Cancers and the concept of cell senescence

BACKGROUND: Cancer incidence and mortality increase with age through much of adulthood, but earlier work has found that these rates decline among the very elderly. To compare incidence and mortality at the oldest ages, the authors investigated both in the same large population, which comprised 9.5% of the United States in 2000. The authors also report age-specific prevalence among the elderly, which has received little attention. METHODS: Twentythree cancer types were studied in men, and 24 cancer types were studied in women. Patient records were obtained from the SEER 9 cancer registries, and population figures were taken from the 2000 US Census. The authors explored the reliability of census data on the oldest old, which has been questioned. RESULTS: Age-specific incidence, prevalence, and mortality results are presented for the years 1998 to 2002. Incidence and mortality usually decreased or plateaued at very old ages. Prevalence usually decreased swiftly at ages >90 years. When there was statistical power, incidence normally peaked between ages 75 years and 90 years, dropping abruptly afterward. With several large exceptions, peak incidence and mortality coincided within AE5 years. Both rates often trended toward zero among centenarians, who may be asymptomatic or insusceptible. CONCLUSIONS: The current results were found to be consistent with autopsy and survival studies. Most age-specific models of carcinogenesis are based on cancer rate data for ages <85 years. The authors argue that these models could not fit the current results without fundamental modification and outline biologic mechanisms for such modification, mostly cellular and tissue senescence. They also recommend caution to researchers who use census data on the very elderly. Cancer 2012;118:1371-

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“…First, as we age, increasing arteriosclerosis limits local angiogenesis, perhaps sufficiently impeding the growth of tumors 45…”

Section: Discussionmentioning

confidence: 99%

Peak and decline in cancer incidence, mortality, and prevalence at old ages

Harding

Pompei

Wilson

2011

Cancer

104

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“…[25][26][27] Reasons for the subsequent decline in risk beyond those ages are unclear [28][29][30] but may reflect lower genetic susceptibility or the consequences of the natural aging process that inhibit tumor growth. 27,[31][32][33][34] For example, one theory suggests that the remodeling of the immune system among the very old, including increases in certain T cells and natural killer cells, creates a hostile environment for cancer growth. 34 Cellular senescence may also play a role, although this process can both inhibit and promote carcinogenesis.…”

Section: Selected Findingsmentioning

confidence: 99%

“…34 Cellular senescence may also play a role, although this process can both inhibit and promote carcinogenesis. 27,31,33 In addition, autopsy studies often report undiagnosed cancer in this age group, and therefore lower incidence rates likely reflect undetected cancer to some extent because of the less intensive use of diagnostic testing and screening. 35 Notably, however, incidence rates continue increasing through age 95 years and older for some cancers, including those of the colorectum, pancreas, stomach, and urinary bladder, as well as leukemia and skin melanoma.…”

Section: Selected Findingsmentioning

confidence: 99%

Cancer statistics for adults aged 85 years and older, 2019

DeSantis

Miller

Dale

et al. 2019

CA A Cancer J Clinicians

297

199

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Adults aged 85 years and older, the “oldest old,” are the fastest‐growing age group in the United States, yet relatively little is known about their cancer burden. Combining data from the National Cancer Institute, the North American Association of Central Cancer Registries, and the National Center for Health Statistics, the authors provide comprehensive information on cancer occurrence in adults aged 85 years and older. In 2019, there will be approximately 140,690 cancer cases diagnosed and 103,250 cancer deaths among the oldest old in the United States. The most common cancers in these individuals (lung, breast, prostate, and colorectum) are the same as those in the general population. Overall cancer incidence rates peaked in the oldest men and women around 1990 and have subsequently declined, with the pace accelerating during the past decade. These trends largely reflect declines in cancers of the prostate and colorectum and, more recently, cancers of the lung among men and the breast among women. We note differences in trends for some cancers in the oldest age group (eg, lung cancer and melanoma) compared with adults aged 65 to 84 years, which reflect elevated risks in the oldest generations. In addition, cancers in the oldest old are often more advanced at diagnosis. For example, breast and colorectal cancers diagnosed in patients aged 85 years and older are about 10% less likely to be diagnosed at a local stage compared with those diagnosed in patients aged 65 to 84 years. Patients with cancer who are aged 85 years and older have the lowest relative survival of any age group, with the largest disparities noted when cancer is diagnosed at advanced stages. They are also less likely to receive surgical treatment for their cancers; only 65% of breast cancer patients aged 85 years and older received surgery compared with 89% of those aged 65 to 84 years. This difference may reflect the complexities of treating older patients, including the presence of multiple comorbidities, functional declines, and cognitive impairment, as well as competing mortality risks and undertreatment. More research on cancer in the oldest Americans is needed to improve outcomes and anticipate the complex health care needs of this rapidly growing population.

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“…However, at least two groups did not find a correlation (Goldstein et al 1978;Cristofalo et al 1998). It should be stressed that this parameter is difficult to ascertain since there are different fibroblast populations differing in growth potential, which is related to the developmental characteristics of each organ and tissue (Macieira-Coelho 2003). Indeed, the paper from Cristofalo's group suggests that the cell populations studied from older donors come from tissues containing a mosaic of cells each having different population doubling potential.…”

mentioning

confidence: 99%

“…These kinetics of cell proliferation end up with a post-mitotic state with a particular morphology, which has been denominated phase IV (Macieira-Coelho and Taboury 1982) in addition to the phases I, II and III described by Hayflick and Moorhead (1961). There are other parameters that render the detection of a correlation difficult, they concern the physiopathology of the donor; certain conditions decrease and others increase the division potential (Macieira-Coelho 2003).…”

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confidence: 99%

Cell division and aging of the organism

Macieira‐Coelho

2011

Biogerontology

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The capacity to regenerate cell compartments through cell proliferation is an important characteristic of many developed metazoan tissues. Pre- and post-natal development proceeds through the modifications occurring during cell division. Experiments with cultivated cells showed that cell proliferation originates changes in cell functions and coordinations that contribute to aging and senescence. The implications of the finite cell proliferation to aging of the organism is not the accumulation of cells at the end of their life cycle, but rather the drift in cell function created by cell division. Comparative gerontology shows that the regulation of the length of telomeres has no implications for aging. On the other hand there are interspecies differences in regard to the somatic cell division potential that seem to be related with the "plasticity" of the genome and with longevity, which should be viewed independently of the aging phenomenon. Telomeres may play a role in this plasticity through the regulation of chromosome recombination, and via the latter also in development.

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Cancers and the concept of cell senescence

Cited by 12 publications

References 137 publications

Peak and decline in cancer incidence, mortality, and prevalence at old ages

Peak and decline in cancer incidence, mortality, and prevalence at old ages

Cancer statistics for adults aged 85 years and older, 2019

Cell division and aging of the organism

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