Senolytics: Can Their Impact on Senescent Cells Be the Longevity Answer Everyone is Looking for?

Senolytics: Can Their Impact on Senescent Cells Be the Longevity Answer Everyone Is Looking for?

Aging is an intricate process influenced by various factors, both intrinsic and extrinsic. Among the underlying mechanisms that contribute to aging, senescent cells have emerged as significant players. These cells, characterized by irreversible growth arrest, accumulate in tissues over time and have implications for age-related ailments. This article aims to delve deep into the world of senescent cells, exploring their impact on the aging process and specifically focusing on their role in overall health and skin health.

Understanding Senescent Cells:

Senescent cells, also known as senescent or aging cells, are a result of cellular damage or stress. When cells encounter irreparable DNA damage, telomere attrition, or other harmful stimuli, they enter a state of irreversible cell cycle arrest. Senescence serves as a protective mechanism to prevent the replication of damaged cells, reducing the risk of cancerous growth. However, the accumulation of senescent cells over time can have detrimental effects on tissue function.

The Role of Senescent Cells in Aging:

Senescent cells actively contribute to the aging process through various mechanisms. One of the key factors is their secretion of pro-inflammatory molecules and bioactive molecules collectively known as the senescence-associated secretory phenotype (SASP). SASP components include cytokines, growth factors, and proteases that can induce inflammation and disrupt tissue homeostasis. This chronic low-grade inflammation, known as inflammaging, can negatively impact organ function and contribute to age-related diseases.

Skin Aging and Senescent Cells:

The skin is the largest organ of the body and undergoes significant changes as we age. Senescent cells play a critical role in skin aging by affecting its structure, function, and appearance. As senescent cells accumulate in the skin, they secrete SASP factors that promote inflammation and impair the regenerative capacity of skin cells. This leads to the loss of elasticity, reduced collagen production, thinning of the skin, and the formation of wrinkles and age spots.

Furthermore, senescent cells in the skin can disrupt the balance between cell proliferation and cell death. Normally, cellular turnover ensures the replacement of old cells with new ones. However, the presence of senescent cells hinders this process, leading to the persistence of damaged cells and a compromised barrier function. Consequently, the skin becomes more susceptible to environmental insults, such as UV radiation and oxidative stress.

Senolytics and Skin Health:

The discovery of senolytics, compounds that selectively target and eliminate senescent cells, has opened new avenues for potential anti-aging interventions. Senolytic agents, such as quercetin and fisetin, have shown promising results in preclinical studies by clearing senescent cells and improving tissue function.

In the context of skin health, senolytics offer a novel approach to combat skin aging. By selectively removing senescent cells from the skin, these compounds could rejuvenate the tissue, restore its regenerative capacity, and enhance its barrier function. This could translate into improved skin elasticity, reduced wrinkles, and a more youthful appearance.

Challenges and Future Directions:

Despite the exciting prospects of senolytics, several challenges need to be addressed. Developing effective and safe senolytic agents, understanding their optimal dosages and timing, and identifying potential side effects are key areas of ongoing research. Furthermore, since senescence is a complex phenomenon, targeting senescent cells alone may not be sufficient to fully address the intricacies of aging. Combination therapies and a comprehensive understanding of the interplay between different aging mechanisms will likely be essential for optimal outcomes.

Are there Natural Compounds with Senolytic Properties?

While senolytics are primarily being developed as synthetic drugs, there are certain natural compounds that have been investigated for their potential senolytic properties. Some examples include:

1. Quercetin: Quercetin is a flavonoid found in various fruits and vegetables, such as apples, onions, and berries. It has been studied for its senolytic effects and has shown the ability to induce selective apoptosis (programmed cell death) in senescent cells.

2. Fisetin: Fisetin is another flavonoid found in fruits and vegetables, including strawberries, apples, and cucumbers. Similar to quercetin, fisetin has demonstrated senolytic properties by promoting the elimination of senescent cells through apoptosis.

3. Resveratrol: Resveratrol is a natural compound found in grapes, red wine, and certain berries. It has been investigated for its potential anti-aging effects, including its ability to target senescent cells and improve overall healthspan.

4. Curcumin: Curcumin is a bioactive compound derived from turmeric. It has been studied for its diverse health benefits, including its potential senolytic properties. Curcumin has shown the ability to induce apoptosis in senescent cells and alleviate age-related dysfunctions.

5. Green tea extract: Green tea contains polyphenols, such as epigallocatechin gallate (EGCG), which have been investigated for their potential senolytic effects. Green tea extract has shown promising results in selectively eliminating senescent cells and enhancing cellular function.

It's worth noting that while these natural compounds have shown senolytic properties in experimental studies, their effectiveness and safety in humans are still areas of ongoing research. It's important to consult with healthcare professionals before considering the use of any natural products or supplements for their potential senolytic effects.

The Research on Senolytics

In a notable 2020 study, researchers J.L. Kirkland and T. Tchkonia explored the development and potential translation of senolytic drugs, which selectively clear senescent cells (SC) from the body. SC accumulate with aging and are implicated in various chronic disorders that contribute to morbidity, mortality, and healthcare costs.

The initial senolytic drugs, including Dasatinib, Quercetin, Fisetin, and Navitoclax, were discovered through a hypothesis-driven approach. These drugs target the anti-apoptotic pathways that protect senescent cells, making them resistant to apoptosis. By disabling these pathways, senolytics induce apoptosis in the most harmful senescent cells with a tissue-destructive SASP (senescence-associated secretory phenotype).

Animal studies have shown promising results, as senolytics have delayed, prevented, or alleviated a wide range of age-related disorders, including frailty, cancers, cardiovascular diseases, neurodegenerative conditions, and skin disorders.

Early pilot trials in humans have demonstrated a reduction in senescent cells, decreased inflammation, and improved frailty. Ongoing clinical trials are investigating the potential of senolytics in various conditions such as diabetes, Alzheimer's disease, COVID-19, and osteoarthritis. However, until further studies are completed, the use of senolytics outside of clinical trials should be approached with caution.

The Future is here, According to the Mayo Clinic

Patents on senolytic drugs are already held by Mayo Clinic, and products are starting to make their way to the market. One that caught my attention is Neurohacker Collective's Qualia Senolytic. A company owned by some of the leading minds in science, entrepreneurs and wellness experts. Some notable names are; Dave Asprey, Susan Bratton (best-selling author), Thaddeus Owen (of Primal Hacker), Mike Bledsoe (of Bledsoe Show), Anti and Arlene Fletcher, Dr. Heather Sandison, Mark Divine (of Sealfit), Jason Silva (of Brain Games), Brian Mackenzie (creator of Crossfit), and many more...

The revolutionary product, Qualia Senolytic, is the result of extensive research dedicated to understanding the biological processes of aging. This groundbreaking two-day rejuvenation regimen has the potential to unlock cellular health and revitalize aging tissues throughout the body, offering a new approach to combating the effects of aging.

 Ingredient Breakdown of Qualia Senolytic

Let's explore the ingredients and their functions in Qualia Senolytic:

1. Fisetin (from Rhus succedanea Stem Extract): This ingredient supports tissue health by assisting in the removal of stressed cells, promoting a more vibrant and rejuvenated cellular environment.

2. Quercefit® Quercetin Phytosome (Sophora japonica L. Flower Extract / Phospholipid Complex from Sunflower): By aiding in the removal of stressed cells, this ingredient also contributes to tissue health, supporting overall rejuvenation.

3. Longvida Optimized Curcumin® Extract (from Curcuma longa Root): This ingredient specifically targets brain health and cognitive function, helping to support optimal brain performance.

4. Olive Leaf Extract: With its focus on joint health, this extract helps manage stressed cells in the joints, promoting overall joint well-being.

5. Soybean Seed Extract: By supporting healthy cellular functions involved in managing stressed cells, this extract contributes to maintaining cellular health and vitality.

6. Luteolin (from Sophora japonica L. Flower Extract): Similar to other ingredients, luteolin plays a role in supporting tissue health by assisting in the removal of stressed cells.

7. Milk Thistle Seed Extract: This extract is dedicated to supporting liver health and aiding in the management of stressed cells, ensuring optimal liver function.

8. Piperlongumine (from Piper longum Root Extract): With its senolytic and immune-supporting properties, this ingredient helps manage stressed cells, supporting overall cellular health.

9. Senactiv® (Panax notoginseng Root Extract and Rosa roxburghii Fruit Extract): This unique blend supports exercise recovery and assists in managing senescent cells in muscle tissue, promoting optimal muscle function and vitality.

These ingredients work together synergistically to provide comprehensive support for cellular health, tissue rejuvenation, brain function, joint health, liver health, and muscle vitality. 

Conclusion:

Senescent cells significantly contribute to the aging process, and their impact on skin health is particularly noteworthy. The accumulation of senescent cells in the skin disrupts its structure and function, leading to visible signs of aging. Senolytic agents offer a promising avenue to counteract these effects by selectively eliminating senescent cells and rejuvenating the skin.

Reference:

https://pubmed.ncbi.nlm.nih.gov/32686219/

https://neurohacker.com