Heart Attack Risk is Age-Related, but Aging Also Makes Treatments Less Effective

Aging makes everything worse. Its mechanisms of damage and consequence degrade tissue function to the point of catastrophic failure, as in a heart attack. That same damage also makes the immediate consequence of a heart attack worse, and reduces regenerative capacity and the ability to respond to therapies. All in all degenerative aging is an unpleasant business, lacking an upside. The right way forward is to periodically repair the damage before it reaches a pathological level, rather than working on ways to mitigate the consequences of a sizable burden of damage.

Aging elevates the susceptibility of the heart to ischemia and myocardial infarction (MI): over 50% of ischemic heart diseases occur in people older than 70s. Cardiac contractility declines suddenly in post-ischemia infarction, which can induce heart failure and even cause death. The EF and FS drop significantly in response to cardiac stress in advanced age, which is implicated by the progressive degeneration and reduction in cardiac myocytes. Beside changes in cellular level, a number of molecular alternation contribute to age related stress intolerance, including Ca2+ handling impairment, mitochondrial dysfunction, free radical accumulation, and alteration of myosin protein expression. Recently, the crucial role of epigenetic alteration in the cardiac aging process has attracted much attention.

The therapeutic effect of ischemic cardiac dysfunction varies in old patients. Patients older than 80 have worse survival rate than 70-year-old patients after cardiac ischemic therapy, but the survival rate for patients who undergo coronary artery bypass grafting is not affected by age. Early intervention for aging patients with ischemic heart disease will decrease the mortality rate. The difference in therapeutic effects between the aged and young groups also existed following cell therapies. Aged mice with cardiac injuries that underwent cardiosphere-derived cell (CDCs) transplantation showed no improvement in cardiac function, while cardiac function was improved in the young.

Furthermore, the results of cardiac regeneration therapy for aging people is still in a matter of debate. The effectiveness of stem cell therapies is always influenced by aging-related environmental changes. For example, ageing-induced low grade systematic inflammation cause poor survival rate of injected stem cells. Similarly, stem cell-derived exosome therapies are also largely limited by recipient cell senescence which causes a deteriorated cell proliferation ability and a weaken cardiac myocyte performance.

Link: https://doi.org/10.14336/AD.2019.0522

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