The field of longevity research continues to evolve as our understanding of the ageing process deepens. A promising class of compounds is gaining attention in the industry for its potential role in promoting lifespan and healthy ageing: senolytic drugs. These compounds aim to target and selectively eliminate senescent cells, thus holding the potential to mitigate age-related conditions and improve tissue function.
Understanding senescence
Senescence is a fundamental biological process where cells halt division and enter a dormant state characterized by gradual deterioration over time. While this mechanism serves as a protective measure against cells that have the potential to become cancerous, the buildup of senescent cells is linked to ageing and age-related conditions. Senescent cells undergo various structural and functional changes and often release a complex mixture of signaling molecules, known as the senescence-associated secretory phenotype (SASP), which can contribute to inflammation and tissue dysfunction.
Promising Senolytic Drugs
Rapamycin: Primarily known as an immunosuppressant, the senolytic properties of Rapamycin have been investigated in the context of age-related diseases. Data obtained from clinical trials showed that topical rapamycin reduced cellular senescence and relatively improved skin clinical appearance and histological markers of ageing.
Dasatinib and Quercetin (D+Q): the first senolytic drugs to be identified in 2015. Research has indicated a reduction in senescent cell burden and improvements in skin elasticity, which suggest that senolytic drugs could indeed be a game-changer in the fight against skin ageing.
Navitoclax: Although originally developed as a cancer treatment, research has indicated its potential to reduce senescent cells and alleviate age-related tissue dysfunction, potentially benefiting the skin. This study determined that using Navitoclax can improve the ageing phenotype of human skin without side effects, thus marking it as a potential therapeutic agent for skin ageing.
Impact on skin ageing
The largest organ in the human body, skin, is affected not only by intrinsic, but also extrinsic stimuli. Intrinsic (chronological) ageing is influenced by genetic factors and largely predetermined by an individual’s makeup. However, extrinsic ageing is primarily caused by external and environmental factors, such as ultraviolet (UV) rays and air pollution, but can also be accelerated by lifestyle habits, such as smoking, poor nutrition, or inadequate skin care.
- Improved Collagen Production: Senolytic drugs may stimulate the production of collagen, a protein crucial for maintaining skin elasticity and firmness. By eliminating senescent cells, these drugs could potentially promote collagen synthesis and reduce the appearance of wrinkles.
- Reduced Inflammation: The elimination of senescent cells may lead to a reduction in inflammation associated with the SASP. Inflammation is a key contributor to skin ageing, and senolytics could help mitigate this process, promoting healthier skin.
- Enhanced Skin Regeneration: Senolytic drugs may support the skin’s natural regenerative processes by removing obstacles to cellular turnover. This could lead to improved skin texture and a more youthful appearance.
Challenges and Future Directions
While the potential of senolytic drugs is undeniable, there still are challenges to address. Researchers are working on optimising the specificity of senolytic compounds to minimise off-target effects and exploring novel delivery methods. Additionally, long-term safety & efficacy data as well as properly designed clinical trials are essential for adopting senolytic drugs as a viable anti-ageing strategy.
Partial Cellular Reprogramming
As the fascination with skin ageing grows, various avenues of research are explored. One such method capturing attention is partial cellular reprogramming, which represents a process in which specific genes are activated to reverse the epigenetic ageing of cells without fully converting them into pluripotent stem cells. In partial cellular reprogramming, the goal is to activate a set of genes, often referred to as “Yamanaka factors” (transcription factors), for a limited time to reverse epigenetic ageing without altering the cell’s identity. Although still early in clinical development, this method holds promising potential as a futuristic avenue for aesthetic applications in the beauty industry. By leveraging skin-based epigenetic clocks as surrogate biomarkers, these therapies could be validated in their attempt to reverse the ageing process, on the human skin, not just in the models, potentially offering rejuvenation benefits for skin health. While the research is still in its early stages, numerous start-ups and major corporations are actively engaged in advancing these innovative approaches. The future of the industry is looking more and more exciting!
Mitra Bio is building a non-invasive skin diagnostics platform capable of measuring 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.
At the moment biopsies are necessary to get good skin ageing measurements which makes clinical trials expensive and hard to recruit for.
With cheaper/easier skin ageing diagnostics, we will start to see better data around the efficacy of potential anti-ageing dermatological treatments which may help both accelerate the development of such therapies and improve adoption once therapies are developed.
