Lack of evidence for GDF 11 as a rejuvenator of aged skeletal muscle satellite cells

Abstract

SummaryRecent high‐profile studies report GDF11 to be a key circulating ‘anti‐aging’ factor. However, a screen of extracellular proteins attempting to identify factors with ‘anti‐aging’ phenotypes in aged murine skeletal muscle satellite cells did not identify GDF11 activity. We have been unable to confirm the reported activity of GDF11, similar to other laboratories offering conflicting data and describe our attempts to do so in this short take.

Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease

“…Rather, GDF11 treatment dose-dependently increases ventricular myocyte hypertrophy in culture (Smith et al, 2015). Similarly, the beneficial influence of GDF11 on skeletal muscle regeneration following injury (Sinha et al, 2014) has been challenged (Egerman et al, 2015; Hinken et al, 2016). To establish relevance in humans and disentangle controversy, we measured GDF11 levels in a well-characterized patient population of older adults undergoing surgery for severe aortic stenosis.…”

“…The rejuvenative influence of GDF11 was called into question by Egerman et al, who showed that circulating GDF11 levels increase in rats and humans as a function of age and in fact, impede skeletal muscle regeneration (Egerman et al, 2015). Correspondingly, recent studies showed no effect of GDF11 on skeletal muscle satellite cell expansion in vitro (Hinken et al, 2016) and no cardiac improvements following daily delivery of recombinant GDF11 to 24-month old mice (Smith et al, 2015). The investigators who reported age-related decreases in GDF11 have also published corroborative results derived from antibody-based methods (Poggioli et al, 2016).…”

Rejuvenating Strategies for Stem Cell-Based Therapies in Aging

“…Interestingly, the effects in the brain are mediated by vascular remolding that promotes increased blood flow (Katsimpardi et al, 2014), yet the mechanism of action in other tissues is still unclear. The effects of GDF11 on skeletal muscle and its systemic changes with aging have recently been questioned (Egerman et al, 2015; Hinken et al, 2016; Poggioli et al, 2016; Schafer et al, 2016), calling for further studies to fully determine if this promising multi-target factor will be useful in therapies aimed at enhancing regenerative capacity.…”

Cellular and molecular mechanisms of sarcopenia: the S100B perspective

“…Mechanistically, myostatin was shown to increase ROS and TNF-α production in myoblasts, and the elevated TNF-α in turn stimulates myostatin expression with resultant proteasomal-mediated catabolism of intracellular proteins. 82 Instead, GDF11 is risk factor for age-related frailty and disease in humans. 78 In addition, cell senescence caused by telomere erosion; DNA damage; mitochondrial, proteostatic, and nutrient signalling dysfunction; and epigenetic factors is a central hallmark of aging: a combination of these conditions can induce senescence manifesting as the cell's inability to proliferate in response to appropriate stimuli owing to the hyperactivity of two main signalling pathways, p16 INK4a /Rb and p53/p21 CIP1 , which concur to repress cyclin-dependent kinase 4/6 (CDK4/6) activity ultimately leading to stem cell exhaustion 79 (Figure 3).…”