473 ISSN 1745-509X 10.2217/AHE.13.46 © 2013 Future Medicine Ltd Aging Health (2013) 9 (5), 473–482 Increased cellular inflammation also tends to intensify with advanced aging. Both an increased number of inflammation-producing CV risk fac- tors (e.g., visceral obesity, hypertension [HTN] and diabetes) and prolonged duration of their harmful effects accumulate over time, and mani- fest in age-related physiological changes and dis- ease [3]. Furthermore, as chronic diseases emerge (e.g., coronary heart disease [CHD], arthritis and other inflammatory processes), they add to ambi- ent cellular inflammation. In combination with oxidative stress, the progressing inflammatory state not only induces more cellular and physi- ological injury, but it also promotes gene expres- sion patterns that are distinct with age, which essentially determine age-related vascular, cardiac and skeletal muscle morphological/physiological patterns that differ from younger adulthood. Phenotypic manifestations of age on vasculature, heart & skeletal muscle, & related physiological/clinical implications With advancing age, there is a progressive thick- ening of the intimal–medial wall layers in large and medium sized blood vessels. A complex aging biology has been described [4]; high oxidative stress and related increases in angiotensin II leads to progressive vascular fibrosis, increased collagen and calcium accumulation, covalent crosslinking of collagen, fragmentation of elastin and migra- tion of smooth muscle cells from the medial layer to the subintimal layer [5]. Predominant stiffening is typical. Among the physiological implications of age- related vascular stiffening, blood flow velocity, Life expectancy is increasing, and a burgeoning population of older adults has created new chal- lenges to our current healthcare system. Aging entails a constellation of cardiovascular (CV) effects (extending from subcellular to integrated organ system morphology/physiology) that determine age-related decrements in physical and cognitive function, as well as related sus- ceptibility to atherosclerosis and other chronic diseases that more easily overwhelm diminish- ing CV reserves. While these patterns are typi- cal, exercise training (ET) can positively alter the trajectory of typical aging effects, such that older adults who regularly engage in ET can be relatively more robust with morphology and function, which are comparatively more youth- ful. Basic components of cellular performance, as well as integrated dynamics of physiology and function, can be preserved/improved by ET, essentially counter balancing what are otherwise insidious age-related detriments. Formative elements of senescence & disease: oxidative stress & inflammation Oxidative stress results from cellular metabolism, and can be exacerbated by environmental and disease factors. While there are natural homeo- static capacities that normally moderate the inju- rious potential of oxidative stress, these protec- tive mechanisms diminish with advancing age [1]. Reactive oxygen species (ROS) typically accu- mulate with damaging effects on the vasculature, myocardium and skeletal muscle that erode physical function and increase susceptibility to disease [2]. Exercise: a vital means to moderate cardiovascular aging Karla Daniels 1 , Ross Arena 2 , Carl J Lavie 3,4 , Lawrence P Cahalin 5 & Daniel E Forman* 1,6 While aging is associated with predictable phenotypic changes, with associated effects on cardiovascular physiology and related clinical manifestations, the timing and pace of aging is modifiable. Exercise has been demonstrated to moderate fundamental aspects of aging and related vulnerability to disease. Habitual physical activity and exercise is associated with relatively more youthful physiology and capacities extending from subcellular function to integrated organ systems. Even when seniors are already encumbered by age-related limitations or disease, aerobic, strength and other training regimens can help restore physical function, balance and flexibility, as well as inter-related dynamics of health. In this perspective, we describe age-related changes and vulnerabilities, particularly pertaining to the cardiovascular system and inter-related skeletal muscle health, and the utility of exercise training to allay aging and/or restore capacities even after aging encumbrances have started. 1 Division of Cardiovascular Medicine, Brigham & Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA 2 Department of Physical Therapy, College of Applied Health Sciences, University of Illinois Chicago, Chicago, IL, USA 3 John Ochsner Heart & Vascular Institute, Ochsner Clinical School – The University of Queensland School of Medicine, New Orleans, LA, USA 4 Department of Preventive Medicine, Pennington Biomedical Research Center, Baton Rouge, LA, USA 5 Department of Physical Therapy, Leonard M Miller School of Medicine, University of Miami, Miami, FL, USA 6 New England Geriatric Research, Education & Clinical Center, VA Boston Healthcare System, Washington, DC, USA *Author for correspondence: Tel.: +1 857 307 1989 deforman@partners.org Keywords •฀aging • cardiorespiratory fitness • cardiovascular • diastole • exercise • myocardial compliance • physical activity • sarcopenia • vascular stiffness PERSPECTIVE part of For reprint orders, please contact: reprints@futuremedicine.com