Emerging Omics Approaches in Aging Research.

SIGNIFICANCE: Aging is a complex trait that is influenced by a combination of genetic and environmental factors. Although many cellular and physiological changes have been described to occur with aging, the precise molecular causes of aging remain unknown. Given the biological complexity and heterogeneity of the aging process, understanding the mechanisms that underlie aging requires integration of data about age-dependent changes that occur at the molecular, cellular, tissue, and organismal levels. Recent Advances: The development of high-throughput technologies such as next-generation sequencing, proteomics, metabolomics, and automated imaging techniques provides researchers with new opportunities to understand the mechanisms of aging. Using these methods, millions of biological molecules can be simultaneously monitored during the aging process with high accuracy and specificity. CRITICAL ISSUES: Although the ability to produce big data has drastically increased over the years, integration and interpreting of high-throughput data to infer regulatory relationships between biological factors and identify causes of aging remain the major challenges. In this review, we describe recent advances and survey emerging omics approaches in aging research. We then discuss their limitations and emphasize the need for the further development of methods for the integration of different types of data. FUTURE DIRECTIONS: Combining omics approaches and novel methods for single-cell analysis with systems biology tools would allow building interaction networks and investigate how these networks are perturbed with aging and disease states. Together, these studies are expected to provide a better understanding of the aging process and could provide insights into the pathophysiology of many age-associated human diseases. Antioxid. Redox Signal. 29, 985-1002.

CAN1 Arginine Permease Deficiency Extends Yeast Replicative Lifespan via Translational Activation of Stress Response Genes.

Transcriptional regulation plays an important role in the control of gene expression during aging. However, translation efficiency likely plays an equally important role in determining protein abundance, but it has been relatively understudied in this context. Here, we used RNA sequencing (RNA-seq) and ribosome profiling to investigate the role of translational regulation in lifespan extension by CAN1 gene deletion in yeast. Through comparison of the transcriptional and translational changes in cells lacking CAN1 with other long-lived mutants, we were able to identify critical regulatory factors, including transcription factors and mRNA-binding proteins, that coordinate transcriptional and translational responses. Together, our data support a model in which deletion of CAN1 extends replicative lifespan through increased translation of proteins that facilitate cellular response to stress. This study extends our understanding of the importance of translational control in regulating stress resistance and longevity.