Rollins Jarod A, Howard Amber C, Dobbins Sarah K, Washburn Elsie H, Rogers Aric N
Davis Center for Regenerative Biology and Medicine, Mount Desert Island Biological Laboratory, Bar Harbor, Maine.
College of Arts and Sciences, University of Maine at Augusta.
J Gerontol A Biol Sci Med Sci. 2017 Apr 1;72(4):473-480. doi: 10.1093/gerona/glw248.
Genetic changes resulting in increased life span are often positively associated with enhanced stress resistance and somatic maintenance. A recent study found that certain long-lived Caenorhabditis elegans mutants spent a decreased proportion of total life in a healthy state compared with controls, raising concerns about how the relationship between health and longevity is assessed. We evaluated seven markers of health and two health-span models for their suitability in assessing age-associated health in invertebrates using C elegans strains not expected to outperform wild-type animals. Additionally, we used an empirical method to determine the transition point into failing health based on the greatest rate of change with age for each marker. As expected, animals with mutations causing sickness or accelerated aging had reduced health span when compared chronologically to wild-type animals. Physiological health span, the proportion of total life spent healthy, was reduced for locomotion markers in chronically ill mutants, but, surprisingly, was extended for thermotolerance. In contrast, all short-lived mutants had reduced "quality-of-life" in another model recently employed for assessing invertebrate health. Results suggest that the interpretation of physiological health span is not straightforward, possibly because it factors out time and thus does not account for the added cost of extrinsic forces on longer-lived strains.
导致寿命延长的基因变化通常与增强的抗应激能力和体细胞维持能力呈正相关。最近一项研究发现,与对照组相比,某些长寿的秀丽隐杆线虫突变体在健康状态下度过的总寿命比例有所下降,这引发了人们对如何评估健康与长寿之间关系的担忧。我们评估了七个健康指标和两个健康跨度模型,以确定它们在使用预期不会优于野生型动物的秀丽隐杆线虫品系评估无脊椎动物年龄相关健康状况方面的适用性。此外,我们使用一种实证方法,根据每个指标随年龄变化的最大速率来确定进入健康衰退的转折点。正如预期的那样,与野生型动物按时间顺序比较时,患有疾病或加速衰老突变的动物健康跨度缩短。在慢性病突变体中,生理健康跨度(即健康状态下度过的总寿命比例)在运动指标方面有所降低,但令人惊讶的是,在耐热性方面有所延长。相比之下,在最近用于评估无脊椎动物健康的另一个模型中,所有短寿命突变体的“生活质量”都有所下降。结果表明,生理健康跨度的解释并非直截了当,可能是因为它排除了时间因素,因此没有考虑到外在因素对长寿品系增加的成本。