Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction-like phenotype in aged mice.,Aging Cell

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Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction-like phenotype in aged mice.
Aging Cell ( IF 8.0 ) Pub Date : 2019-10-22 , DOI: 10.1111/acel.13038
Lida Katsimpardi _{1,

2} , Nicolas Kuperwasser ₃ , Claire Camus _{1,

2} , Carine Moigneu _{1,

2} , Aurélie Chiche ₄ , Virginie Tolle ₅ , Han Li ₄ , Erzsebet Kokovay ₆ , Pierre-Marie Lledo _{1,

2}

Affiliation

Aging is a negative regulator of general homeostasis, tissue function, and regeneration. Changes in organismal energy levels and physiology, through systemic manipulations such as calorie restriction and young blood infusion, can regenerate tissue activity and increase lifespan in aged mice. However, whether these two systemic manipulations could be linked has never been investigated. Here, we report that systemic GDF11 triggers a calorie restriction‐like phenotype without affecting appetite or GDF15 levels in the blood, restores the insulin/IGF‐1 signaling pathway, and stimulates adiponectin secretion from white adipose tissue by direct action on adipocytes, while repairing neurogenesis in the aged brain. These findings suggest that GDF11 has a pleiotropic effect on an organismal level and that it could be a linking mechanism of rejuvenation between heterochronic parabiosis and calorie restriction. As such, GDF11 could be considered as an important therapeutic candidate for age‐related neurodegenerative and metabolic disorders.

中文翻译：

全身性GDF11刺激衰老小鼠的脂联素分泌并诱导出类似卡路里限制的表型。

衰老是总体稳态，组织功能和再生的负面调节器。通过系统的操作（例如限制热量和输注年轻血液）来改变机体能量水平和生理机能，可以再生组织活性并延长衰老小鼠的寿命。但是，这两个系统操作是否可以链接起来从未被研究过。在这里，我们报道全身性GDF11触发了类似卡路里限制的表型，而不影响血液中的食欲或GDF15水平，恢复了胰岛素/ IGF-1信号通路，并通过对脂肪细胞的直接作用而刺激了白色脂肪组织中脂联素的分泌，同时进行了修复。老年大脑中的神经发生。这些发现表明，GDF11在机体水平上具有多效作用，并且它可能是异时共生和卡路里限制之间的复兴的联系机制。因此，GDF11可以被认为是与年龄有关的神经退行性和代谢性疾病的重要治疗候选药物。

更新日期：2019-10-22

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