Is it possible to stop aging? It’s a million-dollar question, indeed. But no, aging cannot be stopped because it is a complicated mixture of degenerative diseases whose underlying biological process is unclear.
However, pharmacological treatments can temporarily halt the aging process by preventing its causes. Consequently, the main objective of current research is to extend the ‘healthspan,’ or the number of years a person can expect to live with no serious health problems.
For this, another class of drugs has been studied, known as Senotherpauetics.
It is the medical terminology for developing strategies to target cellular senescence, which in turn has beneficial effects on aging and age-related changes. They provide proof that suggests that cellular senescence can be delayed, which is viewed favorably.
Nearly 30 clinical studies are currently examining the function of senotherapeutics in the treatment of diverse malignancies, aging phenotypes, neurodegenerative diseases, and infections. But now the question arises, what are senescent cells that cause such problems?
What are Senescent cells?
The cells that have ceased proliferating and are no longer carrying out their normal functions, such as cease reproduction, yet do not die when they should, are called senescent cells. Accumulating evidence suggests that these cells have a role in the development of a number of age-related illnesses and disorders.
Damage and inflammation accrued over a lifetime cause younger cells to senesce, a process that ultimately contributes to the aging process. In conclusion, this leads to cellular senescence, which is characterized by cells losing their capacity for renewal and response. Senescent cells accumulate in the body over time, contributing to the extremely unusual declines in health and metabolism that come with old age.
It is believed that an accumulation of senescent cells speeds up the aging process and raises the chance of age-related diseases such as (1)(2),
- Diabetes,
- Obesity,
- Stroke,
- Vision loss,
- Neurodegenerative disorders,
- Osteoarthritis,
- Emphysema, and
- Cancer.
Inflammation is produced at a higher rate by senescent cells than by healthy ones, and this is known to promote the aging process. In contrast to younger cells, they do not react to or generate the same levels of hormones or neurotransmitters. The senescent cells do not proliferate and show resistance to both apoptosis (programmed cell death) and tissue healing (autophagy).
Cellular senescence is one of the hallmarks of the aging and buildup of cellular senescence, and age-related diseases have been linked together in the background.
Senolytic and senomorphic agents are two kinds of novel treatments being created to alleviate the aging process. These anti-aging drugs are cutting-edge because they target senescent cells in many ways. Even in animal studies, senotherapeutics have been shown to decrease the number of senescent cells, which in turn increases lifespan and decreases the probability of getting age-related illnesses.
https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16350
With so many other compounds in development, senotherapuetics holds great promise.
Senolytics.
The prefix “sen” refers to old age, while the suffix “lytic” indicates destructive potential, hence the name “senolytic.”
They are effective in reducing inflammation and improving tissue function in the elderly by hastening the elimination of senescent cells by forcing apoptosis in senescent cells. New, more renewable cells that generate less inflammation emerge when senescent cells are permitted to die off.
By decreasing the number of senescent cells and consequently delaying the aging process, senolytic compounds are a promising anti-aging strategy with significant therapeutic potential. Their potential as chemotherapeutic adjuvants is also of considerable interest.
Better results are seen when these chemicals are used in conjunction with senomorphic, which delays aging by blocking the activity of senescent cells.
The natural senolytics present in nutrient-dense foods are responsible for many of the anti-aging advantages associated with eating a nutritious diet. Both organic and synthetic versions of these substances are being researched for potential anti-aging and regenerative medical applications.
Dasatinib, quercetin, and fisetin are a few examples of compounds that have been studied for their potential as senolytics. Some evidence-based knowledge is as below,
- Dasatinib: Apoptosis in senescent cells can be induced by the chemotherapy medication dasatinib and a senolytic drug, which works especially well in conjunction with the antioxidant quercetin (a natural senolytic). It has the ability to act on numerous receptors in senescent cells but only inhibits tyrosine kinase selectively.
When given to individuals with diabetic renal disease and idiopathic pulmonary disease, senolytics dasatinib and quercetin showed amazing results in lowering the transcript of the chosen biomarker for senescence, p16 (Ink4a).
Preadipocytes, endothelium cells, fibroblasts, and bone marrow stem cells have all responded favorably to dasatinib and quercetin. Several age-related disorders are presently being tested in phase I and II clinical trials.
- Cardiac Glycosides: These are the drugs traditionally used to treat heart problems and were later discovered to have powerful senolytic properties.
- Fisetin: It is a powerful antioxidant flavonoid that is one of the most important natural senolytics, and it is the most potent synolytic to date, as per research. Autophagy (the body’s process for cleaning out toxins in cells) is activated by fisetin because it is thought to be a potent calorie restriction mimetic.
- Quercetin: Quercetin has been shown to have substantial senolytic benefits, according to studies. The anti-aging effects of quercetin have been studied in vitro and in vivo with promising results. (1)(2)
- Epigallocatechin gallate (EGCG): It has been shown that the green tea tannin epigallocatechin gallate (EGCG) reduces the number of senescent fibroblasts in skin and chondrocytes in cartilage. It was found that EGCG inhibited p53 binding, SASP factors, and anti-apoptotic factors in preadipocytes while also suppressing aging.
Senomorphics
In order to eliminate senescent cells, senolytics function as killers, while senomorphics only attack the negative or detrimental effects of senescence only. They do it by reducing the senescent secretory inflammatory phenotype. Even though senescent cells don’t die, and they might no longer cause damage to the body.
All types of senescent inflammation and neuroendocrine activity, collectively referred to as SASP (Senescence-Associated Secretory Phenotype) are suppressed by senomorphic agents. Thus, many senomorphics have medicinal uses as antioxidants, anti-inflammatories, hormone therapies, and neurotransmitter regulators.
In other words, they are referred to as substances that simulate senolytic effects without really triggering cell death. Some of the advantages of senolytics may be shared by these substances, although they may have fewer negative effects.
Metformin and rapamycin are two such compounds.
- Metformin: As an anti-diabetic medication, metformin enjoys widespread use, but now, it’s taking a new rise as a senomorphic drug. Inhibiting inflammation, oxidative stress, cellular senescence, and cell mortality, it extends the life of animals and improves their overall health. Metformin’s impact on metabolic genes, collagen, and mitochondrial genes in adipose tissue, and DNA-repair genes in muscle indicates it may decrease the occurrence of age-related diseases in humans, including cardiovascular disease and cancer.
- Rapamycin: Mainly, the drug is famous for its immunosuppressive function. “The Hallmarks of Aging,” a 2013 analysis, is a seminal aging work. It has been shown that all of them are impacted by rapamycin.
Natural and synthetic senotherapuetic agents. Image source: https://www.frontiersin.org/files/Articles/958563/fnut-09-958563-HTML/image_m/fnut-09-958563-t002.jpg
More studies on senolytics and senomorphics are now being conducted in the field of aging and age-related disorders, with the anticipation that these substances can be applied to enhance the health and lifespan of the elderly.
What Is More Beneficial?
There are three primary grounds to believe that the effects of senolytic drugs are more promising than those of senomorphic drugs.
- By eliminating senescent cells, senolytics can be administered only when necessary, whereas to prevent the inflammatory effect, senomorphic components must be administered continuously.
- Second, senolytics eliminate the possibility of senescent bypass. Senescent cells can flee their condition through mutation, which is typically malignant as a result.
- Finally, there is no conclusive evidence that reducing SASP production would have a beneficial effect on longevity and age-related diseases.
It has been found that short senotherapeutic interventions are more successful than long-term treatment plans in slowing the onset and acceleration of senescence.
Boosting your health and making it simpler to get rid of these “zombie” cells is possible with the aid of these easy recommendations. Other methods that can help with reducing such cells are prioritizing getting enough sleep, eating a healthy, balanced diet, and exercising frequently.
The research shows that the effectiveness of senotherapy can be improved by combining senolytics and senomorphic drugs. The future of this field of study is focused on determining the selectivity, efficacy, and safety of these drugs. Overall, the health and fiscal effects of senotherapeutic drugs are extremely promising.
