Molecular mechanisms of cardiac aging

Age-associated changes in cardiovascular structure/ function are implicated in the markedly increased risk for cardiovascular disease in older persons. Aging not only prolongs exposure to several other cardiovascular risks, but also leads to intrinsic cardiac changes, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, includ- ing left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenu- ated in mice overexpressing catalase targeted to mitochondria （mCAT）. These findings demonstrate the critical role of rnitochondrial reactive oxygen species （ROS） in cardiac ag ing and support the potential antioxidants to cardiac aging lar diseases. application of mitochondrial and age-related cardiovascular diseases.

Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

Presenilin and Alzheimer’s disease interactions with aging,exercise and high-fat diet:A systematic review

Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases seriously affect the quality of life and longevity of the population and place a huge burden on health care and economic systems around the world.Humans have two types of Psn,presenilin-1(PSEN1)and presenilin-2(PSEN2).Mutations in the genes encoding PSEN1,PSEN2,and amyloid precursor protein(APP)have been identified as the major genetic causes of AD.Psn is a complex gene strongly influenced by genetic and environmental factors.The effects of exercise,training,and a high-fat diet on the Psn gene expressed in the heart and its related pathways are not fully understood.Fortunately,relevant aspects of the mutational effects on Psn can be studied experimentally in easily handled animal models,including Drosophila,mice,and other animals,all of which share orthologous genes of Psn with humans.Many previous studies have linked aging,exercise training,and a high-fat diet to the Psn gene.This review discusses the interrelationship between aging,exercise training,and a high-fat diet on the Psn gene and its associated disease,AD.The aim is to understand the adverse effects of Psn gene mutations on the body and the diseases caused by AD,find ways to alleviate the adverse effects and provide new directions for the improvement of treatment strategies for diseases caused by Psn gene mutations.