REVIEW ARTICLE Relationships between cancer and aging: a multilevel approach Vladimir N. Anisimov Æ Ewa Sikora Æ Graham Pawelec Received: 6 October 2008 / Accepted: 16 December 2008 / Published online: 21 January 2009 Ó Springer Science+Business Media B.V. 2009 Abstract The incidence of cancer increases with age in humans and in laboratory animals alike. There are different patterns of age-related distribution of tumors in different organs and tissues. Aging may increase or decrease the susceptibility of various tissues to initi- ation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer in two ways: tissue accumu- lation of cells in late stages of carcinogenesis and alterations in internal homeostasis, in particular, alter- ations in immune and endocrine systems. Increased susceptibility to the effects of tumor promoters is found both in aged animals and aged humans, as predicted by the multistage model of carcinogenesis. Aging is associated with a number of events at the molecular, cellular and physiological levels that influence carci- nogenesis and subsequent cancer growth. An improved understanding of age-associated variables impacting on the tumor microenvironment, as well as the cancer cells themselves, will result in improved treatment modalities in geriatric oncology. Keywords Aging Á Carcinogenesis Introduction It is well documented that the incidence of malignant tumors increases progressively with age, both in animals and humans (Anisimov 1987; Dix and Cohen 1999; Parkin et al. 2001; Balducci and Ershler 2005). Three major hypotheses have been proposed to explain the association of cancer and age. The first hypothesis holds that this association is a conse- quence of the duration of carcinogenesis. In other words, the high prevalence of cancer in older individuals simply reflects a more prolonged expo- sure to carcinogens (Peto et al. 1985). The second hypothesis proposes that age-related progressive changes in the internal milieu of the organism may provide an increasingly favorable environment for the induction of new neoplasia and for the growth of already existent, but latent malignant cells (Anisimov 1983, 2003a, b, c; Miller 1991; Dilman 1994; Simpson 1993). These mechanisms may also include proliferative senescence, as the senescent cells lose their ability to undergo apoptosis and produce some V. N. Anisimov (&) Department of Carcinogenesis and Oncogerontology, N. N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 197758, Russia e-mail: aging@mail.ru E. Sikora NENCKI Institute of Experimental Biology, Warsaw, Poland e-mail: esik@nencki.gov.pl G. Pawelec Center for Medical Research, University of Tu ¨bingen Medical School, Tu ¨bingen, Germany e-mail: graham.pawelec@uni-tuebingen.de 123 Biogerontology (2009) 10:323–338 DOI 10.1007/s10522-008-9209-8