Inflammation and Senolytics

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      Inflammation plays a crucial role in our body's defense mechanism against harmful stimuli, such as pathogens and injuries. However, when inflammation becomes chronic and unresolved, it can contribute to various age-related diseases, including arthritis, cardiovascular diseases, neurodegenerative disorders, and cancer. Recent advancements in medical research have identified a promising solution to combat inflammation and its associated health issues: senolytics. In this blog post, we will explore the fascinating world of senolytics, understand how they work for cellular senescence, and delve into the benefits they offer in combating age-related diseases.

      What are Senolytics?

      Senolytics are a class of drugs that specifically target and eliminate senescent cells in our bodies. Senescence refers to a state where cells lose their ability to divide and function optimally. These senescent cells accumulate with age and secrete harmful substances that contribute to chronic inflammation and tissue damage. Senolytics work by selectively inducing apoptosis (programmed cell death) in senescent cells, thereby clearing them from the body.

      What Is Cellular Senescence?

      Cellular senescence is a process in which cells stop dividing and exhibit distinct phenotypic changes. Hayflick and Moorhead coined the term “cellular senescence” for the first time in 1961. They described the phenomenon as an irreversible growth arrest of a human diploid cell(containing two complete sets of chromosomes, one from each parent) which remained metabolically active after a prolonged time in culture.

      Cellular senescence can be triggered in normal cells in response to a wide range of stress-inducing factors. These factors include both external and internal damaging events like abnormal cellular growth, oxidative stress, DNA damage, reactive metabolites, and toxins.

      During normal development, cellular senescence restricts the uncontrolled growth of aged and damaged cells. However, it is also associated with ageing and induces age-related pathologies.

      Normally, our body effectively removes senescent cells, making a place for new, healthy cells. However, as we get older, our body produces more senescent cells; at the same time, mechanisms for getting rid of the extra senescent cells become less efficient. Consequently, our tissues experience a net buildup of senescent cells. This contributes to many age-associated conditions, including cancer, tissue degeneration, and inflammation.

      How do Senolytics work for Cellular Senescence?

      To understand how senolytics work, let's take a closer look at cellular senescence. Senescence is a natural process that occurs in response to various stressors, including DNA damage, oxidative stress, and telomere shortening. When cells undergo senescence, they lose their ability to divide and enter a state of permanent growth arrest. While this can be beneficial in preventing the proliferation of damaged cells, it also leads to the accumulation of senescent cells over time.

      Senescent cells secrete a range of bioactive molecules collectively known as the senescence-associated secretory phenotype (SASP). The SASP includes inflammatory cytokines, growth factors, and proteases that can disrupt tissue homeostasis and promote chronic inflammation. Senolytics counteract these effects by selectively targeting senescent cells and triggering their elimination through apoptosis. By clearing senescent cells, senolytics help restore tissue function and alleviate chronic inflammation.

      The Benefits of Senolytics

      The potential benefits of senolytics extend far beyond their role in combating inflammation. Research studies have shown that senolytics have a positive impact on various age-related diseases and promote overall health and longevity. Here are some notable benefits of senolytics:

      Delaying Aging: Senolytics have been found to slow down the aging process in animal models. By removing senescent cells, senolytics help rejuvenate tissues, improve organ function, and extend lifespan.

      Alleviating Age-Related Diseases: Senescent cells are strongly associated with age-related diseases, including osteoarthritis, cardiovascular diseases, neurodegenerative disorders (such as Alzheimer's and Parkinson's), and cancer. Senolytics have shown promising results in reducing disease burden and improving overall health outcomes in preclinical studies.

      Enhancing Tissue Regeneration: Senolytics promote tissue regeneration by clearing senescent cells that hinder the healing process. This can be particularly beneficial in wound healing, bone repair, and other regenerative medicine applications.

      Improving Metabolic Health: Chronic inflammation and cellular senescence contribute to metabolic disorders, such as diabetes and obesity. Senolytics have demonstrated the potential to improve metabolic health by reducing inflammation and restoring metabolic balance.

      What Is Cellular Inflammation?

      Cellular inflammation is a double-edged sword; it functions as an important immune response against pathogenic disturbances and maintains biological stability. However, inflammation can also occur due to ageing-associated accumulation of senescent cells.

      Senescent cells secrete proinflammatory substances, which create a micro environment of “chronic low-grade inflammation”, also known as “inflammaging”. This phenomenon persists both in tissues and organs and is a hallmark of most ageing-related diseases.

      Unfortunately, this inflammation does not stop with a single cell. Senescent cells act similarly to neighboring cells as a rotten apple in a basket does to neighboring apples. The released proinflammatory substances attack healthy cells and transform them into senescent cells. Due to this, senescent cells are also called zombie cells.

      The situation worsens as senescent cells secrete substances that allow immune cells into senescence, thereby reducing the number of immune cells available to fight pathogens and other damaging stimuli.

      Inflammation and Age-Related Diseases

      Chronic inflammation plays a significant role in the development and progression of age-related diseases. As we age, our immune system undergoes changes, leading to a chronic state of inflammation known as inflammaging. This persistent low-grade inflammation contributes to the pathogenesis of many age-related conditions.

      Inflammation and cellular senescence create a vicious cycle. Senescent cells secrete inflammatory molecules, which, in turn, promote the accumulation of more senescent cells. This cycle perpetuates chronic inflammation and accelerates the aging process.

      By targeting senescent cells and reducing chronic inflammation, senolytics offer a promising approach to combat age-related diseases. They have the potential to improve the quality of life for individuals suffering from arthritis, cardiovascular diseases, neurodegenerative disorders, and even cancer.

      Senolytics as an Anti-Inflammation Agent

      Eliminating senescent cells and preventing the accumulation of senescent cells is an effective way of slowing ageing and age-related diseases.

      The elimination of senescent cells is done perfectly by senolytics, a class of small molecules that can selectively induce death in senescent cells and improve health in humans. Senolytics promote self-destruction in senescent cells, thus reducing chronic inflammation and enhancing tissue regeneration. Senolytics are considered to be a viable treatment for some aspects of ageing and may even promote healthy longevity.

      How Senolytics Promote Longevity

      Senolytics hold immense potential in promoting longevity by targeting and removing senescent cells. By eliminating these dysfunctional cells, senolytics help to restore tissue homeostasis and improve overall health.

      The mechanism of action of senolytics involves selectively triggering apoptosis in senescent cells. This is achieved through various pathways, including the activation of pro-apoptotic proteins and interfering with the signaling pathways that enable senescent cells to evade cell death.

      Studies in animal models have demonstrated that senolytics can delay or alleviate age-related diseases, improve physical function, and extend lifespan. These findings have sparked considerable excitement in the scientific community, leading to further research on the potential benefits of senolytics in humans.

      Senolytics and Healthspan

      While lifespan refers to the length of time an organism lives, healthspan focuses on the period of life spent in good health, free from age-related diseases and disabilities. Senolytics have the potential to extend healthspan by targeting the underlying cellular processes associated with aging.

      By removing senescent cells, senolytics have shown promising results in mitigating age-related conditions such as osteoporosis, cardiovascular disease, neurodegenerative disorders, and even certain types of cancers. These interventions have the potential to improve the quality of life for aging individuals, enabling them to maintain their vitality and independence for longer periods.

      Current Research and Future Potential

      The field of senolytics is rapidly evolving, with ongoing research aimed at optimizing their effectiveness and safety. Various senolytic compounds are being studied, including dasatinib, quercetin, navitoclax, and fisetin, among others. Researchers are exploring different administration methods, dosage regimens, and combinations of senolytics to maximize their benefits.

      Furthermore, efforts are being made to develop senolytics that are more selective in targeting senescent cells, minimizing potential side effects on healthy tissues. The aim is to strike a delicate balance between removing harmful senescent cells and preserving the function of healthy cells.

      While the full potential of senolytics in humans is yet to be realized, the emerging evidence suggests a promising future. As research progresses, we may witness the development of innovative therapies that can revolutionize the way we approach aging and age-related diseases.

      Bottom Line

      Ageing and many age-associated chronic diseases that account for the majority of deaths, morbidity, and medical costs in contemporary society could be linked to chronic inflammation, cellular senescence, or other fundamental ageing mechanisms.

      Senolytic compounds such as Dasatinib, Fisetin and Quercetin are the most popular drugs for killing senescent cells. This is backed by several studies which demonstrate that the senolytic treatment reduces cellular senescence and inflammation.

       

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