Terry Dellara F, Wyszynski Diego F, Nolan Vikki G, Atzmon Gil, Schoenhofen Emily A, Pennington JaeMi Y, Andersen Stacy L, Wilcox Marsha A, Farrer Lindsay A, Barzilai Nir, Baldwin Clinton T, Asea Alexzander
Geriatrics Section, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.
Mech Ageing Dev. 2006 Nov;127(11):862-8. doi: 10.1016/j.mad.2006.08.007. Epub 2006 Oct 6.
Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes.
热休克蛋白是高度保守的蛋白质，在细胞内产生时可保护受到应激的细胞。相比之下，细胞外热休克蛋白70（Hsp70）已被证明具有保护和有害两种作用。在本研究中，我们评估了热休克蛋白70在人类长寿中的潜在作用。由于热休克蛋白对疾病进程、细胞保护和炎症的重要性，我们提出以下假设：（1）百岁老人及其后代的Hsp70水平与对照组不同；（2）与Hsp70相关基因中的等位基因可解释这些差异。在这项横断面研究中，我们评估了参与新英格兰百岁老人研究（NECS）或长寿基因项目（LGP）的参与者的血清Hsp70水平：87名百岁老人（来自LGP）、93名百岁老人的后代（来自NECS）和126名对照组（43名来自NECS，83名来自LGP）。我们还检测了347名百岁老人（266名来自NECS，81名来自LGP）、260名NECS百岁老人的后代以及238名对照组（NECS：53名配偶对照组和106名七十岁后代对照组；LGP：79名配偶对照组）中HSP70 - A1A和HSP70 - A1B基因多态性的基因型和等位基因频率。NECS百岁老人的后代、LGP百岁老人、LGP配偶对照组和NECS对照组的校正后平均血清Hsp70水平（ng/mL）分别为1.05、1.13、3.07、6.93，这表明血清Hsp70水平低与长寿相关；然而，在两个hsp70基因内的两个单核苷酸多态性（SNP）中未发现基因关联。
