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

被引：239

作者：

Grunewald, M. ^{[1
]}

Kumar, S. ^{[1
]}

Sharife, H. ^{[1
]}

Volinsky, E. ^{[1
]}

Gileles-Hillel, A. ^{[1
,2
,3
,4
]}

Licht, T. ^{[1
]}

Permyakova, A. ^{[5
]}

Hinden, L. ^{[5
]}

Azar, S. ^{[5
]}

Friedmann, Y. ^{[6
]}

Kupetz, P. ^{[1
]}

Tzuberi, R. ^{[1
]}

Anisimov, A. ^{[7
]}

Alitalo, K. ^{[7
]}

Horwitz, M. ^{[1
]}

Leebhoff, S. ^{[1
]}

Khoma, O. Z. ^{[8
]}

Hlushchuk, R. ^{[8
]}

Djonov, V ^{[8
]}

Abramovitch, R. ^{[2
,3
]}

Tam, J. ^{[5
]}

Keshet, E. ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Fac Med, Jerusalem, Israel

[2] Hadassah Hebrew Univ Hosp, Wohl Inst Translat Med, Jerusalem, Israel

[3] Hadassah Hebrew Univ Hosp, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel

[4] Hadassah Med Ctr, Dept Pediat, Pediat Pulmonol & Sleep Unit, Jerusalem, Israel

[5] Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Obes & Metab Lab,Inst Drug Res, Jerusalem, Israel

[6] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Bio Imaging Unit, Jerusalem, Israel

[7] Univ Helsinki, Res Programs Unit, Translat Canc Biol Program, Fac Med, Helsinki, Finland

[8] Univ Bern, Inst Anat, Topog & Clin Anat, Bern, Switzerland

来源：

SCIENCE | 2021年 / 373卷 / 6554期

基金：

以色列科学基金会;

关键词：

ENDOTHELIAL GROWTH-FACTOR; LONGEVITY; NEOVASCULARIZATION; MECHANISMS; INSIGHTS; PROVIDES; SYSTEM; MUSCLE; LIVER;

D O I：

10.1126/science.abc8479

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：533 / +

页数：57

共 43 条

[1] Activated Forms of VEGF-C and VEGF-D Provide Improved Vascular Function in Skeletal Muscle [J].