Age per se, confers the major risk for cardiovascular (CV) disease because specific pathophysiological mechanisms that underlie these diseases become superimposed on cardiac and vascular substrates that have been modified by an "aging process". In healthy humans, rigorously screened to exclude CV disease, non-human primates (NHP) and rodents, the large elastic arteries become dilated and stiffen and the intima thickens, and exhibits cell and sub-cellular features that resemble those that occur during vascular injury. Age-associated changes in human cardiac structure (Left Ventricular (LV) myocyte size and wall thicken, increase and myocyte number is reduced) and resting function( reduced early diastolic filling) occur, in part, in response to aging of the arterial system. CV reserve function in older humans without CV disease is limited by suboptimal ventricular-vascular coupling, due to an age associated augmentation vascular afterload, and reduced myocardial contractility, due, in part, to a diminished effectiveness to beta-adrenergic modulation. Cardiac myocytes of older rodents are characterized by increased size, altered membrane composition, altered calcium regulation, reduced Ca2+ tolerance and increased reactive O2 species levels in response to a variety of stressors.
Therapies to prevent or delay these CV changes that accompany aging reduces the risk for age-associated CV functional decline and the risk for disease. Evidence to indicate that diet, exercise habits, pharmacologic agents , e.g., those that interfere with Angiotensin II action, or novel collagen cross-link breakers, or gene therapy, can retard age associated changes in CV structure/function (1,2) will be presented.
Lakatta EG, Levy D. Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises.
Part I: Aging Arteries: A "Set Up" for Vascular Disease. Circulation: New Frontiers 2003;107:139-46.
Part II: The Aging Heart in Health: Links to Heart Disease. Circulation: New Frontiers 2003;107:346-54.
Lakatta EG. Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises.
Part III: Cellular and Molecular Clues to Heart and Arterial Aging. Circulation: New Frontiers 2003;107:490-7.