Nambidi Sibin, Pallatt Sneha, Banerjee Antara, Pathak Surajit, Chan Mike K S
Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, Tamil Nadu, India.
European Wellness Biomedical Group, Klosterstrasse 205, 67480, Edenkoben, Germany.
Mol Biol Rep. 2025 May 27;52(1):507. doi: 10.1007/s11033-025-10575-3.
Klotho, named after the youngest of the three Fates in Greek mythology daughters of Zeus and Nyx, who together spin the thread of life, allot destiny, and determine the time of passing for both mortals and immortals, is an important regulatory factor in aging and cancer dynamics. Initially described as an aging-suppressing protein, Klotho is now recognized for its more diverse role in modulating key signaling pathways like Wnt/β-catenin, IGF-1, PI3K/AKT, and TGF-β. Essentially, its various pro-cellular health functions, such as antioxidant, anti-inflammatory, and tumor-suppressive activities, are, in fact, considered that ensures the maintenance of cellular health and reduce complications related to aging. Klotho deficiency is associated with accelerated aging, chronic kidney disease, cardiovascular disorders, neurodegeneration, and various cancers. This review thus covers the twin roles of Klotho as an antiaging and tumor-suppressor protein, on their therapeutic potential, as well as advances in delivery systems and development of biomarkers and challenges for clinical translation.. Moreover, natural strategies like exercise and dietary interventions are explored that could help overcome Klotho deficiency. Further research with Klotho may offer a paradigm shift in the treatment of aging and cancer and add yet another avenue to increase survival of the patients.
klotho是以希腊神话中三位命运女神中最年轻的一位命名的，她是宙斯和尼克斯的女儿，她们共同纺出生命之线、分配命运，并决定凡人和不朽者的死亡时间。klotho是衰老和癌症动态变化中的一个重要调节因子。最初被描述为一种抑制衰老的蛋白质，现在klotho因其在调节Wnt/β-连环蛋白、IGF-1、PI3K/AKT和TGF-β等关键信号通路中的更多样化作用而被认可。本质上，它的各种促进细胞健康的功能，如抗氧化、抗炎和肿瘤抑制活性，实际上被认为确保了细胞健康的维持并减少了与衰老相关的并发症。klotho缺乏与加速衰老、慢性肾病、心血管疾病、神经退行性变和各种癌症有关。因此，本综述涵盖了klotho作为一种抗衰老和肿瘤抑制蛋白的双重作用、它们的治疗潜力，以及递送系统的进展、生物标志物的开发和临床转化面临的挑战。此外，还探讨了运动和饮食干预等自然策略，这些策略可能有助于克服klotho缺乏。对klotho的进一步研究可能会在衰老和癌症的治疗方面带来范式转变，并为提高患者生存率增添另一条途径。
