An organism's health depends on the integrity of molecular and biochemical networks responsible for ensuring homeostasis within its cells and tissues. However, upon aging, a progressive failure in the maintenance of this homeostatic balance occurs in response to various insults, allowing the accumulation of damage, the physiological decline of individual tissues, and susceptibility to diseases. Despite the complex nature of the aging process, simple genetic and environmental alterations can cause an increase in healthy lifespan or “healthspan” in laboratory model organisms. Genetic manipulations of model organisms including yeast, worms, flies, and mice have revealed signaling elements involved in DNA damage, stem cells maintenance, proteostasis, energy, and oxidative metabolism (Riera et al., 2016). However, one of the most intriguing discoveries made in these models resides in the ability of environmental factors to profoundly alter the aging process by remodeling some of the genetic programs mentioned above (Riera and Dillin, 2016). The first line of evidence that an external cue could powerfully regulate longevity was obtained by performing dietary restriction in rodents, a reduction in food intake without malnutrition. Dietary restriction is the most robust intervention to increase lifespan in model organisms including rodents and primates, and delays the emergence of age-related diseases (Mair and Dillin, 2008). How dietary restriction extends lifespan remains an open question, but decades of research are evidencing molecular pathways embedded in the response to reduce energy availability, resulting in the emergence of an altered metabolic state that promotes health and longevity. Nonetheless, the discovery of dietary restriction opened a new avenue of research in the aging field, and in particular in the understanding of how animals deal with fluctuating energy levels in their natural environment, and how their longevity is affected by such factors. This is particularly relevant for the nematode , which survives in a changing environment and must be able to coordinate energy-demanding processes including basal cellular functions, growth, reproduction, and physical activity with available external resources. In order to sense their environment, possess ciliated sensory neurons located primarily in sensory organs in the head and tail regions. Cilia function as sensory receptors, expressing many G protein-coupled receptors (GPCRs) and transient receptor potential (TRP) channels, and mutants with defective sensory cilia have impaired sensory perception (Bargmann, 2006). Cilia are membrane-bound microtubule-based structures and in are only found at the dendritic endings of sensory neurons. Sensory neurons provide nematodes with a remarkable form of developmental plasticity, allowing them to assess food availability, temperature, and crowding information (worm density) in order to arrest their development if required, thus forming long-lived and stress-resistant dauer larvae (Bargmann, 2006; Golden and Riddle, 1982). When favorable times return, worms assess the same cues to recover and resume normal development. As the entry and exit of the dauer larval stage suggest, worm sensory neurons truly function as neuroendocrine organs, being implicated in many physiological functions in addition to their behavioral role (Bargmann, 2006). Much information on these neurons has been gathered from laser ablation experiments and analysis of mutants presenting defects in sensory cilia. A seminal discovery in the aging field was achieved when the laboratory of Cynthia Kenyon showed in 1999 that mutations that cause various defects in cilia formation, including the absence of cilia, deletion of middle and distal segments, or impair chemosensory signal transduction increase longevity profoundly (Apfeld and Kenyon, 1999). Later, this group also demonstrated that laser ablation of specific pairs of gustatory and olfactory chemosensory neurons was sufficient to extend lifespan (Alcedo and Kenyon, 2004). What is the role of TRP channels in modulating these neuroendocrine processes, and what kind of stimuli are these receptors detecting to control aging? This chapter summarizes relevant discoveries that clarify some of the roles of TRP channels in the aging process.
生物体的健康取决于分子和生化网络的完整性，这些网络负责确保其细胞和组织内的稳态。然而，随着年龄的增长，由于各种损伤，维持这种稳态平衡的过程会逐渐失效，从而导致损伤的积累、单个组织的生理衰退以及对疾病的易感性。尽管衰老过程具有复杂性，但简单的基因和环境改变可以延长实验室模式生物的健康寿命或“健康跨度”。对包括酵母、蠕虫、果蝇和小鼠在内的模式生物进行基因操作，揭示了参与DNA损伤、干细胞维持、蛋白质稳态、能量和氧化代谢的信号元件（里埃拉等人，2016年）。然而，在这些模型中最引人入胜的发现之一是环境因素能够通过重塑上述一些基因程序深刻改变衰老过程（里埃拉和迪林，2016年）。通过对啮齿动物进行饮食限制获得了第一条证据，即外部信号可以有力地调节寿命，饮食限制是在不造成营养不良的情况下减少食物摄入量。饮食限制是在包括啮齿动物和灵长类动物在内的模式生物中延长寿命最有效的干预措施，并能延缓与年龄相关疾病的出现（迈尔和迪林，2008年）。饮食限制如何延长寿命仍然是一个悬而未决的问题，但数十年的研究表明，在应对能量供应减少的反应中存在分子途径，导致出现一种促进健康和长寿的代谢状态改变。尽管如此，饮食限制的发现为衰老领域开辟了一条新的研究途径，特别是在理解动物如何应对其自然环境中波动的能量水平以及这些因素如何影响它们的寿命方面。这对线虫尤为重要，线虫在不断变化的环境中生存，必须能够将包括基础细胞功能、生长、繁殖和体力活动等需要能量的过程与可用的外部资源相协调。为了感知环境，线虫拥有主要位于头部和尾部感觉器官中的纤毛感觉神经元。纤毛作为感觉受体，表达许多G蛋白偶联受体（GPCR）和瞬时受体电位（TRP）通道，感觉纤毛有缺陷的突变体的感觉能力受损（巴格曼，2006年）。纤毛是基于膜结合微管的结构，在线虫中仅存在于感觉神经元的树突末端。感觉神经元为线虫提供了一种显著的发育可塑性形式，使它们能够评估食物供应、温度和拥挤信息（线虫密度），以便在需要时停止发育，从而形成长寿且抗应激的 dauer 幼虫（巴格曼，2006年；戈尔登和里德尔，1982年）。当有利时机到来时，线虫评估相同的线索以恢复并重新开始正常发育。正如 dauer 幼虫阶段的进入和退出所表明的，线虫感觉神经元真正作为神经内分泌器官发挥作用，除了其行为作用外，还参与许多生理功能（巴格曼，2006年）。关于这些神经元的许多信息是通过激光消融实验和对感觉纤毛有缺陷的突变体的分析收集到的。1999年，辛西娅·凯尼恩的实验室取得了衰老领域的一项开创性发现，即导致纤毛形成各种缺陷的突变，包括纤毛缺失、中间和远端节段缺失或化学感觉信号转导受损，会显著延长寿命（阿费尔德和凯尼恩，1999年）。后来，该团队还证明，对特定的味觉和嗅觉化学感觉神经元对进行激光消融足以延长寿命（阿尔塞多和凯尼恩，2004年）。TRP通道在调节这些神经内分泌过程中起什么作用，这些受体检测到什么样的刺激来控制衰老？本章总结了相关发现，阐明了TRP通道在衰老过程中的一些作用。
