Aging is a pathophysiological process that causes a gradual and permanent reduction in all biological system functions. The phenomenon is caused by the accumulation of endogenous and exogenous damage as a result of several stressors, resulting in significantly increased risks of various age-related diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. In addition, aging appears to be connected with mis-regulation of programmed cell death (PCD), which is required for regular cell turnover in many tissues sustained by cell division. According to the recent nomenclature, PCDs are physiological forms of regulated cell death (RCD) useful for normal tissue development and turnover. To some extent, some cell types are connected with a decrease in RCD throughout aging, whereas others are related with an increase in RCD. Perhaps the widespread decline in RCD markers with age is due to a slowdown of the normal rate of homeostatic cell turnover in various adult tissues. As a result, proper RCD regulation requires a careful balance of many pro-RCD and anti-RCD components, which may render cell death signaling pathways more sensitive to maladaptive signals during aging. Current research, on the other hand, tries to further dive into the pathophysiology of aging in order to develop therapies that improve health and longevity. In this scenario, RCD handling might be a helpful strategy for human health since it could reduce the occurrence and development of age-related disorders, promoting healthy aging and lifespan. In this review we propose a general overview of the most recent RCD mechanisms and their connection with the pathophysiology of aging in order to promote targeted therapeutic strategies.

中文翻译：

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受调节的细胞死亡参与衰老和与年龄相关的病理学

衰老是一种病理生理过程，会导致所有生物系统功能逐渐且永久的降低。这种现象是由于多种应激源导致内源性和外源性损伤累积，导致神经退行性疾病、心血管疾病、代谢性疾病、肌肉骨骼疾病、免疫系统疾病等各种与年龄相关的疾病的风险显着增加。此外，衰老似乎与程序性细胞死亡（PCD）的错误调节有关，而程序性细胞死亡（PCD）是许多组织中细胞分裂维持的正常细胞周转所必需的。根据最近的命名法，PCD 是调节性细胞死亡 (RCD) 的生理形式，有助于正常组织的发育和更新。在某种程度上，某些细胞类型与整个衰老过程中 RCD 的减少有关，而其他细胞类型则与 RCD 的增加有关。也许 RCD 标记物随着年龄的增长而普遍下降是由于各种成人组织中稳态细胞更新的正常速率减慢。因此，正确的 RCD 调节需要仔细平衡许多促 RCD 和抗 RCD 成分，这可能会使细胞死亡信号通路对衰老过程中的适应不良信号更加敏感。另一方面，当前的研究试图进一步深入研究衰老的病理生理学，以开发改善健康和长寿的疗法。在这种情况下，RCD处理可能是对人类健康有益的策略，因为它可以减少与年龄相关的疾病的发生和发展，促进健康老龄化和寿命。在这篇综述中，我们对最新的 RCD 机制及其与衰老病理生理学的联系进行了总体概述，以促进有针对性的治疗策略。