Age Associated Changes In Structural And Functional Cardio-Vascular Properties

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

I. I. Patterns and Determinants of CV Aging: We have shown that serum levels of GDF-15 increase with age; are associated with a stiffer aorta; “mediate” a large proportion of the age-associated increase in arterial stiffness; pose risks because of their association with greater mortality; and are significantly associated with the variant rs11549407, which causes thalassemia major in homozygosity. Because of its consistent ability to predict functional and clinical outcomes, including all-cause mortality, we conclude that GDF-15 serum levels serve as a robust biomarker for the continuum from health to the emergence of clinical disease during aging and, subsequently, to the likelihood of mortality (Oppong, 2025). Aging per se is a major risk factor for cardiovascular diseases and is associated with progressive changes in cardiac structure and function. We performed a 2D echocardiographic study in non-human primates (NHP) to establish age- and sex-associated differences in cardiac function and morphometry in this animal model. The diameters of the cardiac chambers did not differ significantly by age group, but males had larger left ventricular diameters in diastole and in systole and left atrial diameter. Left ventricular mass/body surface area did not vary significantly with age and sex. Ejection fraction did not differ by age and females presented a higher ejection fraction than males. Diastolic function, defined by early to late mitral peak flow velocity ratio (E/A), was significantly lower in old rhesus monkeys and was lower in females compared to males. Right ventricular function did not differ by age or sex, and Right Ventricular Free Wall Longitudinal Strain, did not differ with age but was lower in males than in females. This is the first echocardiographic study to evaluate age- and sex-associated changes of cardiac morphometry and function in young and old NHP. The findings of this work will provide a reference to examine the effect of age and sex on cardiac diseases in NHP (Florio, 2024). Recent Previous work: A. We published that age is a crucial risk factor for cardiovascular (CV) and non-CV diseases. Standard Doppler echocardiography detects slow, normal, and accelerated heart ageing patterns. They predict CV and non-CV events, reflect biological age, and provide a new tool to calibrate prevention timing and intensity. (Ganau 2023) B. We published that ARA290 (cibinetide), an 11-aa non-hematopoietic peptide sequence within the cardioprotective domain of erythropoietin, mediates tissue protection by reducing inflammation and fibrosis. Administration of ARA290 reduces cell and tissue inflammation, mitigates structural and functional changes within the cardiovascular system leading to amelioration of frailty and preserved healthspan. (Winicki 2023) C. We published a paper examining the relationship between longitudinal changes in the ankle-brachialindex and muscle energy production in a community-dwelling population free of peripheral arterial disease. (Oberdier 2022). D. We published a paper examining the association between baseline carotid geometric phenotype andlongitudinal changes in arterial stiffness. (AlGhatrif 2023) II. Genetic and Environmental Underpinnings of Accelerated Cardiovascular Aging We published that aging is associated with a significant decline in aerobic capacity assessed by maximal exercise oxygen consumption (V̇o2max). The relative contributions of the specific V̇o2 components driving this decline, namely cardiac output (CO) and arteriovenous oxygen difference (A-V)O2, remain unclear. We examined this issue by analyzing data from 99 community-dwelling participants (baseline age: 21-96 yr old; average follow-up: 12.6 yr old) from the Baltimore Longitudinal Study of Aging, free of clinical cardiovascular disease. The age-associated decline in aerobic exercise performance over an average of 13 yr in community-dwelling healthy individuals is more closely associated with decreased peripheral oxygen utilization rather than decreased cardiac output. This association was more evident in older than younger individuals. These findings suggest that future studies with larger samples examine whether these associations vary across the age range and whether the decline in cardiac output plays a greater role earlier in life. In addition, studies focused on determinants of peripheral oxygen uptake by exercising muscle may guide the selection of preventive strategies designed to maintain physical fitness with advancing age. (AlGhatrif 2024)