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Growth differentiation factor 11: A proangiogenic drug as a potential antiaging regulating molecule - 05/02/23

Doi : 10.1016/j.acvd.2022.09.006 
Luc Rochette a, , Geoffrey Dogon a, Eve Rigal a, Marianne Zeller a, Yves Cottin b, Catherine Vergely a
a Equipe d’Accueil (EA 7460): Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Faculté des Sciences de Santé, Université Bourgogne-Franche-Comté, 21000 Dijon, France 
b Service de Cardiologie, CHU de Dijon, 21000 Dijon, France 

Corresponding author at: Equipe d’Accueil (EA 7460): Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Faculté des Sciences de Santé, Université Bourgogne-Franche-Comté, 7, boulevard Jeanne d’Arc, 21000 Dijon, France.Equipe d’Accueil (EA 7460): Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Faculté des Sciences de Santé, Université Bourgogne-Franche-Comté7, boulevard Jeanne d’ArcDijon21000France

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Highlights

An organ such as the heart is characterized by limited regenerative capacity.
Organ rejuvenation can be mediated by blood-borne “proyouthful” factors.
GDF11, a member of the TGFβ cytokine superfamily, is a critical rejuvenation factor.
The neurovascular unit appears fundamental for brain metabolism.
The neurovascular unit is regulated by numerous endogenous modulators.
Restoring GDF11 blood levels may reverse physiological dysfunction in aged animals.

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Abstract

Organs and tissues are subjected to numerous alterations during aging, as a result of complex biochemical changes. Aging is certainly associated with the accumulation of “antiaging” and “proaging” factors in the systemic circulation. The effects of young blood on rejuvenation of regenerative capacity suggest the existence of multiple “proyouthful” factors, such as growth differentiation factor 11 (GDF11), in the young blood of animals. GDF11 is a member of the transforming growth factor beta (TGFβ) superfamily of cytokines, and appears to be a critical rejuvenation factor in aging organs. In the context of aging, GDF11 promotes vascular and neural plasticity of the central nervous system. Parabiosis, the surgical linking of circulations between old and young mice, was employed to identify GDF11 as an antihypertrophic factor that appears to rejuvenate the aging murine heart. Current theories suggest that GDF11 in young blood has beneficial effects on cognitive and cardiovascular functions and wound healing. The cellular mechanisms of GDF11 in cardiovascular, neurological, skin and skeletal muscle diseases are not clearly defined, but evidence indicates that it may function as a proneurogenic and proangiogenic drug. GDF11 binds and activates specific receptor complexes, which transmit signals by two procedures: the TGFβ-Smad pathway and the bone morphogenic protein (BMP)-Smad pathway. GDF11 is perhaps only the first in a series of circulating molecules that will be found to influence the aging of different tissues, and it may be a potential candidate for therapeutic intervention against angiogenesis-related disorders.

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Keywords : Regeneration, Angiogenesis, Rejuvenating factor, Aging, GDF11

Abbreviations : ALK, BMP, GDF, JAK, miRNA, MSC, MuSC, NLRP3, ROS, R-Smad, STAT-3, TGFβ, VSMC


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 Tweet: The effects of young blood on rejuvenation of regenerative capacity suggest the existence of multiple “proyouthful” factors, such as growth differentiation factor 11 (GDF11). GDF11 is a member of the transforming growth factor beta (TGFβ) superfamily of cytokines, it appears to be a pivotal rejuvenation factor in aging organs. Twitter address: @Eveu_08.


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Vol 116 - N° 1

P. 41-46 - janvier 2023 Regresar al número
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