Jones Christopher M, Boelaert Kristien
Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
Gerontology. 2015;61(4):291-300. doi: 10.1159/000367692. Epub 2014 Nov 27.
Significant advances in health and social wellbeing have led to linear gains in life expectancy and an accompanying increase in the burden imposed by age-related morbidities. Complex alterations in hormonal networks which regulate homeostasis and survival may underlie this poor adaptation to later life, as exemplified by an increased fracture risk amongst post-menopausal women. Beyond overt under- or overactivity of hormonal axes, changes in the concentrations of regulatory hormones may also impact on health and disease. Subclinical hyperthyroidism, a disorder characterised by normal thyroxine levels in the presence of decreased thyroid-stimulating hormone, is, for instance, independently associated with an increased risk of atrial fibrillation amongst elderly populations. Both the menopause and subclinical thyroid disease demonstrate the difficulty in reversing endocrine changes in later life, with minimal impact from thyroxine therapy in subclinical hypothyroidism and multiple reports of harm resulting from hormone replacement therapy in peri- and post-menopausal women. Given these findings, strategies to locally regulate hormone bioavailability by altering pre-receptor metabolism may offer greater therapeutic potential in the fight against age-related disease. This review aims to provide an overview of the ageing endocrine system and its potential impact on health and disease in the elderly. It will postulate that strategies to coordinate pre-receptor hormone metabolism and a greater understanding of putative hormonal longevity pathways may offer key new drug targets in the fight against ageing, and will argue against applying the conventional endocrine maxim of 'block and replace' to hormonal changes seen during ageing.
健康和社会福祉方面的重大进步使预期寿命直线上升，同时与年龄相关的发病率所带来的负担也随之增加。调节体内平衡和生存的激素网络发生复杂变化，可能是导致对晚年适应不良的原因，绝经后女性骨折风险增加就是一个例证。除了激素轴明显的功能减退或亢进外，调节激素浓度的变化也可能影响健康和疾病。例如，亚临床甲状腺功能亢进是一种在甲状腺刺激激素降低的情况下甲状腺素水平正常的疾病，它与老年人群中心房颤动风险增加独立相关。绝经和亚临床甲状腺疾病都表明，在晚年逆转内分泌变化存在困难，亚临床甲状腺功能减退症患者接受甲状腺素治疗的效果甚微，而关于围绝经期和绝经后女性激素替代疗法造成伤害的报道屡见不鲜。鉴于这些发现，通过改变受体前代谢来局部调节激素生物利用度的策略，可能在对抗与年龄相关的疾病方面具有更大的治疗潜力。本综述旨在概述衰老的内分泌系统及其对老年人健康和疾病的潜在影响。文章将假定，协调受体前激素代谢的策略以及对假定的激素长寿途径的更深入理解，可能为对抗衰老提供关键的新药物靶点，并反对将传统的“阻断并替代”内分泌原则应用于衰老过程中出现的激素变化。
