Aulinas Anna, Ramírez María José, Barahona María José, Mato Eugènia, Bell Olga, Surrallés Jordi, Webb Susan M
Biomedical Research Institute Sant Pau (IIB Sant Pau), Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Clin Endocrinol (Oxf). 2013 Dec;79(6):751-9. doi: 10.1111/cen.12310. Epub 2013 Sep 4.
Telomeres, located at the end of linear chromosomes, are essential to maintain genomic stability. Telomere biology has recently emerged as an important player in the fields of ageing and disease. To maintain telomere length (TL) and reduce its degradation after mitosis, the telomerase enzyme complex is produced. Genetic, epigenetic, hormonal and environmental factors can regulate telomerase function. These include stress hormones such as cortisol and growth factors. The hypothalamic-pituitary-adrenal (HPA) axis has been evaluated in psychiatric diseases where hypercortisolism and oxidative stress are often present. Some researches have linked TL shortening to increases in stress-related cortisol, but others have not. The effects of cortisol on the telomere system are complex and may depend on the intensity and duration of exposure. On the other hand, low levels of IGF-1 are associated with inflammation and ageing-related diseases (ischaemic heart disease, congestive heart failure). Both IGF-1 and TL diminish with age and are positively and strongly correlated with each other. It is not clear whether this positive correlation reflects a single association or a cause-effect relationship. Further research will ideally investigate longitudinal changes in telomeres and both these hormonal axes. To our knowledge, TL dysfunction has not been described in either endogenous hypercortisolism (Cushing's syndrome) or acromegaly where excessive amounts of GH and consequently IGF-1 are produced. This review focuses on the possible relationships between telomere dysfunction and the hypothalamic-pituitary-adrenal (HPA) axis and GH-IGF-1 system.
端粒位于线性染色体末端，对于维持基因组稳定性至关重要。端粒生物学最近成为衰老和疾病领域的一个重要因素。为了维持端粒长度（TL）并减少有丝分裂后端粒的降解，端粒酶复合物得以产生。遗传、表观遗传、激素和环境因素可调节端粒酶功能。这些因素包括皮质醇等应激激素和生长因子。下丘脑 - 垂体 - 肾上腺（HPA）轴已在常伴有高皮质醇血症和氧化应激的精神疾病中得到评估。一些研究将端粒缩短与应激相关皮质醇的增加联系起来，但其他研究则未发现这种关联。皮质醇对端粒系统的影响很复杂，可能取决于暴露的强度和持续时间。另一方面，低水平的胰岛素样生长因子 -1（IGF -1）与炎症及衰老相关疾病（缺血性心脏病、充血性心力衰竭）有关。IGF -1和端粒长度均随年龄增长而减少，且二者呈显著正相关。目前尚不清楚这种正相关反映的是单一关联还是因果关系。理想情况下，进一步的研究将调查端粒的纵向变化以及这两个激素轴。据我们所知，在内源性高皮质醇血症（库欣综合征）或肢端肥大症（会产生过量生长激素及由此产生过量IGF -1）中，尚未描述端粒功能障碍。本综述重点关注端粒功能障碍与下丘脑 - 垂体 - 肾上腺（HPA）轴及生长激素 - 胰岛素样生长因子 -1（GH - IGF -1）系统之间的可能关系。
