Special issue on "Molecular genetics of aging and longevity": a critical time in the field of geroscience.
Special issue on "Molecular genetics of aging and longevity": a critical time in the field of geroscience.
复制标题
“衰老与长寿的分子遗传学”特刊：老年科学领域的关键时刻。
DOI：
10.1007/s00439-020-02125-7
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发表时间：
2020
期刊：
影响因子：
5.3
通讯作者：
Veitia,ReinerA
中科院分区：
文献类型：
--
作者：
Benayoun,BéréniceA;Veitia,ReinerA
尽管长期以来，衰老被认为是一种简单且不可避免的衰退，但过去三十年的积累工作表明，这一过程不仅受到高度监管，而且还依赖于外部环境输入（Kennedy 等人，2014 年；Lopez-Otin 等人，2013 年）。事实上，衰老背后的遗传基础的存在在 20 世纪 90 年代初变得明显，因为发现了特定的基因突变，可以使线虫的寿命延长一倍（Kenyon 等人，1993）。自这一开创性发现以来，衰老过程的许多核心“标志”已被描述，包括基因组不稳定、炎症、线粒体功能障碍、蛋白质稳态丧失（即“蛋白质稳态”）和（表观）基因组改变（Kennedy 等人，2014 年；Lopez-Otin 等人，2013 年）。衰老是许多慢性疾病（例如阿尔茨海默病、癌症、心血管功能障碍、糖尿病等）的最大单一危险因素，由于人口老龄化，这些疾病带来的医疗、经济和社会负担日益沉重。毫不奇怪，临床虚弱涉及解剖、生理和分子功能的累积衰退，并且在生物组织的多个层面上都很明显：基因组、表观基因组、组织、器官和生物体。事实上，“老年科学假说”认为衰老是导致许多慢性疾病发展的根本原因（Kennedy 等，2014），因此需要对人类健康采取综合研究方法。对种系和体细胞遗传以及表观遗传改变与环境相互作用的起源和影响进行详细的全基因组和群体研究将为充分了解衰老过程提供可能性。从精准医学的角度来看，将有可能识别出单一或多种发病风险较高的个体，以设计新的预防措施，例如特定的抗衰老治疗。在本期特刊中，我们收集了衰老生物学各个方面专家的文章，旨在阐述衰老特征（即蛋白质稳态、干细胞衰退、基因组不稳定性和染色质改变）表征方面的新进展，并强调衰老领域的新兴主题生物学（即性别差异的重要性、基因组失调的新方面（例如 miRNA 或剪接）以及线粒体基因组学）。第一组概念性文章涵盖的主题总结并扩展了我们对现有衰老特征的了解（Grassmann 等人，2019 年；Innan 等人，2019 年；McNeely 等人，2019 年；Wong 等人，2019 年；Yu 等人，2020 年）。在 Wong 及其同事的综述中，探讨了自噬对衰老和长寿的影响，自噬是细胞大分子回收的关键机制，也是蛋白质稳态的关键（Wong et al. 2019）。 McNeely 及其同事的综述探讨了长寿干细胞终生 DNA 损伤积累的影响（McNeely 等人，2019），而 Yu 等人的综述（2020）则强调染色质完整性的丧失是衰老过程中基因毒性应激的重要来源。 Grassman 及其合作者的最初研究探讨了黄斑变性患者的进行性 Y 染色体非整倍性（Grassmann 等人，2019）。 Innan 及其同事提出了一种人口模型，通过突变和表突变积累来解释与年龄相关的衰弱和发病（Innan 等人，2019）。
Although aging was long considered as a simple and unavoidable decay, accumulating work over the last three decades have revealed that the process is not only highly regulated, but also dependent on external environmental inputs (Kennedy et al. 2014; Lopez-Otin et al. 2013). Indeed, the existence of a genetic basis underlying aging became evident in the early 1990s with the discovery of specific genetic mutations that could double the lifespan of the nematode C. elegans (Kenyon et al. 1993). Since this seminal discovery, a number of core “hallmarks” of the aging process have been described, including genomic instability, inflammation, mitochondrial dysfunction, loss of protein homeostasis (ie,“proteostasis”) and (epi-) genomic alterations (Kennedy et al. 2014; Lopez-Otin et al. 2013). Aging is the single greatest risk factor for many chronic diseases (eg, Alzheimer’s, cancer, cardiovascular dysfunction, diabetes, etc.), which have a growing medical, financial, and societal burden due to the growing aging population. Not surprisingly, clinical frailty involves a cumulative decline in anatomical, physiological and molecular functions and is apparent at multiple levels of biological organization: genome, epigenome, tissues, organs, and the organism. Indeed, the “geroscience hypothesis” posits that aging is the underlying cause leading to the development of many chronic diseases (Kennedy et al. 2014), and thus requires an integrated research approach to human health. Detailed genome wide and populational investigations on the origins and effects of germline and somatic genetic and epigenetic alterations in interaction with the environment will open up the possibility to fully understand the process (es) of aging. From the perspective of precision medicine, it will be possible to identify individuals at higher risk of developing single or multiple morbidities for devising new preventive measures, such as specific senolytic treatments.In this Special Issue, we assembled a collection of articles from expert in various aspects of aging biology, aimed to both lay out novel advances in the characterization of aging hallmarks (ie, protein homeostasis, stem cell decline, genomic instability, and chromatin alterations), as well as highlight emerging topics of interest in the field of aging biology (ie, importance of sex differences, novel aspects of genomic dysregulation such as miRNA or splicing, and mitochondrial genomics). The first conceptual set of articles spans topics that summarize and expand our knowledge of existing hallmarks of aging (Grassmann et al. 2019; Innan et al. 2019; McNeely et al. 2019; Wong et al. 2019; Yu et al. 2020). In the review by Wong and colleagues, the impact of autophagy on aging and longevity, a key mechanism in recycling cellular macromolecules which is key for proteostasis, is explored (Wong et al. 2019). The review by McNeely and colleagues explores the impact of lifelong DNA-damage accumulation of long-lived stem cells (McNeely et al. 2019), whereas the review by Yu et al.(2020) highlights loss of chromatin integrity as an important source of genotoxic stress with aging. The original study by Grassman and collaborators explores progressive Y-chromosome aneuploidy in patients with macular degeneration (Grassmann et al. 2019). Innan and colleagues propose a demographic model to explain age-related frailty and morbidity through mutation and epimutation accumulation (Innan et al. 2019).