PDF(Pubmed)
Abstract：
Biological aging, and the diseases of aging, occur in a complex in vivo environment, driven by multiple interacting processes. A convergence of recently developed technologies has enabled in vivo pooled screening: direct administration of a library of different perturbations to a living animal, with a subsequent readout that distinguishes the identity of each perturbation and its effect on individual cells within the animal. Such screens hold promise for efficiently applying functional genomics to aging processes in the full richness of the in vivo setting. In this review, we describe the technologies behind in vivo pooled screening, including a range of options for delivery, perturbation and readout methods, and outline their potential application to aging and age-related disease. We then suggest how in vivo pooled screening, together with emerging innovations in each of its technological underpinnings, could be extended to shed light on key open questions in aging biology, including the mechanisms and limits of epigenetic reprogramming and identifying cellular mediators of systemic signals in aging.
摘要：
生物老化,和衰老的疾病，发生在复杂的体内环境中，由多个交互过程驱动。最近开发的技术的融合使体内集中筛选成为可能：将不同扰动的文库直接施用给活体动物，随后的读数可区分每种扰动的身份及其对动物体内单个细胞的影响。这样的筛选有望在体内设置的全部丰富度中将功能基因组学有效地应用于衰老过程。在这次审查中,我们描述了体内集中筛查背后的技术，包括一系列交付选项，摄动和读出方法，并概述了它们在衰老和年龄相关疾病中的潜在应用。然后，我们建议如何在体内集中筛选，连同其每个技术基础的新兴创新，可以扩展到揭示衰老生物学中的关键悬而未决的问题，包括表观遗传重编程的机制和限制，以及识别衰老中系统信号的细胞介质。
