Treaster S B, Ridgway I D, Richardson C A, Gaspar M B, Chaudhuri A R, Austad S N
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX, 78245, USA.
Age (Dordr). 2014 Jun;36(3):9597. doi: 10.1007/s11357-013-9597-9. Epub 2013 Nov 20.
Bivalve mollusks have several unique traits, including some species with exceptionally long lives, others with very short lives, and the ability to determine the age of any individual from growth rings in the shell. Exceptionally long-lived species are seldom studied yet have the potential to be particularly informative with respect to senescence-resistance mechanisms. To this end, we employed a range of marine bivalve mollusk species, with lifespans ranging from under a decade to over 500 years, in a comparative study to investigate the hypothesis that long life requires superior proteome stability. This experimental system provides a unique opportunity to study closely related organisms with vastly disparate longevities, including the longest lived animal, Arctica islandica.Specifically, we investigated relative ability to protect protein structure and function, both basally and under various stressors in our range of species. We found a consistent relationship between species longevity, resistance to protein unfolding, and maintenance of endogenous enzyme (creatine kinase) activity. Remarkably, our longest-lived species, Arctica islandica (maximum longevity >500 years), had no increase in global proteome unfolding in response to several stressors. Additionally, the global proteome of shorter-lived species exhibited less resistance to temperature-induced protein aggregation than longer-lived species. A reporter assay, in which the same protein's aggregation properties was assessed in lysates from each study species, suggests that some endogenous feature in the cells of long-lived species, perhaps small molecular chaperones, was at least partially responsible for their enhanced proteome stability. This study reinforces the relationship between proteostasis and longevity through assessment of unfolding, function, and aggregation in species ranging in longevity from less than a decade to more than five centuries.
双壳贝类软体动物有几个独特的特征，包括一些寿命极长的物种、一些寿命极短的物种，以及通过贝壳上的生长轮来确定任何个体年龄的能力。寿命极长的物种很少被研究，但在抗衰老机制方面可能具有特别的参考价值。为此，我们在一项比较研究中采用了一系列海洋双壳贝类软体动物物种，其寿命从不到十年到超过500年不等，以研究长寿需要卓越蛋白质组稳定性这一假设。这个实验系统提供了一个独特的机会来研究亲缘关系密切但寿命差异极大的生物体，包括最长寿的动物冰岛北极蛤。具体来说，我们研究了在基础状态以及各种应激源作用下，不同物种保护蛋白质结构和功能的相对能力。我们发现物种寿命、对蛋白质解折叠的抗性以及内源性酶（肌酸激酶）活性的维持之间存在一致的关系。值得注意的是，我们最长寿的物种冰岛北极蛤（最长寿命>500年）在面对多种应激源时，其整体蛋白质组解折叠情况并未增加。此外，寿命较短的物种的整体蛋白质组比寿命较长的物种对温度诱导的蛋白质聚集表现出更低的抗性。一项报告基因检测在来自每个研究物种的裂解物中评估了同一蛋白质的聚集特性，结果表明长寿物种细胞中的某些内源性特征，可能是小分子伴侣，至少部分地导致了它们增强的蛋白质组稳定性。这项研究通过评估寿命从不到十年到超过五个世纪的物种的解折叠、功能和聚集情况，强化了蛋白质稳态与寿命之间的关系。
