The strongest risk factor for most types of cancer is aging. Numerous aging-dependent genetic and epigenetic events as well as metabolic alterations are likely to be major contributors to increased cancer susceptibility in old age promoting a pro-tumorigenic tissue microenvironment. Epigenetic-mediated changes in response to dietary and other environmental triggers throughout the course of life dictate epigenetic " signatures " that alter metabolic pathways linking the process of aging with cancer risk. A wide spectrum of multiple age-related epigenetic " hits ", from promoter hypermethylation, histone deacetylation and gene silencing to impaired NF-κ B signaling with up-regulation of cytokines and chronic inflammation, may account for predisposition to age-associated malignancies such as colon, breast (postmenopausal) and prostate cancer. The cancer-prone phenotype of old age is associated with insulin resistance and its related metabolic syndrome which elicits many of the signs of early agng. In fact, longevity studies have often implicated genes that regulate lifespan through insulin or insulin-like signaling pathways. Interestingly, a family of epigenetic enzymes with histone deacetylase (HDAC) activity, known as sirtuins, are involved in the extension of lifespan mediated by caloric restriction (CR) regulating gene expression, DNA repair, insulin sensitivity, NF-κ B signaling and apoptosis. CR exerts protective effects on carcinogenesis by maintaining an insulin-sensitive phenotype characterized by lifelong maintenance of optimal levels of key fat-derived cytokines (lipokines). Mechanistic studies with models of CR or with " CR-mimetics " may provide insight on how the aging-related insulin resistance and subsequent chronic inflammation might modulate epigenetic processes that affect age-associated diseases such as the development and progression of cancer. A greater understanding of the interrelations among diet, aging, insulin resistance, inflammation and cancer at the epigenetic level of regulation will help us design new dietary/pharmacological preventive strategies specifically targeting key epigenetic signaling networks.
|Original language||English (US)|
|Title of host publication||Epigenetics and Human Health|
|Subtitle of host publication||Linking Hereditary, Environmental and Nutritional Aspects|
|Number of pages||16|
|Publication status||Published - Jan 8 2010|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)