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Aging, Cancer and Apoptosis in Animal Models and Clinical Settings

  • Masanobu Kitagawa
  • Katsuiku Hirokawa

The incidence of cancer generally increases with aging of hosts in both animals and humans [39, 49], and thus advanced age is, so to say, a most powerful and potent carcinogen. In humans, the overall incidence of cancer rises exponentially in the 6th, 7th and 8th decades of life [45]. Although it is not clear what underlies this close link between cancer and advanced age, it is believed that the cancer-prone phenotype of aged people is due to the cumulative mutational load over a person’s lifetime. In other words, the high frequency of cancer in older individuals simply reflects a more prolonged exposure to various carcinogenic events [12]. Analysis of the frequency of human cancer as a function of age shows that between 4 and 7 mutations in key genes are usually necessary to produce cancers. However, it is still under debate whether normal mutation rates followed by the selective advantage of mutated clones are enough to produce the numerous mutations found in human cancers [106]. But, by whatever means, cancers might be caused by genetic/epigenetic alterations. Even under physiological conditions, the stem cells of our body may contain multiple somatic mutations, some of which target cancer-relevant genes [113]. For example, 1% of neonatal blood samples contain significant numbers of myeloid clones harboring oncogenic fusion of chromosomes [90] and 1/3 of adults possess detectable IgH-BCL2 translocations associated with follicular lymphoma [85]. Thus, our body’s cells experience multiple routes for oncogenesis every day. However, not so many people are affected by cancer. This may be partly because we have adequate systems that suppress carcinogenesis and constrain the growth and survival of potential cancer cells. In humans, tumor suppressor systems include the p16-Rb, ARF-p53 and telomere systems. Some of these systems protect the genome from damage or mutation. Others eliminate or arrest the proliferation of potential cancer cells by processes called apoptosis or cellular senescence. The Rb system induces cell cycle arrest and p53 and telomere dysfunction, which in turn induce apoptosis in abnormal cells. Furthermore, the immune system influences various aspects of tumor growth and metastasis [48], although there is no conclusive evidence of an immune surveillance system for carcinogenesis in humans [38].

Aging Carcinogenesis Apoptosis Epigenetic change DNA damage 

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Masanobu Kitagawa
    • 1
  • Katsuiku Hirokawa
    • 1
  1. 1.Department of Comprehensive Pathology Aging and Developmental Sciences Graduate SchoolTokyo Medical and Dental UniversityBunkyo-ku, TokyoJapan

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