contribution to age-related dysfunction and chronic sterile inflammation, refers to the essentially irreversible growth arrest that occurs when cells experience potentially oncogenic insults (58,(130)(131)(132)(133)(134), and now believe that it was the potent anticancer mechanism (135)(136)(137)(138). In contrast, despite its name, its discovery over 50 years ago, and increasing data associating senescent cells with aging phenotypes and age-related pathology (59,(139)(140)(141)(142)(143)(144)(145), while eliminating senescent cells could delay age-related dysfunction (146), at least in a progeroid mouse model. Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) are clearly related to age and can reduced life span.…”

Section: Telomeres and Diseasesmentioning

confidence: 99%

Telomere in Aging and Age-Related Diseases

2017

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B ACKGROUND:The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span. CONTENT:Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic Abstract R E V I E W A R T I C L Einstability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases' pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications. SUMMARY:Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management.

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The number of p16INK4a positive cells in human skin reflects biological age

Cited by 229 publications

References 24 publications

Wnt signaling potentiates nevogenesis

Wnt signaling potentiates nevogenesis

Cellular senescence and the senescent secretory phenotype: therapeutic opportunities

Telomere in Aging and Age-Related Diseases

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