Cellular Senescence, Vascular Disease, and Aging

Abstract

You must remember this, A kiss is just a kiss, A sigh is just a sigh, The fundamental things apply, As time goes by.-"As Time Goes By," by Herman Hupfeld, Casablanca (1942) 1 T he increasing prevalence of older-age people in our society represents the culmination of centuries of medical, scientific, and social endeavors. At least in Western society, now relatively freed from pestilence, abject poverty, gross malnutrition, and polluted water and food sources, an increasing proportion of the population can expect to make it to old age. However, although US age-adjusted death rates from cardiovascular disease, coronary heart disease, and stroke continue to fall, a disproportionate number of people who reach old age (Ϸ80% of people aged Ն80 years) suffer from these diseases. 1a In this 2-part review, we consider important pathobiological changes that occur with aging in the cardiovascular system, exploring promising areas of recent scientific progress and novel insights that may be translatable into targeted clinical strategies to help to alleviate the excess morbidity and mortality imposed by cardiovascular disease in the elderly. In this second installment, we focus specifically on vascular disease states of the elderly, including systolic hypertension, vascular calcification, and dementia, and we review relevant basic and clinical discoveries that further elucidate these conditions. Hardening of the Arteries: Calcification, Glycosylation, and the Vasculature in Old Age The Elderly Vascular PhenotypeAging is associated with various changes in the vascular system at differing structural and functional levels. At the macroscopic level, an increase in arterial lumen size and arterial wall thickening, mainly of the intima, are observed. 2 In addition, increased vascular calcification and a generalized stiffening of the arterial tree lead to increased arterial wave reflectance, increased systolic blood pressure, decreased diastolic blood pressure, and a widened pulse pressure.An interesting aspect of vascular biology in which significant inroads have been made is our understanding of pulse wave velocity, which is partly a consequence and partly a cause of the elderly vascular phenotype. In the healthy human arterial tree, the arterial pulse wave is reflected back toward the heart from branch points and other structures in the peripheral circulation, with the reflected wave arriving back at the aortic root during diastole. In older people, the stiffening of the vasculature results in higher forward and reflected pulse wave velocities, with the reflected wave arriving back at the aortic root in late systole, leading to an augmentation of the late systolic pressure (Figure 1). 3 This age-related shift of the reflected wave from diastole into late systole leads to an increased systolic workload for the heart, decreased coronary perfusion during diastole, and the transmission of higher pressures to end organs such as the brain and kidneys. 3 Therefore, stiffening of the vasculature is directly implicated in ventricula...

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…Typical age-associated aorta phenotypes are the vascular remodeling (VR) and the medial degeneration (MD) (see Fig. 3) [31][32][33][34][35][36][37][38][39][40]. Endothelial dysfunction, increased oxidative stress, inflammatory reaction, inflammatory cell infiltration in the aortic wall, apoptosis of VSMCs, degeneration of aortic media, and elastin fragmentation and degradation represent their microscopic alterations (see Fig.…”

“…Endothelial dysfunction, increased oxidative stress, inflammatory reaction, inflammatory cell infiltration in the aortic wall, apoptosis of VSMCs, degeneration of aortic media, and elastin fragmentation and degradation represent their microscopic alterations (see Fig. 3) [32][33][34][35][36][37][38]. These changes are responsible for the decline in aorta's elasticity [32][33][34][35][36][37][38].…”

“…3) [32][33][34][35][36][37][38]. These changes are responsible for the decline in aorta's elasticity [32][33][34][35][36][37][38]. As a result, the aorta dilates and mechanical expansion forces are transferred to ECM elements within the aortic wall, and in particular to collagen [32][33][34][35][36][37][38].…”

“…These changes are responsible for the decline in aorta's elasticity [32][33][34][35][36][37][38]. As a result, the aorta dilates and mechanical expansion forces are transferred to ECM elements within the aortic wall, and in particular to collagen [32][33][34][35][36][37][38]. In turn, this causes collagen remodeling within the tunica media, resulting in a stiffer and less compliant vessel.…”

Association of midlife obesity and cardiovascular risk with old age frailty: a 26-year follow-up of initially healthy men

“…3,5 In cross-sectional settings, or prospectively in later life, frailty has been associated with both clinical and subclinical cardiovascular disease (CVD). [11][12][13] Accelerated cardiovascular ageing 14 could be one explanation for the proposed relationship between frailty and CVD and also shared biological alterations, such as lowgrade inflammation, 15 may have a role. We have speculated earlier that development of frailty and weight loss therefore could also explain the 'obesity paradox' 16 -better prognosis among older people with overweight or obesity.…”