Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span

More VEGF, more life—and health span Advanced aging is celebrated but its ill effects, deterioration at the cell, tissue, and organ levels, are not. Grunewald et al . provide evidence for the vascular theory of aging, which reports that age-related decrease of vascular function is a driver of organi...

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Published in:Science (American Association for the Advancement of Science) 2021-07, Vol.373 (6554)
Main Authors: Grunewald, M., Kumar, S., Sharife, H., Volinsky, E., Gileles-Hillel, A., Licht, T., Permyakova, A., Hinden, L., Azar, S., Friedmann, Y., Kupetz, P., Tzuberi, R., Anisimov, A., Alitalo, K., Horwitz, M., Leebhoff, S., Khoma, O. Z., Hlushchuk, R., Djonov, V., Abramovitch, R., Tam, J., Keshet, E.
Format: Article
Language:English
Subjects:
Age
Aging
Alternative splicing
Angiogenesis
Biomedical materials
Blood vessels
Body composition
Bone loss
Bone tumors
Complications
Endothelial cells
Fatty liver
Growth factors
Health risks
Homeostasis
Hypoxia
Inflammation
Kyphosis
Life span
Metabolism
Microvasculature
Mitochondria
mRNA
Muscles
Organs
Osteoporosis
Oxygenation
Phenotypes
Rarefaction
Risk analysis
Risk factors
Sarcopenia
Senescence
Signal monitoring
Signal transduction
Signaling
Splicing
Tissues
Tumors
Upstream
Vascular diseases
Vascular endothelial growth factor
Vascular system
Viruses
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Summary:More VEGF, more life—and health span Advanced aging is celebrated but its ill effects, deterioration at the cell, tissue, and organ levels, are not. Grunewald et al . provide evidence for the vascular theory of aging, which reports that age-related decrease of vascular function is a driver of organismal aging at large (see the Perspective by Augustin and Kipnis). Vascular endothelial growth factor (VEGF) signaling insufficiency underlies this vascular insufficiency in aged mice. A modest compensatory increase in circulatory VEGF was sufficient to preserve a young-like vascular homeostasis, alleviate multiple adverse age-related processes, and ameliorate a host of age-associated pathologies in mice. —BAP Preventing age-associated deterioration of vascular function improves health span and life span in mice. INTRODUCTION All body cells rely on blood vessels (BVs) for the provision of oxygen and other blood-borne substances and, in certain settings, also for the provision of endothelial-derived paracrine factors. Like other organ systems, the vascular system undergoes aging, which leads to progressive functional deterioration. Given the centrality of BVs to organ homeostasis, it has been hypothesized that vascular aging is an upstream, founding factor in organismal aging, but experimental support for this proposition is limited. Vascular aging involves both large and small vessels, with the latter marked by capillary rarefaction, i.e., age-related failure to maintain adequate microvascular density (MVD). A key homeostatic mechanism preventing MVD reduction relies on the angiogenic activity of vascular endothelial growth factor (VEGF), which by virtue of its hypoxic inducibility, constantly acts to replenish lost vessels and match vascular supply to the tissue needs. The reason(s) that VEGF fails to do so during aging is unknown. RATIONALE Compromised vascular function is expected to perturb organ homeostasis in ways conducive for the development of age-related frailties and diseases. Accordingly, counteracting critical facets of vascular aging might be a useful approach for their alleviation. The presumption that insufficient vascular supply in aging is underlined by VEGF signaling insufficiency, primarily (but not exclusively) because of its indispensable role in preventing capillary loss, led us to investigate whether securing a young-like level of VEGF signaling might rectify capillary loss and its sequelae. On the premise that deteriorated vascular functi
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abc8479