The rejuvenating effects of systemic factors from young human serum on human skin : Insights from bone marrow-derived proteins

Systemic factors circulating through the bloodstream affecting multiple organs at the same time, hold great potential to be central regulators during the aging process of human tissues. As life expectancy continues to increase, there is a corresponding rise in the prevalence of age-associated diseases, including cancer and various dermatological disorders. The skin, as the largest organ of the human body and the primary barrier protecting internal organs, serves as an ideal model system to investigate rejuvenation processes in general, but is also of relevance for cosmetic science. Rejuvenation through systemic factors was first proven by heterochronic parabiosis experiments, where the blood circulation of two animals of different ages were joined resulting in improved characteristics of the aged individual, including a rejuvenated skin. While these experiments provided valuable insights into rejuvenation mechanisms, they could not be fully translated to human systems yet.
In this study, a human skin and bone marrow model, cultured in a microphysiological system enabled to emulate heterochronic parabiosis in vitro through the addition of either young or old human serum. Thereby, for the first time, rejuvenation of human skin tissue through increased regeneration capacity and reduced biological age in the presence of BM-derived cells comparing young human serum treatment to old human serum treatment, was achieved. Subsequent proteomics analysis of the bone marrow model revealed age-related proteins in response to old versus young human serum, being secreted to the blood circulation, thereby potentially affecting other tissues, such as the skin. Their rejuvenation potential was validated holistically on old skin cells, by measuring the epigenetic age and seven hallmarks of skin aging. Promising central systemic factors were identified, holding the potential to reverse skin aging.

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