最先端研究セミナー

 

講演者：　南野　徹　（新潟大学大学院医歯薬総合研究科　循環器内科  教授）

演題：　Role of Cellular Aging in Cardio-metabolic 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. An important feature shared by several types of senescent cells is persistent up-regulation of inflammatory molecules and accumulating evidence has suggested a critical role of senescence-induced inflammation in metabolic and cardiovascular disease. Here I will present our recent data on the role of cellular senescence in age-related pathologies and will discuss the potential of anti-senescence as a novel therapeutic strategy for age-associated diseases.

 

Reference:

1. Shimizu I, Yoshida Y, Suda M, Minamino T. DNA damage response and metabolic disease. Cell Metab 2014; 20: 967-977.
2. Minamino T and Komuro I. Vascular aging: insights from studies on cellular senescence, stem cell aging, and progeroid syndromes. Nat Rev Cardiol 2008; 5: 637-648.
3. Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T, Nojima A, Nabetani A, Oike Y, Matsubara H, Ishikawa F, Komuro I. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med 2009; 15: 1082-1087.
4. Minamino T, Sano M, and Komuro I et al. p53-induced Inhibition of Hif-1 Causes Cardiac Dysfunction during Pressure Overload. Nature 2007 446: 444-448.

 

担当分野：　腎臓内科学　向山（内線：5164）

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