Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Ontario, Canada.
Department of Internal Medicine, The University of New Mexico, Albuquerque, New Mexico.
J Appl Physiol (1985). 2021 Jan 1;130(1):1-9. doi: 10.1152/japplphysiol.00542.2020. Epub 2020 Oct 29.
Autophagy is a crucial cell survival mechanism that involves the degradation and recycling of old or damaged organelles and proteins to maintain cellular homeostasis. Impairments in autophagy are central to the pathogenesis of many conditions including metabolic and neurodegenerative disorders, cardiovascular and pulmonary diseases, diabetes, and aging. Although various pharmacological agents may be able to stimulate autophagic function, to our knowledge, few interventions exist that have been deemed safe and effective in humans. An emerging body of evidence suggests that targeting the autophagic pathway via passive heating (heat therapy) may stimulate autophagic function. Therefore, the primary focus of the present review is to analyze the mechanisms in which passive heating induces autophagy as defined by in vitro and in vivo (animal and human) models. Our secondary focus is to examine the implications of utilizing passive heating to restore dysfunctional autophagy in chronic disease and aging. Finally, we discuss potential therapeutic strategies to implement passive heating to stimulate autophagic function in humans.
自噬是一种重要的细胞存活机制,涉及到旧的或受损细胞器和蛋白质的降解和再循环,以维持细胞内的平衡。自噬的损伤是许多疾病发病机制的核心,包括代谢和神经退行性疾病、心血管和肺部疾病、糖尿病和衰老。虽然各种药理学制剂可能能够刺激自噬功能,但据我们所知,在人类中,几乎没有被认为是安全有效的干预措施。越来越多的证据表明,通过被动加热(热疗)靶向自噬途径可能会刺激自噬功能。因此,本综述的主要重点是分析体外和体内(动物和人类)模型中被动加热诱导自噬的机制。我们的次要重点是研究利用被动加热来恢复慢性疾病和衰老中功能失调的自噬的意义。最后,我们讨论了在人类中实施被动加热以刺激自噬功能的潜在治疗策略。