Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy.

Abstract

To determine the effects of aging on the human myocardium, 67 O ne of the major difficulties encountered in the study of the effects of age on the cardiovascular system is the differentiation of the aging process itself from the presence of specific disease states. Atherosclerosis, diabetes, and ischemic heart disease are common events in humans, and the severity of these pathological conditions increases with age. Because the contribution of these variables to the alterations of the aged myocardium cannot easily be separated from the aging phenomenon alone, the changes of the heart throughout life are therefore the result of multifactorial events in which aging plays an important but indistinguishable role.1 There is no temporal reference point that can be used to distinguish between maturational changes beyond sexual maturity and the aging changes per se, since they are both controlled by time as a critical factor.'-3 Thus, the issue of whether aging of the heart has to be regarded as a successful adaptation or as a progressive disease state remains a matter of controversy, with data being accumulated in support of the former1-4 and the latter.5-9 However, it is well established that in both humans and animals myocyte proliferation occurs shortly after birth'0-13 and that the growth of the heart, during the relatively early phases of postnatal life and long before sexual maturity is reached, is controlled by hypertrophy of myocytesl213 and hyperplasia of capillary endothelial cells and interstitial fibroblasts.13 Although DNA synthesis with ploidy formation in adult human cardiac myocytes has been described,14-17 this phenomenon does not alter the number of muscle cells and/or muscle cell nuclei in the tissue, so that the total number of myocytes or myocyte nuclei in the ventricle can be used as an absolute reference parameter for the evaluation of the effects of aging on the myocardium. This approach was used in the present investigation to determine whether myocyte cell loss accompanies the life span of humans and may constitute the underlying cause for the occurrence of congestive heart failure in the elderly. Materials and Methods Study Design and Selection CriteriaSixty-seven human hearts were collected from a total number of 1,176 autopsies performed at the University Hospital of Parma Medical School during 1988 and 1989. All 67 hearts were collected within 24 hours after death. These cases were assumed to represent normal aging according to preautopsy criteria, autopsy criteria, and histological criteria, which are listed below.Preautopsy criteria for inclusion in the study. These criteria were as follows: 1) sudden death associated

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

“…Some collagen family members were also up-regulated, including Type XV collagen alpha 1, Type VI collagen alpha 3, Type IV collagen alpha 1, and Type VI collagen alpha 2. These observations are consistent with previous findings that the aging heart undergoes ECM protein deposition (30), fibrosis (31), and cardiomyocyte hypertrophy (11).…”

“…Age-related changes in human and rodent hearts include a reduction in the number of myocytes (10,11), myocyte hypertrophy (11,12), cardiac fibrosis (13), lipofuscin pigment accumulation (14), a reduction in calcium transport across sarcoplasmic reticulum membrane (15), and alterations in the response to ␤-adrenergic stimulation (16). Collectively, these alterations likely contribute to age-related heart diseases being the leading cause of mortality in the U.S. (17).…”

Myocyte Death in Streptozotocin-Induced Diabetes in Rats Is Angiotensin II- Dependent

“…Both phenomena decrease the reserve of the myocardium to sustain increases in mechanical load generated by myocardial infarction, systemic hypertension, or their combination. Diabetic cardiomyopathy resembles the aged heart in men, in which tissue damage is not apparent in spite of an agedependent loss of myocytes and reactive hypertrophy of the viable cells (Olivetti et al, 1991(Olivetti et al, , 1995. Similar findings have been obtained in aging Sprague-Dawley rats (Anversa et al, 1986).…”

Comparative cardiovascular physiology and pathology in selected lineages of minipigs

“…20 Standard published human ECG results consist of an HR of 60-100 beats/min, a mean PR interval of 120-200 ms, a mean QRS interval of <120 ms, and a mean QT interval of 420 ms. 21,22 In an earlier National Health Statistics Report, the mean weight of female adults over 20 years of age in the United States from 2003 to 2006 was 74.7 kg and that of males was 88.3 kg. 23 Additionally, a study evaluating the diseasefree aging heart reported BW from adults over 20 years of age ranging from 51 to 99 kg and HW of 123 to 306 g. 24 …”