Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience
Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience
复制标题
DOI：
10.1093/gerona/glw106
复制
发表时间：
2016-11-01
影响因子：
5.1
通讯作者：
Austad, Steven N.
中科院分区：
文献类型：
--
作者：
Huffman, Derek M.;Justice, Jamie N.;Austad, Steven N.
延长寿命不再被认为是研究动物延缓衰老的充分证据。还必须证明，广泛的健康指标已经得到扩展。在老年科学网络(一个由基础和临床衰老研究人员组成的联盟)的一次撤退中，老鼠健康的潜在指标被认为是容易标准化的、高度信息量的指标。被考虑的主要健康领域是神经肌肉、认知、心血管、代谢和炎症功能以及身体成分和能量学，并对这些领域进行了大量的测试。衡量健康的一个特别敏感的指标是应对压力和从压力中恢复的能力。因此，该网络还考虑了可以在小鼠模型中实施的与人类相关的压力，以评估脆弱性和复原力。已经存在对强迫不动、癌症化疗、传染病、饮食挑战和手术压力做出反应的小鼠模型，人们认为这些模型可以用来确定假定的延缓衰老干预是否增加和延长了组织的健壮性。该网络讨论了在为与年龄有关的人类慢性疾病建模方面面临的挑战，并得出结论，需要更多地注意开发起病年龄较晚的疾病模型、共病和多发病模型、使老龄化研究中常用的菌株和性别多样化以及考虑更多的物种。
Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species.