The Pressure of Aging

Abstract

Significant hemodynamic changes ensue with aging, leading to an ever-growing epidemic of hypertension. Alterations in central arterial properties play a major role in these hemodynamic changes. These alterations are characterized by an initial decline in aortic distensibility and a rise of diastolic blood pressure, followed by a sharp increase in pulse wave velocity (PWV), and a rise in pulse pressure (PP) beyond the sixth decade. However, the trajectories of PWV and PP diverge with advancing age, more profoundly in men than women, likely reflecting the more pronounced aortic dilatation in men. There is an increased prevalence of salt-sensitive hypertension with advancing age, that is, in part, mediated by marinobufagenin, an endogenous sodium pump ligand, which is also linked to central arterial stiffness. Within the arterial wall, biomechanical and humoral changes are accompanied by significant biomolecular alterations producing a proinflammatory state, in which activation of angiotensin II signaling plays a pivotal role. This proinflammatory state is in origin a reparatory response to a damaged arterial wall under a pulsatile injury. However the same reparatory process results in fibrosis, which in turn worsens arterial stiffness and produce more pulsatile hemodynamics; this relationship between the pulsatile damage and proinflammatory state is best described as a feed-forward loop. Effective efforts to counter the surging epidemic of hypertension with the aging of our population should be aimed at revealing early, pre-clinical hemodynamic and arterial wall alterations, and develop interventions that halt these processes before they reach the stage the medical community defined as “disease”.

Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks

“…The statistical analysis was designed to account for these potential biases, as far as the data allowed. Inclusion of participants of different age groups further augments variability in terms of resting metabolic rate (Peng et al, 2014), resting cerebral blood flow (Lu et al, 2011), vascular CO 2 reactivity (Lu et al, 2011; Murphy et al, 2013); blood pressure (AlGhatrif et al, 2017); and hemoglobin concentration (Patel, 2008) all known to affect BOLD fMRI signal and/or the coupling of neural activity to the BOLD signal (D’Esposito et al, 1999; Levin et al, 2001; Patel et al, 2012; Murphy et al, 2013; Mark et al, 2015). Nevertheless, the uneven effect of aging on large-scale brain networks (e.g., DMN vs. MN), emphasized here and elsewhere (Song et al, 2014; Marstaller et al, 2015), probably indicates that age-related FC alterations cannot be merely attributed to changes in neurovascular coupling.…”

The tripartite interaction of phosphate, autophagy, and αKlotho in health maintenance

“…Each treatment has 5 mice. D, Co-immunoprecipitation of beclin 1 and BCL2 in total kidney lysates from 5 mice presented in Figure 6B (1) Because no αKlotho knockout line was used in this study, we are not able to investigate whether beclin 1 prolongs mouse life span completely independently of αKlotho. Based on the time course of plasma Pi and αKlotho during BK/BK;kl/kl mice development, and the rapamycin effect on kl/kl mice, we proposed that beclin 1-induced phosphaturia decreases plasma Pi, consequently restoring αKlotho and rescuing prematuring age phenotypes.…”

“…Aging is an inevitable multi-organ deterioration initiated and accelerated by genetic, epigenetic, and environmental factors; among which is the lesser known factor of inorganic phosphate (Pi) intake in excess of the need of the organism. [1][2][3] Excessive Pi intake is highly prevalent in the developed world. 4 The ill effects of excess Pi at the cellular, organ, and whole organism levels are collectively termed "phosphotoxicity".…”

Analysis on the Status Quo and Influencing Factors of the “Five Conceptions and Six Features” Community Courtyard Pension Model in Nanchang

“…With economic and social development, human life expectancy has been extended by 10 -20 years in recent decades [13] [14]. The accumulation of the elderly population has brought great challenges to individuals, families and society [15]. The rate of the only child in the survey was 50.68%.…”