image: Figure 4. The BM model secretes age-associated proteins. The BM model was statically cultured for five weeks. After two weeks, the BM cells were treated with either young or old human serum. On culture day 35, the BM cells were harvested, and the washed cell pellet analyzed using tandem LC-IMS-MS/MS proteomics. (A) Log2FC and −log2(p-value) of all significantly (p < 0.05) up (orange) or downregulated (turquoise) proteins in the BM with old serum compared to young serum. Proteins regulated in the same direction in at least 4 of 5 samples are depicted as well as either upregulated (red) or downregulated (blue). (B) Comparison of all regulated proteins to 2772 potentially secreted proteins according to the human protein atlas, creating an overlap of 233 proteins. (C) Go-Term analysis of down- (left) and up- (right) regulated overlapped proteins shown in (B). (D) Heatmap showing the log2FC of the overlapped 55 proteins in (E) depicting upregulated (red) and downregulated (blue) proteins with old serum. (E) Venn diagram showing the overlap of regulated proteins that belong to the human secretome (left) and secreted proteins that significantly change upon aging (right), resulting in 55 proteins shared between the two categories. (F) STRING protein network of the down- (left) and up- (right) regulated proteins from the 55 overlap proteins shown in (E). Expression by different BM cell types is highlighted with yellow circles (granulocytes), blue circles (progenitor cells) or violet circles (monocytes). Data were obtained from one experiment with 5 replicates.
Credit: Copyright: © 2025 Ritter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“[…] we were able to reproduce systemic rejuvenating effects of circulating blood factors on the human skin, which have been so far only demonstrated in rodent heterochronic parabiosis studies.”
BUFFALO, NY — August 1, 2025 — A new research paper featured on the cover of Volume 17, Issue 7 of Aging (Aging-US) was published on July 25, 2025, titled “Systemic factors in young human serum influence in vitro responses of human skin and bone marrow-derived blood cells in a microphysiological co-culture system.”
The study, led by first author Johanna Ritter and corresponding author Elke Grönniger from Beiersdorf AG, Research and Development Hamburg, shows that components in young human blood serum can help restore youthful properties to skin, but only when bone marrow cells are also present. This discovery highlights the role of bone marrow in supporting skin health and may allow for novel approaches aimed at slowing or reversing visible signs of aging.
The research explored how factors present in blood serum, already known to influence aging in animal studies, act on human cells. Using an advanced system that mimics human circulation, the researchers connected a 3D skin model with a 3D bone marrow model. They found that young human serum alone was not enough to rejuvenate skin. However, when bone marrow cells were present, these serum factors changed the activity of those cells, which then secreted proteins that rejuvenated skin tissue.
“Interestingly, we detected a significant increase in Ki67 positive cells in the dynamic skin model co-cultured with BM model and young serum compared to the model co-cultured with BM and old serum, indicating an improved regenerative capacity of the tissue.”
Detailed analysis indicated that young serum stimulated the bone marrow to produce a group of 55 proteins, with 7 of them demonstrating the ability to boost cell renewal, collagen production, and other features associated with youthful skin. These proteins included factors that improved energy production in cells and reduced signs of cellular aging. Without the interaction between skin and bone marrow cells, these rejuvenating effects did not occur.
This finding explains why earlier experiments in mice, where young and old animals shared a blood supply, showed rejuvenation across organs. It suggests that bone marrow-derived cells are critical messengers that transform signals from blood into effects on other tissues, including the skin.
While these results are preclinical and not from human trials, they offer a starting point for new strategies in regenerative medicine and skin care. By identifying specific proteins that may carry rejuvenating signals, the study points to a new way to address age-related changes. Researchers emphasize that further studies will be needed to confirm these effects in humans and to test how these proteins can be safely and effectively applied in future therapies.
Overall, this research is an important step in understanding how young blood serum factors influence human tissue and could guide the development of novel methods to maintain healthier skin as people age.
Read the full paper: DOI: https://doi.org/10.18632/aging.206288
Corresponding author: Elke Grönniger – elke.groenniger@beiersdorf.com
Keywords: aging, skin rejuvenation, microphysiological systems, systemic factors, bone marrow model, human serum
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Journal
Aging-US
Method of Research
News article
Subject of Research
Cells
Article Title
Systemic factors in young human serum influence in vitro responses of human skin and bone marrow-derived blood cells in a microphysiological co-culture system
Article Publication Date
25-Jul-2025
COI Statement
The authors declare no conflicts of interest related to this study.