S-07-1: TARGETING SENESCENT CELLS AS A NOVEL THERAPEUTIC STRATEGY FOR AGE-ASSOCIATED DISEASE

Abstract

Epidemiological studies have shown that age is the dominant risk factor for lifestyle-related diseases. The incidence and the prevalence of diabetes, heart failure, coronary heart disease and hypertension increase with advancing age. However, the molecular mechanisms underlying the increased risk of such diseases that is conferred by aging remain unclear. Cellular senescence is originally described as the finite replicative lifespan of human somatic cells in culture. Cellular senescence is accompanied by a specific set of phenotypic changes in morphology and gene expression including negative regulators of the cell cycle such as p53. Primary cultured cells from patients with premature aging syndromes are known to have a shorter lifespan than cells from age-matched healthy persons. It is also reported that the number of senescent cells increases in various tissues with advancing age. Interestingly, such accumulation of senescent cells in aged animals is attenuated by caloric restriction that regulates the lifespan regulatory system and delays age-associate phenotypes. I therefore hypothesize that cellular senescence in vivo contributes to the pathogenesis of age-associated disease and have shown a critical role of cellular senescence in age-related pathologies. However, a direct inhibition of cellular aging signaling would lead to the increased incidence of cancer, so we need to develop anti-senescent therapy without cancer development. Here I will show our recent data on a novel strategy of anti-senescent therapy for age-associated disease by targeting cellular senescence (Seno-antigens, Seno-metabolites, SASP), which would not promote tumorigenesis.