Laboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS UMR5239, INSERM 1210, University Claude Bernard Lyon 1, 69364 Lyon, France.
INMG, MeLiS, CNRS UMR 5284, INSERM U1314, University Claude Bernard Lyon 1, 69008 Lyon, France.
Cells. 2024 Feb 5;13(3):288. doi: 10.3390/cells13030288.
The aging process is inherently complex, involving multiple mechanisms that interact at different biological scales. The nematode is a simple model organism that has played a pivotal role in aging research following the discovery of mutations extending lifespan. Longevity pathways identified in were subsequently found to be conserved and regulate lifespan in multiple species. These pathways intersect with fundamental hallmarks of aging that include nutrient sensing, epigenetic alterations, proteostasis loss, and mitochondrial dysfunction. Here we summarize recent data obtained in highlighting the importance of studying aging at both the tissue and temporal scale. We then focus on the neuromuscular system to illustrate the kinetics of changes that take place with age. We describe recently developed tools that enabled the dissection of the contribution of the insulin/IGF-1 receptor ortholog DAF-2 to the regulation of worm mobility in specific tissues and at different ages. We also discuss guidelines and potential pitfalls in the use of these new tools. We further highlight the opportunities that they present, especially when combined with recent transcriptomic data, to address and resolve the inherent complexity of aging. Understanding how different aging processes interact within and between tissues at different life stages could ultimately suggest potential intervention points for age-related diseases.
衰老是一个复杂的过程,涉及到多个在不同生物学尺度上相互作用的机制。线虫是一种简单的模式生物,自从发现可以延长寿命的突变以来,它在衰老研究中发挥了关键作用。在 中发现的长寿途径随后被发现是保守的,并调节多种物种的寿命。这些途径与衰老的基本特征相交,包括营养感应、表观遗传改变、蛋白质稳态丧失和线粒体功能障碍。在这里,我们总结了在 中获得的最新数据,强调了在组织和时间尺度上研究衰老的重要性。然后,我们将重点放在神经肌肉系统上,以说明随着年龄的增长而发生的变化的动力学。我们描述了最近开发的工具,这些工具使我们能够在特定组织和不同年龄时,分析胰岛素/IGF-1 受体同源物 DAF-2 对线虫运动性的调节作用。我们还讨论了使用这些新工具的指导方针和潜在陷阱。我们进一步强调了它们带来的机会,特别是当与最近的转录组数据结合使用时,可以解决衰老过程中固有的复杂性。了解不同的衰老过程如何在不同生命阶段的不同组织内和组织之间相互作用,最终可能会为与年龄相关的疾病提供潜在的干预点。
Mol Cells. 2022-11-30
EMBO Rep. 2018-6-26
WormBook. 2013-12-26
Int J Mol Sci. 2024-4-20
Trends Genet. 2023-12
Sci Adv. 2023-6-23
Mech Ageing Dev. 2023-7