The various heat shock proteins play a role in the hormetic response to damage. When damaged, cells dial up their repair activities for a while, and if the damage is mild and brief, the result is a net gain in quality control. Less damage means less dysfunction, and this is why increased cellular maintenance activities are involved in many of the methods demonstrated to modestly slow aging in animal studies. It is possible to dial up maintenance without using damage as a trigger, through suitable changes to levels of proteins, such as genetic engineering to increase the production of heat shock proteins:
Intrinsic cardiac aging is defined as slowly progressive functional declines and structural changes with age, in the absence of major cardiovascular risks such as hypertension, diabetes, hypercholesterolemia, and smoking. However, intrinsic cardiac aging can increase the vulnerability of the heart to both endogenous and exogenous stressors, ultimately increasing cardiovascular mortality and morbidity in elderly individuals. Therefore, interventions to combat cardiac aging not only will improve the healthspan of the elderly, but also can extend their lifespan by delaying cardiovascular disease-related deaths. Studies indicate that the pathogenesis of cardiac aging involves multiple molecular mechanisms, including oxidative stress, impaired autophagy, metabolic changes, dysregulated calcium homeostasis, and activation of neurohormonal signaling. Indeed, the reactive oxygen species (ROS) content significantly increases in the aged heart, while mitochondrial overexpression of catalase (an important antioxidative enzyme) improves the aging-induced decline in cardiac function and prolongs the lifespan of mice. Intracellular ROS in the aged heart are mainly generated from damaged mitochondria. In normal conditions, damaged mitochondria are selectively degraded through autophagy, a process known as mitophagy. Unfortunately, autophagy is progressively impaired over time.
Heat shock protein 27 (HSP27) is an ubiquitously expressed member of the small heat shock protein subfamily. Studies demonstrated the involvement of HSP27 in various biological functions, including the responses to oxidative stress, heat shock, and hypoxic/ischemia injury. Of particular interest to this study, we and others showed that overexpression of HSP27 protects cardiac function against cardiac injuries induced by ischemia/reperfusion, myocardial infarction, inflammation, and doxorubicin. The mechanisms that contribute to cardioprotection by HSP27 involve the antioxidative capacity, suppression of inflammatory responses, improvement of cardiomyocyte survival, and activation of autophagy and mitochondrial activity. It is possible, therefore, that overexpression of HSP27 protects the heart from aging-induced injury.
In this study, we examined the effects of HSP27 on cardiac aging using transgenic (Tg) mice with cardiac-specific expression of HSP27. We observed an improvement in cardiac function and decreases in the levels of cardiac aging markers in old Tg mice compared with age-matched wild-type (WT) controls. This action of HSP27 involves the antioxidative capacity and activation of mitochondrial autophagy (mitophagy). Our results suggest that management of HSP27 expression may serve as an alternative intervention to alleviate cardiac aging.