Impact of Geroscience on Therapeutic Strategies for Older Adults With Cardiovascular Disease: JACC Scientific Statement

Abstract

Geroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan. Here, we describe the main resilience mechanisms of mammalian aging, with a focus on how they can affect CVD pathophysiology. We next present novel gerotherapeutic approaches, some of which are already used in management of CVD, and explore their potential to transform care and management of CVD. The geroscience paradigm is gaining traction broadly in medical specialties, with potential to mitigate premature aging, reduce health care disparities, and improve population healthspan.

Keywords: frailty; geroscience; hallmarks; inflammation; multimorbidity.

CENTRAL ILLUSTRATION

The Geroscience Hypothesis in the Context of Cardiovascular Disease Genetic predisposition and unhealthy behaviors (blue arrows) contribute to major CVD risk factors and CVD in older persons. Aging itself is associated with stochastic damage to molecules and organelles (pink arrows) and accelerates risks of CVD, as well as multimorbidity, frailty, disability, and premature death. Whereas resilience signifies capacity to repair or replace such damaged components, resilience often diminishes over time, especially amid behavioral risk factors (eg, unhealthy diet) and chronic diseases (green arrows). The geroscience hypothesis poses that enhancing resilience reduces the burden of CVD and other chronic diseases and related susceptibility to frailty and disability. AD/ADRD = Alzheimer disease and Alzheimer disease-related dementias; CAD = coronary heart disease; COPD = chronic obstructive pulmonary disease; CVD = cardiovascular disease; ECM = extracellular matrix; HF = heart failure; LDL = low-density lipoprotein; OA = osteoarthritis; PAD = peripheral arterial disease; QC = quality control.

FIGURE 1

The Hallmarks of Aging Biological processes that become impaired with aging can be potentially targeted by gerotherapeutics. The intersecting lines depict how targeting each pillar can affect the others. QC = quality control.

FIGURE 2

Aging Hallmarks and Cardiovascular Disease Heat map providing a visual representation of the strength of evidence in the literature implicating hallmarks of aging in cardiovascular disease (CVD). See Supplemental Figure 1 for added detail regarding the associated references. A, Genomic stability and systolic hypertension. B, Genomic stability and heart failure with preserved ejection fraction (HFpEF). C, Genomic instability and atrial fibrillation. D, Epigenetics and amyloid. E, Epigenetics and systolic hypertension. F, Telomere modification and atrial fibrillation. G, Loss of proteostasis, mitochondrial dysfunction, and amyloid. H, Deregulated nutrient sensing and atrial fibrillation.

FIGURE 3

Pleotropic Effects of Gerotherapeutics Aging mechanisms are interconnected such that an intervention targeting a single hallmark of aging or multiple hallmarks of aging also exerts downstream effects on varied other hallmarks of aging. As a result of such interactions among varied biological hallmarks of aging, an intervention targeting a single hallmark can exert variable effects on multiple chronic diseases and geriatric syndromes. An ideal gerotherapeutic intervention moderates multiple hallmarks to prevent disease and geriatric conditions. QC = quality control.