文章基本信息

标题：Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants
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作者：Ankita Bansal ; Lihua J. Zhu ; Kelvin Yen 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：3
页码：E277-E286
DOI：10.1073/pnas.1412192112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceGenetic and environmental manipulations have been identified that result in lifespan extension. The underlying assumption that lifespan extension would also result in an increase in healthspan is seemingly valid but infrequently examined. Here, we examined multiple pathways that modulate lifespan to investigate the relationship between lifespan extension and health. We analyzed wild-type and four long-lived mutants in an unbiased cross-sectional study with multiple assays until animals reached 80% maximum lifespan. We show lifespan and healthspan can be separated and all of the long-lived mutants extend the period of frailty as a consequence. If applied to humans, this would likely lead to unsustainable healthcare costs and demonstrates the importance of examining healthspan as opposed to lifespan for future research. Aging research has been very successful at identifying signaling pathways and evolutionarily conserved genes that extend lifespan with the assumption that an increase in lifespan will also increase healthspan. However, it is largely unknown whether we are extending the healthy time of life or simply prolonging a period of frailty with increased incidence of age-associated diseases. Here we use Caenorhabditis elegans, one of the premiere systems for lifespan studies, to determine whether lifespan and healthspan are intrinsically correlated. We conducted multiple cellular and organismal assays on wild type as well as four long-lived mutants (insulin/insulin-like growth factor-1, dietary restriction, protein translation, mitochondrial signaling) in a longitudinal manner to determine the health of the animals as they age. We find that some long-lived mutants performed better than wild type when measured chronologically (number of days). However, all long-lived mutants increased the proportion of time spent in a frail state. Together, these data suggest that lifespan can no longer be the sole parameter of interest and reveal the importance of evaluating multiple healthspan parameters for future studies on antiaging interventions.
关键词：healthspan ; lifespan ; gerospan ; functional capacity ; healthy aging