The influence of GDF11 on brain fate and function

Abstract

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.

Decreased Plasma Levels of Growth Differentiation Factor 11 in Patients With Schizophrenia: Correlation With Psychopathology and Cognition

“…Our present findings show a significant decrease in plasma GDF-11 levels in schizophrenia patients, and GDF-11 level was related to the psychopathological symptoms and cognitive impairments. In combination with the roles of GDF-11 in neurogenesis and brain function (15,29,31) and the effects of GDF-11 on nerve development and cell regulations (32)(33)(34), it is indicated that GDF-11 may be related to the pathophysiology of schizophrenia. However, it should be noted that the difference in plasma GDF-11 levels between the patient and control groups could result from schizophrenia itself or other potential influence factors, such as the effect of antipsychotics.…”

Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction‐like phenotype in aged mice

“…Subsequently, other reports argued that GDF11 was positively associated with aging, cachexia, and inhibition of muscle regeneration in aged mice (Egerman et al, ; Harper et al, ; Jones et al, ), while different studies showed a beneficial role for GDF11 in the periphery (Poggioli et al, ; Su et al, ; Walker et al, ). In the central nervous system, GDF11 was also shown to be neuroprotective for neurovascular recovery and neurogenesis (Anqi, Ruiqi, Yanming, & Chao, ; Ma et al, ; Ozek, Krolewski, Buchanan, & Rubin, ; Schafer & LeBrasseur, ; Zhang et al, ).…”

Detection of the myostatin‐neutralizing antibody Domagrozumab in serum by means of Western blotting and LC‐HRMS

“…As shown in Supporting Information Figure S1, the anti‐myostatin antibody was found to bind both myostatin and GDF‐11 with similar affinity. Analogous to myostatin, GDF‐11 functions as a negative regulator of neurogenesis in the developing central nervous system (CNS) . Both proteins share 90% sequence homology, which explains why Domagrozumab can bind to both growth factors.…”

“…Analogous to myostatin, GDF-11 functions as a negative regulator of neurogenesis in the developing central nervous system (CNS). 32 Both proteins share 90% sequence homology, which explains why Domagrozumab can bind to both growth factors. As GDF-11 is significantly cheaper than myostatin, this cytokine was chosen for immunoaffinity purification and different amounts were coupled to NHS magnetic sepharose (see 2.3.2).…”