Abstract:
Multiple changes occur in hormonal regulation with aging and across various endocrine organs. These changes are associated with multiple age-related disorders and diseases. A better understanding of responsible underling biological mechanisms could help in the management of multiple endocrine disorders over and above hormone replacement therapy (HRT). Cellular senescence is involved in multiple biological aging processes and pathologies common in elderly individuals. Cellular senescence, which occurs in many older individuals but also across the lifespan in association with tissue damage, acute and chronic diseases, certain drugs, and genetic syndromes, may contribute to such endocrine disorders as osteoporosis, metabolic syndrome, and type II diabetes mellitus (T2DM). Drugs that selectively induce senescent cell removal, \"senolytics\", and drugs that attenuate the tissue-destructive secretory state of certain senescent cells, \"senomorphics\", appear to delay the onset or alleviate multiple diseases, including but not limited to endocrine disorders such as diabetes, complications of obesity, age-related osteoporosis, and cancers as well as atherosclerosis, chronic kidney disease, neurodegenerative disorders, and many others. Over thirty clinical trials of senolytic and senomorphic agents have already been completed, are underway, or are planned for a variety of indications. Targeting senescent cells is a novel strategy that is distinct from conventional therapies such as HRT, and thus might address unmet medical needs and can potentially amplify effects of established endocrine drug regimens, perhaps allowing for dose decreases and reducing side effects.
摘要:
随着衰老和各种内分泌器官的激素调节发生多种变化。这些变化与多种年龄相关的病症和疾病相关。更好地了解负责任的基础生物学机制可能有助于治疗激素替代疗法(HRT)以外的多种内分泌疾病。细胞衰老涉及老年个体中常见的多种生物衰老过程和病理。细胞衰老,这发生在许多老年人身上,也发生在与组织损伤相关的整个生命周期中,急性和慢性疾病,某些药物,和遗传综合症,可能会导致骨质疏松症等内分泌紊乱,代谢综合征,和II型糖尿病(T2DM)。选择性诱导衰老细胞去除的药物,\"senoletics\",以及减弱某些衰老细胞的组织破坏性分泌状态的药物,“感官形态”,似乎延迟发病或缓解多种疾病,包括但不限于内分泌失调,如糖尿病,肥胖的并发症,与年龄有关的骨质疏松症,癌症和动脉粥样硬化,慢性肾病,神经退行性疾病,和许多其他人。已经完成了30多项抗衰老剂和衰老剂的临床试验,正在进行中,或计划用于各种适应症。靶向衰老细胞是一种不同于传统疗法如HRT的新策略。因此可能解决未满足的医疗需求,并可能扩大已建立的内分泌药物方案的影响,也许允许剂量减少和减少副作用。