Immunosuppression Induced by Brain-Specific HDAC6 Knockdown Improves Aging Performance in Drosophila melanogaster

Yingying Zhao; Hongwen Xuan; Chao Shen; Peiyi Liu; Jing-Dong J Han; Wei Yu

doi:10.1007/s43657-022-00045-2

Immunosuppression Induced by Brain-Specific HDAC6 Knockdown Improves Aging Performance in Drosophila melanogaster

Phenomics. 2022 Feb 23;2(3):194-200. doi: 10.1007/s43657-022-00045-2. eCollection 2022 Jun.

Authors

Yingying Zhao^#¹, Hongwen Xuan^#², Chao Shen¹, Peiyi Liu¹, Jing-Dong J Han^{2

3}, Wei Yu¹

Affiliations

¹ State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, 200438 China.
² CAS Key Laboratory of Computational Biology, Shanghai Institutes for Biological Sciences, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031 China.
³ Peking-Tsinghua Center for Life Sciences, Center for Quantitative Biology (CQB), Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871 China.

^# Contributed equally.

Abstract

HDAC6 is involved in several biological processes related to aging-associated diseases. However, it was unknown whether HDAC6 could directly regulate lifespan and healthspan. We found that HDAC6 knockdown induced transcriptome changes to attenuate the aging changes in the Drosophila head, particularly on the inflammation and innate immunity-related genes. Whole-body knockdown of HDAC6 extended lifespan in the fly, furthermore brain-specific knockdown of HDAC6 extended both lifespan and healthspan in the fly. Our results established HDAC6 as a lifespan regulator and provided a potential anti-aging target.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00045-2.

Keywords: Aging; Drosophila; HDAC6; Inflammation; Innate immunity; Motor neuron.