Golubev Aleksei G
N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia.
Front Physiol. 2020 Dec 3;11:584248. doi: 10.3389/fphys.2020.584248. eCollection 2020.
The death toll of the current COVID-19 pandemic is strongly biased toward the elderly. COVID-19 case fatality rate (CFR) increases with age exponentially, its doubling time being about 7 years, irrespective of countries and epidemic stages. The same age-dependent mortality pattern known as the Gompertz law is featured by the total mortality and its main constituents attributed to cardiovascular, metabolic, neurological, and oncological diseases. Among patients dying of COVID-19, most have at least one of these conditions, whereas none is found in most of those who pass it successfully. Thus, gerontology is indispensable in dealing with the pandemic, which becomes a benchmark for validating the gerontological concepts and advances. The two basic alternative gerontological concepts imply that either aging results from the accumulation of stochastic damage, or is programmed. Based on these different grounds, several putative anti-aging drugs have been proposed as adjuvant means for COVID-19 prevention and/or treatment. These proposals are reviewed in the context of attributing the molecular targets of these drugs to the signaling pathways between the sensors of resource availability and the molecular mechanisms that allocate resources to storage, growth and reproduction or to self-maintenance and repair. Each of the drugs appears to reproduce only a part of the physiological responses to reduced resource availability caused by either dietary calories restriction or physical activity promotion, which are the most robust means of mitigating the adverse manifestations of aging. In the pathophysiological terms, the conditions of the endothelium, which worsen as age increases and may be significantly improved by the physical activity, is a common limiting factor for the abilities to withstand both physical stresses and challenges imposed by COVID-19. However, the current anti-epidemic measures promote sedentary indoor lifestyles, at odds with the most efficient behavioral interventions known to decrease the vulnerability to both the severe forms of COVID-19 and the prevalent aging-associated diseases. To achieve a proper balance in public health approaches to COVID-19, gerontologists should be involved in crosstalk between virologists, therapists, epidemiologists, and policy makers. The present publication suggests a conceptual background for that.
当前新冠疫情的死亡人数严重偏向老年人。新冠病毒病病死率（CFR）随年龄呈指数增长，其倍增时间约为7年，与国家和疫情阶段无关。同样的年龄依赖性死亡模式，即冈珀茨定律，也体现在总死亡率及其主要构成部分上，这些主要构成部分归因于心血管疾病、代谢疾病、神经疾病和肿瘤疾病。在死于新冠病毒病的患者中，大多数至少患有这些疾病中的一种，而在大多数成功康复的患者中则未发现这些疾病。因此，老年医学在应对这场疫情中不可或缺，这场疫情成为验证老年医学概念和进展的一个基准。两种基本的老年医学替代概念意味着，衰老要么是随机损伤积累的结果，要么是被编程的。基于这些不同的依据，已经提出了几种假定的抗衰老药物作为预防和/或治疗新冠病毒病的辅助手段。这些提议将在以下背景下进行综述：将这些药物的分子靶点归因于资源可用性传感器与将资源分配用于储存、生长和繁殖或自我维持和修复的分子机制之间的信号通路。每种药物似乎只重现了因饮食热量限制或体育活动增加导致资源可用性降低时生理反应的一部分，而饮食热量限制和体育活动增加是减轻衰老不良表现的最有效手段。从病理生理学角度来看，内皮状况会随着年龄增长而恶化，而体育活动可能会使其得到显著改善，内皮状况是承受身体压力和新冠病毒病带来的挑战能力的一个常见限制因素。然而，当前的抗疫措施促进了久坐不动的室内生活方式，这与已知的最有效的行为干预措施背道而驰，这些行为干预措施可降低患重症新冠病毒病和常见的与衰老相关疾病的易感性。为了在应对新冠病毒病的公共卫生方法中实现适当平衡，老年医学专家应参与病毒学家、治疗师、流行病学家和政策制定者之间的对话。本出版物为此提供了一个概念背景。
