Targeting the redox system for cardiovascular regeneration in aging

Abstract

Cardiovascular aging presents a formidable challenge, as the aging process can lead to reduced cardiac function and heightened susceptibility to cardiovascular diseases. Consequently, there is an escalating, unmet medical need for innovative and effective cardiovascular regeneration strategies aimed at restoring and rejuvenating aging cardiovascular tissues. Altered redox homeostasis and the accumulation of oxidative damage play a pivotal role in detrimental changes to stem cell function and cellular senescence, hampering regenerative capacity in aged cardiovascular system. A mounting body of evidence underscores the significance of targeting redox machinery to restore stem cell self‐renewal and enhance their differentiation potential into youthful cardiovascular lineages. Hence, the redox machinery holds promise as a target for optimizing cardiovascular regenerative therapies. In this context, we delve into the current understanding of redox homeostasis in regulating stem cell function and reprogramming processes that impact the regenerative potential of the cardiovascular system. Furthermore, we offer insights into the recent translational and clinical implications of redox‐targeting compounds aimed at enhancing current regenerative therapies for aging cardiovascular tissues.

Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging

“…Our findings also confirmed that PAA induces morphological and metabolic changes in aortic ECs that lead to cellular senescence and consequently impairment of angiogenesis. Corroborating these results, our and others’ previous studies demonstrated that accumulation of senescent ECs plays a causative role in pathogenesis of vascular diseases such as atherosclerosis 1,33 . Therefore, the gut-derived PAA can be potentially suggested as a key determinant in the induction of endothelial senescence and the development of atherosclerosis upon aging.…”

AQP1 Differentially Orchestrates Endothelial Cell Senescence

“…Our findings showed that AQP1 is essential for HDAC4 phosphorylation at Serine site 632, which subsequently controls its nuclear export, in proliferating ECs. It returns to the fact that redox/metabolic status in ECs orchestrates permanent changes in their epigenetic programming [2]. The CaMKII-mediated hierarchical phosphorylation of HDAC4 S632 facilitates its subcellular localization [22].…”

“…It has been postulated that endothelial cells undergo permanent alterations in their metabolic and redox states during aging [2,6]. The stable ROS, H 2 O 2 , at higher concentrations, alters mitochondrial dynamics, impairs respiratory chain activity, and disrupts redox homeostasis [2].…”

“…It has been postulated that endothelial cells undergo permanent alterations in their metabolic and redox states during aging [2,6]. The stable ROS, H 2 O 2 , at higher concentrations, alters mitochondrial dynamics, impairs respiratory chain activity, and disrupts redox homeostasis [2]. It has become clear that disrupted mitochondrial respiration and energy metabolism may drive cellular senescence and dysfunction in these cells [25].…”

“…Aging, a significant risk factor for cardiovascular diseases, is characterized by cellular senescence [1,2]. This phenomenon is a permanent cell cycle arrest linked to accumulated stochastic cellular damage [3,4].…”