With an ageing population comes an inevitable increase in the prevalence of age-associated neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a relentlessly progressive and universally fatal disease characterized by the degeneration of upper and lower motor neurons within the brain and spinal cord. Indeed, the physiological process of ageing causes a variety of molecular and cellular phenotypes. With dysfunction at the neuromuscular junction implicated as a key pathological mechanism in ALS, and each lower motor unit cell type vulnerable to its own set of age-related phenotypes, the effects of ageing might in fact prove a prerequisite to ALS, rendering the cells susceptible to disease-specific mechanisms. Moreover, we discuss evidence for overlap between age and ALS-associated hallmarks, potentially implicating cell type-specific ageing as a key contributor to this multifactorial and complex disease. With a dearth of disease-modifying therapy currently available for ALS patients and a substantial failure in bench to bedside translation of other potential therapies, the unification of research in ageing and ALS requires high fidelity models to better recapitulate age-related human disease and will ultimately yield more reliable candidate therapeutics for patients, with the aim of enhancing healthspan and life expectancy.

中文翻译：

---

解码衰老与肌萎缩侧索硬化症之间的关系：细胞视角。

随着人口老龄化，与年龄相关的神经退行性疾病的患病率不可避免地增加，例如肌萎缩侧索硬化症（ALS），这是一种持续进展且普遍致命的疾病，其特征是大脑和脊髓内上下运动神经元的退化。事实上，衰老的生理过程会导致多种分子和细胞表型。由于神经肌肉接头功能障碍是 ALS 的一个关键病理机制，并且每种下运动单位细胞类型都容易受到其自身一组与年龄相关的表型的影响，因此衰老的影响实际上可能被证明是 ALS 的先决条件，从而使细胞易受影响疾病特异性机制。此外，我们讨论了年龄和 ALS 相关特征之间重叠的证据，这可能表明细胞类型特异性衰老是这种多因素复杂疾病的关键因素。由于目前可用于 ALS 患者的疾病缓解疗法十分匮乏，而且其他潜在疗法从实验室到临床的转化也严重失败，衰老和 ALS 研究的统一需要高保真度模型来更好地概括与年龄相关的人类疾病，并最终将为患者提供更可靠的候选疗法，旨在延长健康寿命和预期寿命。