GDF11 was identified in parabiosis studies as beneficially influencing stem cell and tissue function. Levels of GDF11 decline with age. There was some debate over whether or not the early research was correct, but GDF11 is presently in clinical development as a basis for regenerative therapies for the old. Researchers here outline a role of GDF11 in the regeneration and tissue maintenance of skin, focusing on its anti-inflammatory role. The chronic inflammation of aging is present in all tissues, skin included, and is detrimental to health and tissue function. Anti-inflammatory effects are likely important in the observed benefits from upregulation of GDF11 in old animals.
GDF11 regulates essential cell differentiation and proliferation responses and is expressed in numerous tissues, including the skin, heart, skeletal muscle, and developing nervous system. Its expression is at the highest level in young adult organs and seems to decline during aging. Some studies have shown that GDF11 can reverse age-related dysfunction in muscle, nervous and cardiovascular systems. Although serum GDF11 levels were found to be decreased in old mice, supplementation with GDF11 "rejuvenated" them, thereby suggesting that GDF11 is a key player in mammalian life span. It has also been suggested that GDF11 is involved in the age-related global physiological decline in function, and that restoring circulating blood levels of GDF11 could reverse some of the cellular and physiological dysfunctions observed in aged mice.
Tumor necrosis factor-α (TNF-α) plays a key role in inflammatory diseases, including skin inflammation, while GDF11 inhibits inflammatory reactions. GDF11 treatment antagonizes TNF-α-induced inflammation in macrophages, and the administration of GDF11 appears to attenuate skin inflammation. Studies show that TNF-α-induced activation of the nuclear factor kappa B (NF-κB) signaling pathway, which is known to participate in various inflammatory conditions, is limited by GDF11 treatment.
Heat shock proteins (HSPs) are molecular chaperones essential for the maintenance of cellular functions, but they can be released extracellularly upon cellular injury or necrosis. GDF11 induces protective effects in various tissues through the suppression of oxidative stress and the expression of HSPs. As the key member of the TGF-β superfamily, GDF11 represents a promising therapeutic agent for the treatment of a number of inflammatory skin diseases, including psoriasis.