Ageing is a natural process that manifests visibly on our skin through wrinkles, fine lines, and pigmentation. As science delves deeper into understanding ageing, one of the notable discoveries has been retinoic acids, particularly tretinoin, in anti-ageing skincare. This blog explores the benefits and limitations of tretinoin and how epigenetics can be utilized to track the molecular benefits of such products on the skin.
Tretinoin, a derivative of vitamin A, is widely regarded as the gold standard in anti-ageing treatments. Its effectiveness lies in its ability to accelerate cell turnover, promote collagen production, and improve skin texture and tone. Clinical studies have shown that tretinoin can reduce the appearance of fine lines, wrinkles, and pigmentation, making it a staple in dermatological treatments.
Unlike over-the-counter retinoids such as retinol, tretinoin is a prescription-based medication. This means it is stronger and requires supervision from a healthcare provider due to its potent effects and potential side effects. Tretinoin works more quickly than retinol as it does not need to be converted by the skin’s enzymes, making it a powerful agent against both acne and signs of ageing.
Limitations of Tretinoin
Despite the benefits, tretinoin is not without limitations. The most common side effects include redness, irritation, dryness, and peeling, particularly during the initial phase of use. These side effects can deter some users from continuing treatment. Additionally, tretinoin makes the skin more sensitive to sunlight, necessitating rigorous use of sunscreen to prevent further damage.
Epigenetics: A New Frontier in Skincare Research
Understanding Epigenetics
Epigenetics involves the study of changes in gene expression via chemical changes like DNA methylation on the surface of the DNA that do not change the DNA sequence. These changes can be influenced by various factors, including environmental and lifestyle choices. In the context of skincare, epigenetic research can provide insights into how treatments like tretinoin influence skin at a molecular level.
Tracking Molecular Benefits Through Epigenetics
In search of answers on how tretinoin might influence the epigenetic landscape of the skin, Mitra Bio organized a pilot study involving 6 participants to explore the impact and change of biological ageing with topical tretinoin over 2 months. The pilot study involved non-invasive sampling to collect skin cells for sequencing and analysis of DNA methylation profiles of participants undergoing a 56-day tretinoin regimen (1).
Epigenetic Changes: The study found an increase in DNA methylation after 56 days of tretinoin use. These changes were associated with key pathways related to skin longevity, including immunomodulation, epithelial cell growth, keratinocyte apoptosis, and antioxidant properties.
Figure 1. Average beta values across all CpGs of the top 100 DMRs
Biological Age: The study observed a slight increase in the biological age of the skin tissue, potentially due to a change in the ratio of cell differentiation and proliferation. This shift can lead to additional stress on the tissue in the short term. However, the long-term epigenetic effects of tretinoin on the skin remain to be thoroughly investigated.
Figure 2. Predicted biological age changes over 56 days. Participants were sampled every 14 days. Participant #6 overlaps with Participant #5
Cell composition: There is an indication of an increase in granulocytes and a decrease in keratinocytes with short-term tretinoin use at Day-28 and Day-56 compared to baseline (Day-0). These results correlate with the inflammation-related clinical outcomes reported by the volunteers such as increased redness and irritation. However, the result is not statistically significant (p ~ 0.17) due to the reduced number of samples in the pilot study.
Figure 3. Cell composition showing a potential increase in immune infiltrates with tretinoin short-term use over 56 days
Deeper dive in pathway changes
The differentially methylated regions (DMRs) identified in the study were involved in critical biological processes, further validating the impact of tretinoin at a molecular level. The key pathways affected included:
Monocyte Differentiation: Linked to immunomodulation, tretinoin influences monocyte activity, impacting Langerhans cells which play a role in skin immunity. (2)
Regulation of Small GTPase Mediated Signal Transduction: This pathway is crucial for epithelial cell growth and differentiation, which is essential for maintaining skin structure and function. (3)
Regulation of Keratinocyte Apoptosis: Tretinoin increases mitotic activity in keratinocytes, leading to enhanced cell turnover. (4)
Regulation of Cellular Response to Oxidative Stress: Tretinoin’s antioxidant properties help in mitigating stress-induced oxidative damage, promoting healthier skin. (5)
Conclusion
Tretinoin continues to be a potent tool in the fight against skin ageing, offering substantial benefits in improving skin appearance and texture. However, its limitations and the need for careful application underscore the importance of professional guidance. The advent of epigenetic research provides a promising avenue to further understand and optimize the use of such treatments. By examining the molecular underpinnings of tretinoin’s effects, scientists can develop more targeted and effective anti-ageing strategies.
As we move forward, larger longitudinal studies will be crucial to fully elucidate the long-term impacts of tretinoin and other retinoic acids on skin health.
References
1 Banila et al., Br J Dermatol., 2023 https://doi.org/10.1093/bjd/ljad316
2 Schmidt et al., J Clin Aesthet Dermatol., 2011, PMID: 22125655
3 Wang et al., Pharmacol Ther., 2020 https://doi.org/10.1016/j.pharmthera.2019.107415
4 Melnik et al., J Transl Med., 2017 https://doi.org/10.1186/s12967-017-1297-2
5 Romana-Souza et al., Exp Dermatol., 2019 https://doi.org/10.1111/exd.13675
Mitra Bio developed a non-invasive skin diagnostics platform capable of measuring biological skin ageing. We believe solving skin ageing could be a big boon to the field of ageing as it is a biomarker that is very visible externally.
If you are developing longevity ingredients and would like to use DNA methylation age clocks to track efficacy, we’d love to hear from you.
