Determining Age-Dependent Metabolic Changes in Tumors and Their Microenvironment

标题：确定肿瘤及其微环境中的β-依赖性代谢变化 项目科学领域：6个MCB，8个HIB 项目概要/摘要： 衰老是癌症的主要危险因素之一，代谢失调是癌症的统一标志。 衰老和癌症然而，我们并不完全了解与年龄相关的代谢变化如何有助于 癌症的发生和发展。尽管许多动物模型被创造出来， 导致细胞转化和癌症进展的致癌事件，大多数发生在年轻人中， 这些动物可能具有代谢不同的肿瘤微环境和强大的免疫系统。本 迄今为止，很少有研究系统地研究了细胞和生物体的年龄依赖性变化是如何发生的。 代谢影响肿瘤生长和转移。我们假设年龄相关的代谢失调 将显著改变肿瘤细胞内以及肿瘤内细胞的细胞代谢 微环境，这可能会影响癌症的进展和对治疗的反应。我们提出了一个 多管齐下的单细胞方法来表征和解决随时间推移的代谢变化， 肿瘤及其微环境最后，我们将评估环境因素的影响，如饮食 营养素和微生物组衍生的代谢物，对癌症的发生和发展。总体而言，我们认为 这些发现将是变革性的，并将回答衰老如何重新连接细胞代谢以及如何改变细胞代谢的关键问题。 它影响肿瘤生长和转移。我们希望阐明细胞可塑性的重要问题， 代谢异质性，并确定代谢负债，可以通过限制特定的营养素或 新的组合疗法中的代谢物。

Title: Determining Age-Dependent Metabolic Changes in Tumors and Their Microenvironment Project science areas: 6 MCB, 8 HIB Project Summary/Abstract: Aging is one of the primary risk factors for cancer and deregulated metabolism is a unifying hallmark for both aging and cancer. Yet, we do not fully understand how ageassociated metabolic changes contribute to cancer initiation and progression. Although many animal models are created to fatefully recapitulate the oncogenic events that lead to cellular transformation and cancer progression, most are carried out in young animals that likely have metabolically different tumor microenvironments and robust immune systems. To this date, few studies have systematically examined how age-dependent alterations of cellular and organismal metabolism impact tumor growth and metastasis. We hypothesize that age-associated metabolic dysregulation will significantly alter cellular metabolism both within tumor cells, as well as in cells within the tumor microenvironment, which may influence cancer progression and response to therapies. We propose a multipronged, single cell approach to characterize and resolve metabolic changes over time, both within the tumor and its microenvironment. Finally, we will assess the impact of environmental factors, such as dietary nutrients and microbiome derived metabolites, on cancer initiation and progression. Collectively, we think our findings will be transformative and will answer key questions of how aging rewires cellular metabolism and how it affects tumor growth and metastasis. We hope to elucidate important questions about cellular plasticity, metabolic heterogeneity and identify metabolic liabilities that can be accentuated by limiting specific nutrients or metabolites in new combinatorial therapies.