Epel Elissa S, Lin Jue, Wilhelm Frank H, Wolkowitz Owen M, Cawthon Richard, Adler Nancy E, Dolbier Christyn, Mendes Wendy B, Blackburn Elizabeth H
UCSF Department of Psychiatry, San Francisco, CA, USA.
Psychoneuroendocrinology. 2006 Apr;31(3):277-87. doi: 10.1016/j.psyneuen.2005.08.011. Epub 2005 Nov 17.
We previously reported that psychological stress is linked to and possibly accelerates cellular aging, as reflected by lower PBMC telomerase and shortened telomeres. Psychological stress is a major risk factor for cardiovascular disease (CVD), with multiple behavioral and physiological mediators. Telomere shortness has been associated with CVD, but the relationship between low telomerase activity, a potential precursor to telomere shortening, and CVD risk factors has not been examined in humans. Here we examine whether telomere length and telomerase in leukocytes are associated with physiological signs of stress arousal and CVD risk factors in 62 healthy women. Low telomerase activity in leukocytes was associated with exaggerated autonomic reactivity to acute mental stress and elevated nocturnal epinephrine. Further, low telomerase activity was associated with the major risk factors for CVD -smoking, poor lipid profile, high systolic blood pressure, high fasting glucose, greater abdominal adiposity-as well as to a composite Metabolic Syndrome variable. Telomere length was related only to elevated stress hormones (catecholamines and cortisol). Thus, we propose that low leukocyte telomerase constitutes an early marker of CVD risk, possibly preceding shortened telomeres, that results in part from chronic stress arousal. Possible cellular mechanisms by which low telomerase may link stress and traditional risk factors to CVD are discussed. These findings may implicate telomerase as a novel and important mediator of the effects of psychological stress on physical health and disease.
我们之前报道过,心理压力与细胞衰老相关联,甚至可能加速细胞衰老,这表现为外周血单核细胞端粒酶水平降低和端粒缩短。心理压力是心血管疾病(CVD)的主要危险因素,存在多种行为和生理调节因素。端粒缩短与心血管疾病有关,但在人类中,尚未研究过低端粒酶活性(端粒缩短的潜在先兆)与心血管疾病危险因素之间的关系。在此,我们研究了62名健康女性白细胞中的端粒长度和端粒酶是否与应激唤醒的生理迹象及心血管疾病危险因素相关。白细胞中端粒酶活性低与对急性精神压力的自主反应过度及夜间肾上腺素水平升高有关。此外,低端粒酶活性与心血管疾病的主要危险因素——吸烟、血脂异常、收缩压高、空腹血糖高、腹部肥胖——以及代谢综合征综合变量有关。端粒长度仅与应激激素(儿茶酚胺和皮质醇)升高有关。因此,我们提出,白细胞端粒酶水平低是心血管疾病风险的早期标志物,可能先于端粒缩短出现,这部分是由慢性应激唤醒导致的。我们还讨论了低端粒酶可能将压力和传统危险因素与心血管疾病联系起来的潜在细胞机制。这些发现可能意味着端粒酶是心理压力对身体健康和疾病影响的一种新的重要调节因子。