Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Department of Physical Medicine and Rehabilitation, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Geroscience. 2019 Feb;41(1):1-11. doi: 10.1007/s11357-019-00054-6. Epub 2019 Feb 7.
Growth differentiation factor 11 (GDF11) is a transforming growth factor β (TGFβ) protein that regulates aspects of central nervous system (CNS) formation and health throughout the lifespan. During development, GDF11 influences CNS patterning and the genesis, differentiation, maturation, and activity of new cells, which may be primarily dependent on local production and action. In the aged brain, exogenous, peripherally delivered GDF11 may enhance neurogenesis and angiogenesis, as well as improve neuropathological outcomes. This is in contrast to a predominantly negative influence on neurogenesis in the developing CNS. Seemingly antithetical effects may correspond to the cell types and mechanisms activated by local versus circulating concentrations of GDF11. Yet undefined, distinct mechanisms of action in young and aged brains may also play a role, which could include differential receptor and binding partner interactions. Exogenously increasing circulating GDF11 concentrations may be a viable approach for improving deleterious aspects of brain aging and neuropathology. Caution is warranted, however, since GDF11 appears to negatively influence muscle health and body composition. Nevertheless, an expanding understanding of GDF11 biology suggests that it is an important regulator of CNS formation and fate, and its manipulation may improve aspects of brain health in older organisms.
生长分化因子 11（GDF11）是一种转化生长因子β（TGFβ）蛋白，可调节整个生命周期中枢神经系统（CNS）形成和健康的各个方面。在发育过程中，GDF11 影响 CNS 模式形成以及新细胞的发生、分化、成熟和活性，这可能主要依赖于局部产生和作用。在衰老的大脑中，外源性、外周递送至的 GDF11 可能增强神经发生和血管生成，并改善神经病理学结果。这与 GDF11 在发育中的 CNS 中对神经发生的主要负面影响形成对比。看似矛盾的作用可能与局部和循环 GDF11 浓度激活的细胞类型和机制相对应。然而，年轻和衰老大脑中未定义的、不同的作用机制也可能起作用，其中包括差异受体和结合伴侣相互作用。外源性增加循环 GDF11 浓度可能是改善大脑衰老和神经病理学有害方面的可行方法。然而，需要谨慎，因为 GDF11 似乎会对肌肉健康和身体组成产生负面影响。尽管如此，对 GDF11 生物学的不断深入理解表明，它是 CNS 形成和命运的重要调节剂，其操纵可能会改善老年生物的大脑健康状况。
