“Heterochronic parabiosis studies illuminated the potential for rejuvenation through blood-borne factors, yet the specific drivers including underlying mechanisms remain largely unknown and until today insights have not been successfully translated to humans.”
A new study published as the cover of Aging (Aging-US) Volume 17, Issue 7, explores how factors in young human blood may affect the biological age of human skin. Researchers from Beiersdorf AG, Research and Development Hamburg in Germany, used a microphysiological co-culture system—a lab-based model simulating human circulation—to test the effects of young versus old blood serum on skin cells. The findings suggest that bone marrow-derived cells play a key role in converting blood-borne signals into effects that support skin rejuvenation.
Understanding Skin Aging and Systemic Influence
As we age, the skin’s ability to regenerate declines, while its biological age increases. This contributes to visible signs of aging and a weakened barrier function. While cosmetic treatments can improve appearance, they rarely target the cellular processes underlying skin aging.
Animal studies have shown that exposure to young blood can promote tissue repair and rejuvenation, likely due to molecules circulating in the bloodstream. However, reproducing these effects in human skin has proven difficult. Applying young serum directly to skin tissue has not produced significant results, indicating that additional cellular interactions may be required.
The Study: A Two-Step Regenerative Protocol
The research team, led by first author Johanna Ritter and corresponding author Elke Grönniger from Beiersdorf AG, developed an innovative in vitro system combining two engineered human tissue models: full-thickness skin and bone marrow. Using the HUMIMIC Chip3plus platform, they created a miniature circulatory system where these tissues could interact through shared culture media.
The study, 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,” investigated how human serum from young (<30 years) and older (>60 years) donors influenced markers of skin aging over a 21-day period.
Results: Rejuvenation Dependent on Bone Marrow Interaction
The researchers observed that young serum alone had no effect on skin aging markers in either static or dynamic skin-only cultures. However, when skin tissue was co-cultured with bone marrow-derived cells, significant changes occurred.
Skin in the combined system treated with young serum showed increased cell proliferation, indicating improved regenerative potential, and a reduction in biological age as measured by DNA methylation clocks. Bone marrow cells also exhibited improved mitochondrial function and changes in cell composition, particularly an increase in early progenitor cells.
These findings suggest that bone marrow-derived cells respond to young serum by producing signaling proteins that influence skin behavior. Without these intermediary cells, the rejuvenating effects were not observed.
Further proteomic analysis identified 55 proteins that were differentially expressed in bone marrow cells exposed to young versus old serum. Of these, seven proteins were tested individually on aged skin cells. Several—including CHI3L1, CD55, and MMP-9—improved markers related to skin aging, such as collagen production, mitochondrial activity, and cellular plasticity.
The Impact: Identification of Key Rejuvenating Proteins
This discovery highlights specific proteins that may serve as future targets in skin regeneration research. While the results are promising, they were obtained in controlled lab conditions. These findings are not yet applicable to clinical treatments but offer a potential foundation for developing non-invasive skin therapies that mimic the effects of youthful blood composition.
Future Perspectives and Conclusion
The study underscores the importance of systemic and inter-organ communication in skin aging. By incorporating bone marrow-derived cells into the experimental model, the researchers created a more physiologically accurate system to study how circulating factors influence tissue aging.
Although the evidence supports the idea that bone marrow cells mediate the effects of young serum on skin, additional research is needed. Future studies using aged skin models, extended time frames, and clinical validation will be essential to explore therapeutic possibilities.
As an experimental approach, this research adds valuable knowledge to the biological mechanisms of skin aging and could inform future strategies in regenerative medicine and dermatology.
Click here to read the full research paper published in Aging (Aging-US).
___
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
Click here to subscribe to Aging publication updates.
For media inquiries, please contact [email protected].