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

M. Grunewald, S. Kumar, H. Sharife, E. Volinsky, A. Gileles-Hillel, T. Licht, A. Permyakova, L. Hinden, S. Azar, Y. Friedmann, P. Kupetz, R. Tzuberi, A. Anisimov, K. Alitalo, M. Horwitz, S. Leebhoff, O. Z. Khoma, R. Hlushchuk, V. Djonov, R. AbramovitchJ. Tam, E. Keshet

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, "inflammaging" (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.

Original languageAmerican English
Issue number6554
StatePublished - 30 Jul 2021

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Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.


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