Calorie Restriction and Fasting Benefit the Aging Heart
The practice of calorie restriction, intermittent fasting, and related strategies such the fasting mimicking diet are thought to produce benefits largely through increased or more efficient operation of the cellular maintenance process of autophagy. The various forms of autophagy work to remove damaged molecules and structures in the cell, and better cell function maintained over time throughout the body is expected to result in slowed aging. Certainly a great many of the approaches shown to slow aging in short-lived species are characterized by improved autophagy, and influence the same regulatory systems that are triggered by a low calorie intake and consequent hunger.
Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins, damaged organelles, and excessive lipids within mammalian cells. A growing body of data indicates that autophagy is reduced in aging cells. This reduction leads to various diseases, such as myocardial hypertrophy, infarction, and atherosclerosis. Recent studies in animal models of an aging heart showed that fasting-induced autophagy improved cardiac function and longevity. This improvement is related to autophagic clearance of damaged cellular components via either bulk or selective autophagy (such as mitophagy).
Short-term caloric restriction (CR) for 10 weeks in mice rejuvenated symptoms of the aging heart, such as significant improvement in diastolic function and regression of age-dependent cardiac hypertrophy. Moreover, CR reversed age-dependent cardiac proteome remodeling and mitigated oxidative damage and ubiquitination in these mice. In aged animals, hypertrophy, and fibrosis, as well as systolic and diastolic dysfunctions, improved after CR. The beneficial effects of CR observed in cardiomyocytes include enhanced mitochondrial fitness and reduced oxidative stress, apoptotic cell death, inflammation, and importantly, senescence.
In vasculature, CR helps improve endothelial cell function and attenuates collagen deposition, elastin remodeling, and oxidative stress; as a result, CR reduces arterial stiffness. Another study revealed improvements in numerous markers of cardiovascular health in humans after short-term periodic fasting, which is also a pro-autophagic dietary regimen.
In conclusion, fasting-induced autophagy is beneficial for ensuring cardiac function, preventing disease, and improving longevity. However, additional studies in vivo in animal models of cardiac aging are needed to determine the specific molecular mechanisms involved in normalizing autophagy by fasting. In addition, large-scale studies on humans are needed. Importantly, further in vitro research should be directed toward human cardiac tissues to better understand the molecular mechanisms of fasting-induced autophagy and its beneficial effects on longevity pathways and prevention of cardiovascular disease.