1 Buck Institute for Research on Aging , Novato, California.
2 Department of Pathology, University of Washington , Seattle, Washington.
Antioxid Redox Signal. 2018 Oct 1;29(10):973-984. doi: 10.1089/ars.2017.7367. Epub 2017 Nov 20.
Reductionist studies have contributed greatly to our understanding of the basic biology of aging in recent years but we still do not understand fundamental mechanisms for many identified drugs and pathways. Use of systems approaches will help us move forward in our understanding of aging. Recent Advances: Recent work described here has illustrated the power of systems biology to inform our understanding of aging through the study of (i) diet restriction, (ii) neurodegenerative disease, and (iii) biomarkers of aging.
Although we do not understand all of the individual genes and pathways that affect aging, as we continue to uncover more of them, we have now also begun to synthesize existing data using systems-level approaches, often to great effect. The three examples noted here all benefit from computational approaches that were unknown a few years ago, and from biological insights gleaned from multiple model systems, from aging laboratories as well as many other areas of biology.
Many new technologies, such as single-cell sequencing, advances in epigenetics beyond the methylome (specifically, assay for transposase-accessible chromatin with high throughput sequencing ), and multiomic network studies, will increase the reach of systems biologists. This suggests that approaches similar to those described here will continue to lead to striking findings, and to interventions that may allow us to delay some of the many age-associated diseases in humans; perhaps sooner that we expect. Antioxid. Redox Signal. 29, 973-984.
近年来,还原论研究极大地促进了我们对衰老基础生物学的理解,但我们仍然不了解许多已确定的药物和途径的基本机制。系统方法的使用将帮助我们在理解衰老方面取得进展。
这里描述的最近的工作说明了系统生物学的力量,通过研究(i)饮食限制,(ii)神经退行性疾病,和(iii)衰老标志物,来告知我们对衰老的理解。
虽然我们并不了解所有影响衰老的单个基因和途径,但随着我们继续发现更多的基因和途径,我们现在也已经开始使用系统水平的方法来综合现有的数据,通常效果显著。这里提到的三个例子都受益于几年前未知的计算方法,以及从多个模型系统、衰老实验室以及许多其他生物学领域中获得的生物学见解。
许多新技术,如单细胞测序、超越甲基组的表观遗传学进展(特别是高通量测序的转座酶可及染色质检测),以及多组学网络研究,将扩大系统生物学家的研究范围。这表明,类似于这里描述的方法将继续带来惊人的发现,并可能为我们提供干预措施,以延缓人类的许多与年龄相关的疾病;也许比我们预期的要早。抗氧化还原信号。29,973-984。