Pharmacological Strategies to Retard Cardiovascular Aging

Abstract

Aging is the major risk factor for cardiovascular diseases, which are the leading cause of death in the United States. Traditionally, the effort to prevent cardiovascular disease has been focused on addressing the conventional risk factors, including hypertension, hyperglycemia, hypercholesterolemia, and high circulating levels of triglycerides. However, recent preclinical studies have identified new approaches to combat cardiovascular disease. Calorie restriction has been reproducibly shown to prolong lifespan in various experimental model animals. This has led to the development of calorie restriction mimetics and other pharmacological interventions capable to delay age-related diseases. In this review, we will address the mechanistic effects of aging per se on the cardiovascular system and focus on the prolongevity benefits of various therapeutic strategies that support cardiovascular health.

Keywords: aging; calorie restriction; cardiovascular diseases; pharmacological strategies; prevention.

FIGURE 1. Pharmacological strategies to combat cardiovascular aging

Age-associated changes in cardiac and vascular properties (depicted in the inner red circle) can be delayed by targeting the related pathways (in the middle yellow circle) with small molecules (represented in the outer blue circle). Some of the pharmacological strategies highlighted in the diagram (bold and underlined) have been shown to improve longevity in healthy mammals. AMPK, 5’ adenosine monophosphate-activated protein kinase; Ang-II, angiotensin II; AT1, angiotensin II receptor, type 1; Chol, cholesterol; GH, growth hormone; iACE, inhibitors of angiotensin-converting enzyme; IGF-1, insulin-like growth factor-1; mTOR, mechanistic target of rapamycin; NO, nitric oxide; NOS, nitric oxide synthase; Nrf2, NF-E2-related factor 2; PARP-1, poly (ADP-ribose) polymerase 1; PUFAs, polyunsaturated fatty acids; ROS, reactive oxygen species; SIRT-1, sirtuin (silent mating type information regulation 2 homolog) 1.

FIGURE 2. Anti-aging effects of caloric restriction in the cardiovascular system

The up-arrow notation indicates an improvement or increase while the down-arrow shows decrease or impairment of cardiovascular functions and pathologies. NO, nitric oxide.