Turning Back the Aging Clock: New Insights into Epigenetic Modulation in Skin Cells

By Fred Zülli, Mibelle Biochemistry

Understanding Aging: The Science Behind Biological and Epigenetic Age

When we talk about aging, most people think of chronological age - the number of years we have lived. However, our biological age offers a far more accurate reflection of our body’s health and vitality. One of the most promising indicators of biological age is epigenetic age, which is determined by DNA methylation patterns. Tools like the Horvath clock have revolutionized our ability to measure these changes, providing detailed information on how our cells age at the molecular level.

The Horvath Clock is a pioneering DNA methylation-based aging clock developed by Dr. Steve Horvath which has been validated in numerous studies and is widely used in aging research, forensic science, and clinical trials.

At Mibelle Biochemistry, we set out to explore the epigenetic aging process in skin cells, focusing on fibroblasts and dermal stem cells. Our goal? To uncover how these cells age and identify potential pathways for intervention.

Why Epigenetic Age Matters for Skin Health

Skin is not only our largest organ but also one of the most visible indicators of aging. Unlike chronological age, epigenetic age is positively and negatively influenced by both intrinsic factors (genetics, metabolism) and extrinsic influences (UV exposure, pollution). By measuring the epigenetic age of the skin, one can now better understand the current status of the skin and follow the efficacy of interventions over time. Understanding this process is key to developing innovative cosmetic solutions that target aging at its root.

Our Research Approach

To study epigenetic aging, we used two complementary models:

• Fibroblast cultures (Hayflick Model): This classic model allowed us to observe aging in vitro. Cells are grown in cell culture for weeks for several cell passages which mimics the aging process as primary cells only have a finite number of cell divisions they can undergo before becoming senescent. Samples can be taken at different time points to follow aging-related changes.
• Dermal stem cells from young (<30 years) and old (>70 years) donors: These cells were analyzed for age-related changes in DNA methylation and gene expression. Here, the aging process has happened in the individuals and differences between old and young donors can be investigated. 

We applied cutting-edge techniques, including:

• Horvath skin & blood clock for epigenetic age measurement.
• Genome-wide DNA methylation analysis (Infinium EPIC v2.0, Illumina).
• Transcriptomic profiling using Bulk RNA Barcode Sequencing (BRBseq).

Key Findings

• Fibroblast Aging: Epigenetic age increased with passage number, correlating strongly with age-related DNA methylation changes. This was validated by higher SA-beta-galactosidase activity, a classic senescence marker. This means that the Horvarth clock can be used to track the aging of skin cell in vitro. 
• Dermal Stem Cells: Cells from older donors showed clear epigenetic aging compared to younger ones. Surprisingly, transcriptomic analysis revealed only a small number of significantly altered genes - primarily linked to alternative splicing pathways.

These insights suggest that while epigenetic changes are profound, gene expression shifts are more subtle, pointing to specific molecular targets for intervention.

What This Means for Skin Care

Our findings confirm that skin cells undergo intrinsic aging processes that can be tracked using advanced molecular tools. This opens exciting possibilities for cosmetic formulations designed to modulate epigenetic aging, potentially restoring youthful functionality to skin cells.
Future research will focus on whether active ingredients can slow or reverse these epigenetic changes - paving the way for next-generation anti-aging solutions.

Reference

(1) Julia Baumann, Valentine Vocat, Kathrin Novak, Fred Zuelli, Chennakesava Cuddapha and Franziska Wandrey: Bulk RNA Barcode Sequencing Reveals Role of RNA Splicing in Aging Dermal Stem Cell Modulation by a Botanical Extract. Cosmetics 2024, 11(5), 167. 

Want to learn more about our research and innovative ingredients?

👉 Please also note Fred Zülli's lecture on this topic at the SSC79, Session J: Skin Wellness,  December 17, 2025 from 2:45 pm - 4:45 pm
👉 Visit Mibelle Biochemistry’s webpage for detailed insights and product solutions. Cosmetic ingredient supplier | Mibelle Biochemistry
👉Contact Mibelle Biochemistry USA for more information: info@mibellegroupusa.com

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