Reviewing the Role of GDF11 in Aging

In heterochronic parabiosis, the circulatory systems of an old and young animal are connected. The young animal exhibits some aspects of accelerated aging, while the old animal exhibits some degree of rejuvenation. Early investigations focused on the supply of factors in young blood to the old animal as the causative mechanism, and GDF11 was one of the first such factors identified for further research and development. There has been some controversy over the published works on this topic, however, stemming initially from technical issues involved in working with GDF11, then later from investigations that point to dilution of harmful factors in old blood being the dominant mechanism in heterochronic parabiosis. The company Elevian claims to have resolved these issues, and is advancing therapies based on delivering GDF11, but it will probably be at least a few more years before there is a clear view into the details of their work.

Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily, has recently received attention because of its numerous functions in modulating the development and differentiation of various tissues and organs. Studies regarding the role of GDF11 in the development of various diseases have been conducted in recent decades. GDF11 is reportedly beneficial with respect to controlling age-related cardiac hypertrophy, improving muscle tone, preventing degeneration in the central nervous system, enhancing cognitive function, and promoting tissue regeneration.

Important parabiosis experiments involving two animals of different ages, performed in 2013 and 2014, revealed that GDF11 levels were disrupted in an age-related manner in vascular, neurogenic, and skeletal muscle tissues. Those findings suggested that GDF11 may be regarded as an honorable "rejuvenation" factor that could restore regenerative function, thus resisting aging and extending longevity. A study in fish revealed that GDF11 has rejuvenation capacity to extend the lifespan. In 2020, a plasma proteomic dataset demonstrated that the GDF11 protein can significantly extend the lifespan.

These studies demonstrated critical roles for GDF11 in the inhibition of aging. However, recent studies have yielded conflicting data regarding the ability of GDF11 to alleviate dysfunction in age-related diseases. Thus, the regeneration ability of GDF11 with respect to age-related dysfunction requires further investigation. This review provides an overview of GDF11 and its functions in age-related diseases. It also discusses potential underlying mechanisms for the effects of GDF11 in age-related diseases.

Link: https://doi.org/10.18632/aging.202881

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