Lim Jin Ju, Hyun Seogang
Department of Life Science, Chung-Ang University, Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
Department of Life Science, Chung-Ang University, Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
Biomed Pharmacother. 2022 May;149:112803. doi: 10.1016/j.biopha.2022.112803. Epub 2022 Mar 11.
Minocycline is a semi-synthetic tetracycline derivative antibiotic that has been examined for its non-antibiotic properties, such as anti-inflammatory, tumor-suppressive, and neuroprotective effects. In this study, we found that feeding minocycline to Drosophila improves proteostasis during organismal aging. Poly-ubiquitinated protein aggregates increase in the flight muscles as flies age, which are reduced in response to minocycline feeding. Minocycline feeding increases the expression of several autophagy genes and the activity of the autophagy/lysosomal pathway in Drosophila muscles. Interestingly, mutant flies lacking either FOXO or Hsp70 showed increased levels of poly-ubiquitinated protein aggregates with reduced autophagy/lysosomal activity, which was not reversed by minocycline feeding. Our findings suggest that minocycline may improve proteostasis in aging tissues via FOXO-Hsp70 axis, which highlights the multifaceted effects of minocycline as a therapeutic agent in age-associated features.
米诺环素是一种半合成四环素衍生物抗生素，人们已对其非抗生素特性进行了研究，如抗炎、肿瘤抑制和神经保护作用。在本研究中，我们发现给果蝇喂食米诺环素可改善机体衰老过程中的蛋白质稳态。随着果蝇衰老，飞行肌中多泛素化蛋白聚集体增加，而喂食米诺环素可使其减少。喂食米诺环素可增加果蝇肌肉中几种自噬基因的表达以及自噬/溶酶体途径的活性。有趣的是，缺乏FOXO或Hsp70的突变果蝇显示多泛素化蛋白聚集体水平增加，自噬/溶酶体活性降低，喂食米诺环素并不能逆转这种情况。我们的研究结果表明，米诺环素可能通过FOXO - Hsp70轴改善衰老组织中的蛋白质稳态，这突出了米诺环素作为治疗剂在与年龄相关特征方面的多方面作用。
