Article Page
Aging and Cardiovascular Disease: Exercise to the Rescue!
By Robert Christner, MS and Len Kravitz, PhD

According to Bouzid et al. (2015), “Aging is an intricate phenomenon characterized by a progressive decline in physiological functions and an increase in mortality, which is often accompanied by many pathological diseases.” Our species is long-lived compared to other primates. Pringle (2015) states that chimpanzees have a life expectancy of about 13 years compared to 78.5 yrs for U.S. babies born in 2009. Pringle explains that our lifespan is significantly longer due to medical advances with vaccines, antibiotics, sanitation, the availability of nutritious vegetables and fruits year-round, and our acquired ability to fight off many pathogens and irritants in the environment. A current line of concentrated investigation with some researchers, and the topic of this column, is determining ways to slow down the major effects of aging on the cardiovascular system in hopes for attaining longer lives.

How are Cardiovascular Disease, Oxidative Stress, and Inflammation related to Aging?
According to the WHO (2016), cardiovascular disease (CVD) is the number one cause of death in the world, accountable for 31% of all global deaths. It is caused by disorders of the heart and blood vessels, and includes heart attacks (coronary heart disease), stroke (cerebrovascular disease), elevated blood pressure, peripheral artery disease, rheumatic heart disease, congenital heart disease and heart failure (WHO, 2016). Advancing age is a major risk factor for CVD (Seals, Jablonski, and Donato 2011). Gliemann and colleagues (2016) explain that aging leads to the development of large artery thickening and stiffness. This stiffening is due to changes occurring within the artery wall. The resultant diminished cardiovascular function is due to a disorder known as endothelial dysfunction (Gliemann, Nyberg and Hellsten). Endothelium is a thin layer of cells that line the blood vessels. The endothelium is centrally involved with the regulation of vascular tone. Vascular tone refers to an optimal balance for blood vessels to perform vasoconstriction (narrowing of blood vessels) and vasodilation (widening of blood vessels) as needed for life sustaining processes. Endothelial dysfunction is characterized by a reduction, or impairment in the production of vasodilators, particularly nitric oxide (Seals, Jablonski, and Donato 2011). This means that people with endothelial dysfunction have blood vessels with a decreased capacity to dilate in response to certain stimuli. This imbalance is a key early step in the development of atherosclerosis (plaque buildup in the arteries).

Gliemann and colleagues (2016) note that atherosclerosis is accompanied by oxidative stress. The researchers explain that with aging, and the development of atherosclerotic plaque, there is an increased formation of harmful reactive oxygen species (ROS) in the endothelium coupled with a reduction in the body's ability to make more antioxidants to neutralize the ROS. This is referred to as oxidative stress; the body is unable to detoxify the harmful effects of the ROS.

Oxidative stress and endothelium dysfunction lead to a chronic, low-grade, detrimental inflammation (i.e., an imbalance of pro-inflammatory chemicals and not enough anti-inflammatory substances) in the vascular system. Chronic inflammation is associated with increased risk for disease, poor physical functioning and mortality (Woods et al., 2012).

Exercise: The BEST Line of Offense and Defense
Gliemann and colleagues (2016) summarize that cardiorespiratory exercise has a major effect on vascular endothelial function by improving factors such as the vasodilator-to-vasoconstrictor balance, reductions in inflammation and oxidative stress, and growth of new capillaries in skeletal muscle. In regards to endothelial function, exercise has consistently been shown to greatly improve vascular structure and function (Gliemann, Nyberg and Hellsten, 2016). The impairments observed with nitric oxide in the endothelium are minimized and even reversed with aerobic exercise. Interestingly, scientists are now discovering the specialized molecular mechanisms and signaling pathways that elicit this beneficial outcome.

In regards to chronic inflammation, Woods et al. (2012) conclude that exercise-induced loss of adipose tissue is related to exercise training-induced reductions in serum markers of inflammation. The researchers continue that adipose tissue, especially visceral fat, produces pro-inflammatory proteins that contribute to systemic inflammation. The researchers highlight that cardiorespiratory exercise also increases muscle production of specialized cytokines, which are molecular messengers that regulate various inflammatory responses in order to control the body's response to disease and infection. Additionally, cardiorespiratory exercise increases vagal tone, which may lead to a decrease in systemic inflammation (Woods et al., 2012). Vagal tone is the resting state regulatory mechanism of the vagus nerve on most of the body's internal organ systems, such as the heart, lungs, eyes, glands and digestive tract.

Sidebar 1: Genetics and Aging
Our DNA is what makes each of us an individual, it codes for every function and molecular process in our bodies. While we cannot currently alter our genome, we do have the ability to control a number of factors that impact the expression of our genetic makeup. Having “good genes” clearly can impact on longevity, but identifying what those are remains a mystery. Having genetic predisposition to any particular disorder and adopting poor lifestyle choices (e.g., unhealthy diet, physical inactivity, tobacco use and harmful use of alcohol) which favor health disorders can dramatically reduce lifespan. Avoiding lifestyle choices that lead to metabolic disorders, cardiovascular disease, and carcinogen exposure, can have a very positive impact on genetic predisposition. Lifestyle choices like exercise can mediate the impact of several health conditions including obesity, hypertension, and type 2 diabetes.

Side Bar 2: Diet, Disease Prevention and Aging
One of the banes of modern society is the reliance on calorie dense highly processed fast foods. The known detriments of these diets are: obesity, metabolic disorders, diabetes, hyperlipidemia, hypertension, and an increased prevalence of cancer (Lopez-Otin et al. 2016). The role of diet in health and disease is reaching a new level of awareness, and can now be associated with diseases or assist in the prevention of disease (Lopez-Otin et al). One notable diet however has shown to healthful due to its anti-inflammatory characteristics; this is the Mediterranean diet (Lopez-Otin et al). The Mediterranean diet is inspired by the natural diets found in Greece, southern France, Italy and Spain. This diet relies on a high intake of olive oils, fish, grains and legumes high in natural fiber, fresh fruits, and vegetables, along with moderate amounts of dairy, meat and alcohol. Lopez-Otin et al. summarize that a “Mediterranean diet rich in fibers and complex carbohydrates may have sizeable anti-aging effects, especially when combined with regular physical activity.”

Final Thoughts
There is mounting evidence that exercise, and increases in physical activity, plays a pivotal role in combating disease, extending the life cycle, and increasing the overall quality of life. At the molecular level, aerobic exercise is capable of reducing oxidative stress and inflammatory response while improving vascular function and cardiovascular health. In a population-based cohort of 661,137 men and women (average age = 62ys) from the U.S. and Europe, Arem et al. (2015) conclude that meeting the minimum exercise guidelines (i.e., 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic activity weekly for substantial health benefits) provides a substantial benefit for postponing mortality and lowering the risk for adverse cardiac events. Keep Moving!

Robert Christner, MS, has master's degrees in biology and exercise science and is currently pursuing his PhD in exercise science at the University of New Mexico. His research interests are in metabolism and in exercise as a moderator of diseases and aging.

Len Kravitz, PhD, CSCS is the program coordinator of exercise science and a researcher at the University of New Mexico where he received the Outstanding Teacher of the Year award. In addition to being a 2016 inductee into the National Fitness Hall of Fame, Dr. Kravitz was awarded the 2006 Fitness Educator of the Year by the American Council on Exercise, and has received the prestigious Canadian Fitness Professional Lifetime Achievement Award.

Arem, H., Moore, S.C., Patel, A. et al. (2015). Leisure time physical activity and mortality: A detailed pooled analysis of the dose-response relationship. JAMA Internal Medicine, 175(6), 959-967.
Bouzid, M.A, Filaire, E., McCall, A., and Fabre, C. (2015). Radical oxygen species, exercise and aging: An update, Sports Medicine, DOI 10.1007/s40279-015-0348-1
Gliemann, L., Nyberg, M., and Hellsten, Y. (2016). Effects of exercise training and resveratrol on vascular health in aging, Free Radical Biology and Medicine, 98, 165-176.
Lopez-Otin, C., Galluzzi, L., Freije, J.M.P., Madeo, F., and Kroemer, G. (2016). Metabolic control of longevity, Cell, 166, 803-821.
Pringle, H. (2015). Long live the humans, Scientific American, 24, March, 4-11.
Seals, D.R., Jablonski, K.L., and Donato, A.J. (2011). Aging and vascular endothelial function in humans. Clinical Science (London, England_: 1979), 120(9), 357-375.
World Health Organization: Cardiovascular Diseases (CVDs)
Accessed November 15, 2016
Woods, J.A., Wilung, K.R., Martin, S.A., and Kistler, B.M. (2012). Exercise, inflammation and aging, Aging and Disease, 3(1), 130-140.