The University of Manchester, A V Hill Building, Manchester, UK.
Biogerontology. 2012 Feb;13(1):3-20. doi: 10.1007/s10522-011-9322-y. Epub 2011 Mar 3.
The links between hormonal signalling and lifespan have been well documented in a range of model organisms. For example, in C. elegans or D. melanogaster, lifespan can be modulated by ablating germline cells, or manipulating reproductive history or pregnenolone signalling. In mammalian systems, however, hormonal contribution to longevity is less well understood. With increasing age human steroid hormone profiles change substantially, particularly following menopause in women. This article reviews recent links between steroid sex hormones and ageing, with special emphasis on the skin and wound repair. Estrogen, which substantially decreases with advancing age in both males and females, protects against multiple aspects of cellular ageing in rodent models, including oxidative damage, telomere shortening and cellular senescence. Estrogen's effects are particularly pronounced in the skin where cutaneous changes post-menopause are well documented, and can be partially reversed by classical Hormone Replacement Therapy (HRT). Our research shows that while chronological ageing has clear effects on skin wound healing, falling estrogen levels are the principle mediator of these effects. Thus, both HRT and topical estrogen replacement substantially accelerate healing in elderly humans, but are associated with unwanted deleterious effects, particularly cancer promotion. In fact, much current research effort is being invested in exploring the therapeutic potential of estrogen signalling manipulation to reverse age-associated pathology in peripheral tissues. In the case of the skin the differential targeting of estrogen receptors to promote healing in aged subjects is a real therapeutic possibility.
激素信号与寿命之间的联系在一系列模式生物中已有充分的记录。例如，在秀丽隐杆线虫或黑腹果蝇中，通过消融生殖细胞、操纵生殖史或孕烯醇酮信号，可以调节寿命。然而，在哺乳动物系统中，激素对长寿的贡献还不太清楚。随着年龄的增长，人类类固醇激素谱发生了很大变化，特别是在女性绝经后。本文综述了类固醇性激素与衰老之间的最新联系，特别强调了皮肤和伤口修复。雌激素在男性和女性中随着年龄的增长而显著下降，可保护啮齿动物模型中细胞衰老的多个方面，包括氧化损伤、端粒缩短和细胞衰老。雌激素的作用在皮肤中尤为明显，绝经后皮肤的变化已有充分的记录，并且可以部分通过经典的激素替代疗法（HRT）逆转。我们的研究表明，虽然时间性衰老对皮肤伤口愈合有明显影响，但雌激素水平下降是这些影响的主要介导因素。因此，HRT 和局部雌激素替代都能显著加速老年人的伤口愈合，但与不想要的有害作用有关，特别是促进癌症。事实上，目前正在投入大量研究努力探索雌激素信号转导操纵的治疗潜力，以逆转周围组织与年龄相关的病理学。就皮肤而言，将雌激素受体靶向特定组织以促进老年患者的愈合是一种真正的治疗可能性。
