Considerable differences were found in the incidence of age-associated diseases and the mean lifespan between countries of similar social background. Previously, the inhibition of age-associated disease progression was considered to be attributable to anti-oxidants in foods, such as isoflavones and resveratrol. However, the results of recent studies do not support the role of anti-oxidants in the inhibition of age-associated diseases and senescence. We have reported that healthy foods such as beans, mushrooms, seafoods and vegetables, and healthy dietary traditions such as the Mediterranean diet and Japanese foods are rich in polyamines (spermine and spermidine). Polyamines are synthesized in rapidly growing cells; however, this ability decreases with aging. In addition to de novo synthesis, cells can take up polyamines from their surroundings. An important source of whole body polyamines originates in the intestinal lumen, e.g., food-derived polyamines. Polyamines in the intestinal lumen are absorbed quickly, and continuously increased polyamine intake elevates blood polyamine levels in humans and mice. In addition to the many biological activities that help protect cells and tissues from harmful stimuli, we have shown that polyamines suppress pro-inflammatory status, characterized by the suppression of leukocyte function associate antigen 1 (LFA-1) expression and pro-inflammatory cytokine production. Moreover, increased intracellular spermine from extra-cellular sources enhanced the activities of DNA methyltransferases (DNMT) and suppressed polyamine deficiency-induced genome-wide demethylation/methylation in vitro. Long-term increased polyamine intake inhibited age-associated pathological changes and suppressed abnormal genome-wide demethylation/methylation in Jc1 : ICR male mice. In addition, increased polyamine intake was associated with a decreased incidence of colon tumors in BALB/c mice after 1,2-demethylhydrazine administration. Aging is associated with decreased polyamine synthesis, enhanced pro-inflammatory status (e.g., increased LFA-1 expression), decreased DNMT activities, and enhanced genome-wide demethylation/methylation; therefore, dietary polyamine represents a valuable food element to suppress age-associated pathologies and extend the lifespan of humans.