Effects of Caloric Restriction on Cardiovascular Aging in Non-human Primates and Humans
Section snippets
Heart disease and aging
Due in large part to a 20-year increase in average life span during the second half of the 20th century, the median age of the worldās population is increasing, and this trend is expected to continue worldwide, with the average life span rising another 10 years by 2050.7 In the United States, the proportion of the population over 65 years of age is projected to increase from 12.4% in 2000 to 19.6% in 2030.8 The number of persons over 65 years of age is expected to increase from approximately 35
Cardiovascular disease and obesity
The link between obesity and CVD has been established clearly. Left ventricular hypertrophy, hypertension, diastolic dysfunction, poor cardiac contractility, and dyslipidemia are recognized cardiovascular complications of obesity.10, 11 In the past. it was believed that poor cardiovascular health in adults was a long-term effect of increased body mass. Recent studies, however, show that even obese children are developing signs of heart disease.12, 13 Currently, nearly 20% of US children are
Cardiovascular disease and metabolic syndrome
Metabolic syndrome, an increasingly common human age-related disorder driven mainly by the rising prevalence of obesity,24 originally was recognized in 1988 as a multiplex risk for CVD. It includes components of insulin resistance, hyperinsulinemia, glucose intolerance, increased triglycerides, decreased high-density lipoprotein (HDL) cholesterol, and hypertension.25 More recent definitions include obesity, or specifically abdominal obesity, in the diagnostic criteria.26, 27, 28, 29, 30, 31
Caloric restriction
Caloric restriction (CR) offers a powerful way to explore the aging process, because it is the only environmental or lifestyle intervention that has repeatedly and strongly been shown to increase maximum life span and retard aging in laboratory rodents.49, 50, 51, 52 The ability of CR to increase life span extends to fish, spiders, and other animals. Dogs on CR show an increased healthy life span and average life span.53, 54 In most rodent CR studies, mice or rats are fed 50% to 70% as many
The rhesus monkey model of caloric restriction
The rhesus monkey (Macaca mulatta), an Old World primate of either Indian or Asian origin, is a commonly used and extensively characterized biomedical model. Because of their evolutionary proximity to people, data from this model are easily translatable to human medicine.55, 56, 57, 58 Similarities between rhesus monkeys and people extend to almost all aspects of anatomy, physiology, neurology, endocrinology, immunology, behavior, and aging processes.59, 60 Of particular importance, rhesus
CR in people
The efficacy of CR in nonhuman primates86 suggests that CR might be beneficial in people also. Epidemiological data additionally suggest an inverse relationship between caloric intake and aging in people.51, 87, 88 Further evidence in support of benefits from moderate CR in people derives from an unplanned observation from the Biosphere 2 experiment. In this project, eight individuals, four men and four women, lived in a completely enclosed environment that was meant to contain all necessary
Summary
CVD is a major public health concern in the United States, affecting approximately one in three adults and accounting for one of every 2.8 deaths. With the aging of the population and the increasing obesity epidemic, incidence and prevalence rates of CVD will continue to increase. CR is the only intervention shown to increase maximum lifespan and retard aging in laboratory rodents and nonhuman primates. There is also strong evidence that CR improves several components of the metabolic syndrome
Acknowledgments
The authors gratefully acknowledge the excellent technical assistance provided by S. Baum, J. Christensen, J. A. Adriansjach, C. E. Armstrong, and the Animal Care, Veterinary, and Pathology Staff of the WNPRC.
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This work was supported by grants P01 AG-11915 (National Institute on Aging) and P51 RR000167 (National Center for Research Resources [NCRR]). This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01 from NCRR.