Department of Clinical Biochemistry, Biomedicine Institute of Seville/CSIC, University of Seville, Virgen del Rocío University Hospital, Manuel Siurot Street, s/n, 41013 Seville, Spain.
Exp Gerontol. 2009 May;44(5):328-34. doi: 10.1016/j.exger.2009.02.002. Epub 2009 Feb 20.
In the search of new therapeutic targets improving the quality of life of elderly, melatonin, "the chemical expression of darkness", seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and anti-aging properties. The present study was designed to elucidate effects of aging in melatonin extrapineal synthesis and investigate evident age-related alterations in the action mechanisms involved. The presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was analyzed in thymus, spleen, liver, kidney and heart of 3- and 12month-old rats using real time PCR as well as its functionality by enzymatic activity assays. In addition, extrapineal melatonin content was measured by a competitive enzyme immunoassay (ELISA). The results of this study reveal that all rat tissues studied including thymus, and for the first time, spleen, liver, kidney and heart have the necessary machinery to synthesize melatonin. Moreover, we report an age-related decline in rat extrapineal melatonin synthesis with a consequent HIOMT functionality decrease in spleen, liver and heart during physiological aging. On the contrary, NAT enzymatic activity maintains unchanged without evident alterations with advancing age. Moreover, diminished melatonin concentrations were measured in these tissues cited above during aging except in the thymus, where, surprisingly, melatonin content, NAT/HIOMT expression, and enzymatic functionality assays revealed no significant alterations with age. As a conclusion, we report evident age-related changes in melatonin synthesis in some rat peripheral organs. We suggest that thymus may develop compensatory mechanisms to counteract the loss of immune activity and consequently, the loss of this potent antioxidant, during physiological aging.
在寻找改善老年人生活质量的新治疗靶点的过程中，褪黑素——“黑暗的化学表达”，由于其抗氧化、免疫增强和抗衰老特性，似乎在衰老过程中发挥着显著的作用。本研究旨在阐明衰老对褪黑素松果体外合成的影响，并研究涉及的作用机制中明显的与年龄相关的变化。使用实时 PCR 分析 3 个月和 12 个月大的大鼠胸腺、脾、肝、肾和心脏中参与褪黑素合成的两种关键酶，芳香族烷基胺-N-乙酰转移酶（AA-NAT）和羟基吲哚-O-甲基转移酶（HIOMT）的存在，以及通过酶活性测定分析其功能。此外，通过竞争性酶免疫测定（ELISA）测量松果体外褪黑素含量。这项研究的结果表明，所有研究的大鼠组织，包括胸腺，以及首次报道的脾、肝、肾和心脏，都具有合成褪黑素的必要机制。此外，我们报告了与年龄相关的大鼠松果体外褪黑素合成下降，伴随着生理衰老过程中脾、肝和心脏中 HIOMT 功能下降。相反，NAT 酶活性保持不变，没有明显的随年龄增长而变化。此外，在上述组织中测量到褪黑素浓度随年龄的降低，除了胸腺，令人惊讶的是，在胸腺中，褪黑素含量、NAT/HIOMT 表达和酶功能测定显示与年龄无关。总之，我们报告了一些大鼠外周器官中褪黑素合成与年龄相关的明显变化。我们认为，胸腺可能会发展出补偿机制，以对抗生理衰老过程中免疫活性的丧失，以及这种强效抗氧化剂的丧失。
