Kavathia Nilay, Jain Alka, Walston Jeremy, Beamer Brock A, Fedarko Neal S
Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.
Aging (Albany NY). 2009 Jul 14;1(7):652-63. doi: 10.18632/aging.100069.
The physical manifestations of aging reflect a loss of homeostasis that effects molecular, cellular and organ system functional capacity. As a sentinel homeostatic pathway, changes in apoptosis can have pathophysiological consequences in both aging and disease. To assess baseline global apoptosis balance, sera from 204 clinically normal subjects had levels of sFas (inhibitor of apoptosis), sFasL (stimulator of apoptosis), and total cytochrome c (released from cells during apoptosis) measured. Serum levels of sFas were significantly higher while sFasL and cytochrome c levels were lower in men compared to women. With increasing age there was a decrease in apoptotic markers (cytochrome c) and pro-apoptotic factors (sFasL) and an increase in anti-apoptotic factors (sFas) in circulation. The observed gender differences are consistent with the known differences between genders in mortality and morbidity. In a separate cohort, subjects with either breast (n = 66) or prostate cancer (n = 38) exhibited significantly elevated sFas with reduced sFasL and total cytochrome c regardless of age. These markers correlated with disease severity consistent with tumor subversion of apoptosis. The shift toward less global apoptosis with increasing age in normal subjects is consistent with increased incidence of diseases whose pathophysiology involves apoptosis dysregulation.
衰老的身体表现反映了体内稳态的丧失，这种丧失会影响分子、细胞和器官系统的功能能力。作为一种重要的体内稳态途径，细胞凋亡的变化在衰老和疾病中都可能产生病理生理后果。为了评估基线整体细胞凋亡平衡，对204名临床正常受试者的血清进行了检测，测量了可溶性Fas（细胞凋亡抑制剂）、可溶性Fas配体（细胞凋亡刺激剂）和总细胞色素c（细胞凋亡期间从细胞中释放）的水平。与女性相比，男性血清中可溶性Fas水平显著更高，而可溶性Fas配体和细胞色素c水平更低。随着年龄的增长，循环中细胞凋亡标志物（细胞色素c）和促凋亡因子（可溶性Fas配体）减少，抗凋亡因子（可溶性Fas）增加。观察到的性别差异与已知的性别在死亡率和发病率方面的差异一致。在另一个队列中，患有乳腺癌（n = 66）或前列腺癌（n = 38）的受试者，无论年龄大小，可溶性Fas均显著升高，可溶性Fas配体和总细胞色素c均降低。这些标志物与疾病严重程度相关，这与肿瘤对细胞凋亡的颠覆一致。正常受试者随着年龄增长整体细胞凋亡减少，这与病理生理学涉及细胞凋亡失调的疾病发病率增加一致。
