Adiponectin deficiency accelerates brain aging via mitochondria-associated neuroinflammation

He, Kaiwu1,2; Nie, Lulin2; Ali, Tahir1; Liu, Zizhen1; Li, Weifen1; Gao, Ruyan1; Zhang, Zena2; Liu, Jianjun2; Dai, Zhongliang3,4,5; Xie, Yongmei6,7,8; Zhang, Zaijun9; Liu, Gongping10; Dong, Ming11; Yu, Zhi-Jian12,13; Li, Shupeng1,14,15; Yang, Xifei2

2023-04-01

10.1186/s12979-023-00339-7

IMMUNITY & AGEING   Impact Factor & Quartile

1742-4933

BackgroundA wide spectrum of changes occurs in the brain with age, from molecular to morphological aspects, and inflammation accompanied by mitochondria dysfunction is one of the significant factors associated with age. Adiponectin (APN), an essential adipokine in glucose and lipid metabolism, is involved in the aging; however, its role in brain aging has not been adequately explored. Here, we aimed to explore the relationship between APN deficiency and brain aging using multiple biochemical and pharmacological methods to probe APN in humans, KO mice, primary microglia, and BV2 cells.ResultsWe found that declining APN levels in aged human subjects correlated with dysregulated cytokine levels, while APN KO mice exhibited accelerated aging accompanied by learning and memory deficits, anxiety-like behaviors, neuroinflammation, and immunosenescence. APN-deficient mice displayed aggravated mitochondrial dysfunction and HDAC1 upregulation. In BV2 cells, the APN receptor agonist AdipoRon alleviated the mitochondrial deficits and aging markers induced by rotenone or antimycin A. HDAC1 antagonism by Compound 60 (Cpd 60) improved mitochondrial dysfunction and age-related inflammation, as validated in D-galactose-treated APN KO mice.ConclusionThese findings indicate that APN is a critical regulator of brain aging by preventing neuroinflammation associated with mitochondrial impairment via HDAC1 signaling.

Adiponectin Aging HDAC1 Neuroinflammation Mitochondria BV2 Cells

SCI

English

Others

National Natural Science Foundation of China (NSFC)["81673134","81171191","82171583"] ; Shenzhen-Hong Kong Institute of Brain Science["2019SHIBS0004","NYKFKT20190019"] ; Sanming Project of Medicine in Shenzhen[SZSM201611090] ; Shenzhen Key Medical Discipline Construction Fund[SZXK069] ; Key Basic Research Program of Shenzhen Science and Technology Innovation Commission["JCYJ20200109150717745","JCYJ20200109144418639"]

Geriatrics & Gerontology ; Immunology

Geriatrics & Gerontology ; Immunology

WOS:000961774800001

BMC

Web of Science

1.Peking Univ, Sch Chem Biol & Biotechnol, State Key Lab Oncogen, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China
2.Shenzhen Ctr Dis Control & Prevent, Shenzhen Key Lab Modern Toxicol, Shenzhen Med Key Discipline Hlth Toxicol 2020 2024, Shenzhen 518055, Peoples R China
3.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Anesthesiol, Shenzhen 518020, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Dept Anesthesiol, Shenzhen 518020, Guangdong, Peoples R China
5.Shenzhen Engn Res Ctr Anesthesiol, Shenzhen 518020, Guangdong, Peoples R China
6.Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China
7.Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China
8.Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China
9.Jinan Univ, Inst New Drug Res, Coll Pharm, Guangzhou 510632, Peoples R China
10.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathophysiol,Key Lab,Minist Educ China & Hube, Wuhan, Peoples R China
11.Guangzhou Int Bio Isl, Guangzhou 510005, Guangdong, Peoples R China
12.Shenzhen Univ, Affiliated Hosp 6, Hlth Sci Ctr, Dept Infect Dis, 89 Taoyuan Rd, Shenzhen 518052, Peoples R China
13.Shenzhen Univ, Affiliated Hosp 6, Hlth Sci Ctr, Shenzhen Key Lab Endogenous Infect, 89 Taoyuan Rd, Shenzhen 518052, Peoples R China
14.Campbell Res Inst, Ctr Addict & Mental Hlth, Toronto, ON, Canada
15.Univ Toronto, Dept Psychiat, Toronto, ON, Canada

He, Kaiwu,Nie, Lulin,Ali, Tahir,et al. Adiponectin deficiency accelerates brain aging via mitochondria-associated neuroinflammation[J]. IMMUNITY & AGEING,2023,20(1).

He, Kaiwu.,Nie, Lulin.,Ali, Tahir.,Liu, Zizhen.,Li, Weifen.,...&Yang, Xifei.(2023).Adiponectin deficiency accelerates brain aging via mitochondria-associated neuroinflammation.IMMUNITY & AGEING,20(1).

He, Kaiwu,et al."Adiponectin deficiency accelerates brain aging via mitochondria-associated neuroinflammation".IMMUNITY & AGEING 20.1(2023).