Biomedical Sciences Department, School of Medicine, Creighton University, Omaha, NE 68178, USA.
Int J Mol Sci. 2024 Sep 7;25(17):9705. doi: 10.3390/ijms25179705.
Aging, a complex process marked by molecular and cellular changes, inevitably influences tissue and organ homeostasis and leads to an increased onset or progression of many chronic diseases and conditions, one of which is age-related hearing loss (ARHL). ARHL, known as presbycusis, is characterized by the gradual and irreversible decline in auditory sensitivity, accompanied by the loss of auditory sensory cells and neurons, and the decline in auditory processing abilities associated with aging. The extended human lifespan achieved by modern medicine simultaneously exposes a rising prevalence of age-related conditions, with ARHL being one of the most significant. While our understanding of the molecular basis for aging has increased over the past three decades, a further understanding of the interrelationship between the key pathways controlling the aging process and the development of ARHL is needed to identify novel targets for the treatment of AHRL. The dysregulation of molecular pathways (AMPK, mTOR, insulin/IGF-1, and sirtuins) and cellular pathways (senescence, autophagy, and oxidative stress) have been shown to contribute to ARHL. However, the mechanistic basis for these pathways in the initiation and progression of ARHL needs to be clarified. Therefore, understanding how longevity pathways are associated with ARHL will directly influence the development of therapeutic strategies to treat or prevent ARHL. This review explores our current understanding of the molecular and cellular mechanisms of aging and hearing loss and their potential to provide new approaches for early diagnosis, prevention, and treatment of ARHL.
衰老是一个由分子和细胞变化标记的复杂过程，不可避免地影响组织和器官的动态平衡，并导致许多慢性疾病和病症的发生率或进展增加，其中之一就是与年龄相关的听力损失（ARHL）。ARHL 又称老年性聋，其特征是听觉敏感性逐渐且不可逆转地下降，伴随着听觉感觉细胞和神经元的丧失，以及与衰老相关的听觉处理能力下降。现代医学延长了人类的寿命，同时也使与年龄相关的疾病的患病率上升，ARHL 就是其中之一。尽管我们在过去三十年中对衰老的分子基础有了更多的了解，但需要进一步了解控制衰老过程的关键途径与 ARHL 发展之间的相互关系，以确定治疗 ARHL 的新靶点。分子途径（AMPK、mTOR、胰岛素/IGF-1 和 sirtuins）和细胞途径（衰老、自噬和氧化应激）的失调已被证明与 ARHL 有关。然而，这些途径在 ARHL 的发生和进展中的机制基础仍需阐明。因此，了解长寿途径与 ARHL 的关系将直接影响治疗或预防 ARHL 的治疗策略的发展。本综述探讨了我们对衰老和听力损失的分子和细胞机制的现有理解，以及它们为 ARHL 的早期诊断、预防和治疗提供新方法的潜力。
