Significance: 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.
Critical issues: 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.
Future directions: 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.
Keywords: Alzheimer's; aging; biomarkers; diet restriction; neurodegenerative disease; systems biology.