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    Beyond the Hayflick limit: How microbes influence cellular aging
    (Elsevier Ireland Ltd, 2025) Abavisani, Mohammad; Faraji, Saba; Ebadpour, Negar; Karav, Sercan; Sahebkar, Amirhossein
    Cellular senescence, a complex biological process resulting in permanent cell-cycle arrest, is central to aging and age-related diseases. A key concept in understanding cellular senescence is the Hayflick Limit, which refers to the limited capacity of normal human cells to divide, after which they become senescent. Senescent cells (SC) accumulate with age, releasing pro-inflammatory and tissue-remodeling factors collectively known as the senescence-associated secretory phenotype (SASP). The causes of senescence are multifaceted, including telomere attrition, oxidative stress, and genotoxic damage, and they extend to influences from microbial sources. Research increasingly emphasizes the role of the microbiome, especially gut microbiota (GM), in modulating host senescence processes. Beneficial microbial metabolites, such as short-chain fatty acids (SCFAs), support host health by maintaining antioxidant defenses and reducing inflammation, potentially mitigating senescence onset. Conversely, pathogenic bacteria like Pseudomonas aeruginosa and Helicobacter pylori introduce factors that damage host DNA or increase ROS, accelerating senescence via pathways such as NF-?B and p53-p21. This review explores the impact of bacterial factors on cellular senescence, highlighting the role of specific bacterial toxins in promoting senescence. Additionally, it discusses how dysbiosis and the loss of beneficial microbial species further contribute to age-related cellular deterioration. Modulating the gut microbiome to delay cellular senescence opens a path toward targeted anti-aging strategies. This work underscores the need for deeper investigation into microbial influence on aging, supporting innovative interventions to manage and potentially reverse cellular senescence. © 2025 Elsevier B.V.
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    Overcoming antibiotic resistance: the potential and pitfalls of drug repurposing
    (Taylor & Francis Ltd, 2024) Abavisani, Mohammad; Khoshrou, Alireza; Eshaghian, Souzan; Karav, Sercan; Sahebkar, Amirhossein
    Since its emergence shortly after the discovery of penicillin, antibiotic resistance has escalated dramatically, posing a significant health threat and economic burden. Drug repositioning, or drug repurposing, involves identifying new therapeutic applications for existing drugs, utilising their established safety profiles and pharmacological data to swiftly provide effective treatments against resistant pathogens. Several drugs, including otilonium bromide, penfluridol, eltrombopag, ibuprofen, and ceritinib, have demonstrated potent antibacterial activity against multidrug-resistant (MDR) bacteria. These drugs can disrupt biofilms, damage bacterial membranes, and inhibit bacterial growth. The combination of repurposed drugs with conventional antibiotics can reduce the required dosage of individual drugs, mitigate side effects, and delay the development of resistance, making it a promising strategy against MDR bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Despite its promise, drug repurposing faces challenges such as potential off-target effects, toxicity, and regulatory and intellectual property issues, necessitating rigorous evaluations and strategic solutions. This article aims to explore the potential of drug repurposing as a strategy to combat antibiotic resistance, examining its benefits, challenges, and future prospects. We address the legal, economic, and practical challenges associated with repurposing existing drugs, highlight successful examples, and propose solutions to enhance the efficacy and viability of this approach in combating MDR bacterial infections.