Introduction
Considering the increase in the elderly population and aging-related disorders, there is a need for strategies to reduce the complications of aging. Senolytic agents are a group of different drugs that improve the function of tissues and organs in elderly people by selective elimination of aging cells, mainly by inducing apoptosis in cells with senescent phenotype [2]. These drugs have been developed for therapeutic purposes other than senolysis; however, in many laboratory, experimental, and clinical studies, senolytic properties have been observed in them. In this review article, a summary of the mechanisms of cellular aging and the selective effect of senolytic agents on these cells, as well as different categories of senolytic drugs and therapeutic strategies with senolytic effect, the results of their administration, and the progress made in this field have been provided.

Methods & Materials 
According to the publication of the first articles about senolytics in 2015, all of the articles with the keywords “senolysis” or “senolytics” in title or abstract published between 2015 and 2023 were searched in PubMed, Scopus, and Google Scholar search engines. Subsequently, 108 out of 121 articles, which were in English and open access, were downloaded and assessed. After studying the articles and validating them, repetitive articles, review articles about a specific disorder, editorials, case reports, and articles published in non-indexed journals and congress booklets were omitted (considering the PRISMA Checklist of systematic review articles). As a result, 50 articles remained, and a summary of their findings was provided as a review article.

Results
Currently, 12 categories of senolytic agents have been identified, and their therapeutic effects in amelioration of aging complications are under study [6]. The first category is kinase inhibitors, from which dasatinib has shown the most anti-senescence effects. The second category is natural polyphenols, including quercetin, which is the main flavonoid found in vegetables and fruits. The combination of dasatinib and quercetin has shown the most efficacy in reducing the effects of aging. Various anti-cancer drugs and those that induce apoptosis in cells, including Bcl2 protein family inhibitors and P53 stabilizers, are the other categories of senolytic drugs. Navitoclax and UBX0101 are the most studied drugs in these two categories, respectively, which have caused a decrease in the number of senescent cells in joint and liver tissues of the experimental models. 
The next groups include heat shock protein inhibitors and inhibitors of the BET protein family, which have been investigated for their anti-inflammatory and anti-cancer effects in vitro as well as in preclinical studies. Administration of these drugs resulted in the apoptosis of cells with aging phenotype in human and experimental models. 
Cardiac steroids are mainly used in the treatment of heart failure; however, digoxin and ouabain were effective in the selective elimination of aged fibroblasts and apoptosis of senescent liver cells. PPARα agonists, such as fenofibrate, have also shown therapeutic effects in osteoarthritis and cartilage degeneration. In addition, antibiotics, such as azithromycin and roxithromycin, have been able to eliminate senescent fibroblasts in laboratory studies, but studies on the senolytic effects of other antibiotics are ongoing. Moreover, integrase inhibitors classified as antiviral drugs induced apoptosis in old T lymphocytes and may be used as senolytic agents [7].
The other strategy that has been proposed to remove old cells is calorie restriction. Fasting and calorie restriction have already shown positive effects in rejuvenating tissues and increasing life span. This alternative has significantly induced younger genetic profiles in human and animal studies [48]. Furthermore, novel therapeutic approaches, such as chimeric antigen receptor (CAR-T) cell therapy, have the potential to selectively eliminate aged cells that express senescence markers. These strategies are being studied in various phases of preclinical or clinical research (Table 1) [9].





Conclusion
Considering the increasing trend in the elderly population, one of the solutions to deal with debilitating complications of old age is senolytic drugs, which can eliminate senescent cells with unfavorable function. The main categories of senolytics with the most promising results are kinase inhibitors and natural polyphenols; however, new strategies, such as specific targeting of senescent cells using CAR-T cells technology, are also under study. Although in various research models, senolytics have shown efficacy in reducing the complications of aging, a standard treatment regimen has not yet been established, and studies are still ongoing. If the effectiveness and safety of these drugs in removing senescent cells are confirmed, there will be the possibility of providing a healthier and more dynamic aging for the elderly population in the future.

Ethical Considerations
Compliance with ethical guidelines
All ethical principles were considered in this article. The participants were informed about the purpose of the research and its implementation stages; they were also assured about the confidentiality of their information; Moreover, They were allowed to leave the study whenever they wish, and if desired, the results of the research would be available to them.

Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions
Drafting the manuscript: Sara Assadiasl; Search and data collection: Sepehr Safdel; Revision and edition of the manuscript: Mohammad Hossein Nicknam

Conflicts of interest
The authors declared no conflict of interest.


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