Circadian Rhythm Disorder-Related Dysfunctions are Exacerbated by Aging and Ameliorated by Time-Restricted Feeding
Fengjiao Huo1 · Qing Liu1 · Shuaishuai Zhang1 · Xiaorui Liu1 · Shuyao Lv1 · Meili Zhao1 · Yue Liu1 · Xiaoqi Zhu1 · Ce Huang1 · Shengyu Feng1 · Hao Wang1 · Siling Xu1 · Junyan Shen1 · Jiaming Gao1 · Tingting Su2 · Yating Wu2 · Ruichan Jiang2 · Jian‑Kang Zhu3 · Hailiang Liu1,2,3
1 Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200123, China
2 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi 832003, China
3 Institute of Advanced Biotechnology and School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China
Abstract
Circadian rhythms are present in various species, and circadian rhythm disorder (CRD) affects people of all ages, especially those with age-related neurodegenerative diseases. Gut microbiota, which changes with age, also exhibits circadian rhythms. Disruption of gut microbial balance can trigger neurodegenerative diseases. This study explored the link between aging, CRD, and gut microbes by modeling CRD through light/dark cycle control. We found that aging worsened cognitive and mood disorders, along with gut microbial imbalance, intestinal barrier damage, and systemic inflammation in aged mice with CRD. Abnormal circadian gene expression increased oxidative stress. However, time-restricted feeding (TRF) improved CRD effects in aged mice by boosting Akkermansia muciniphila and inhibiting the NOD-like signaling pathway. This study shows that older mice exhibit increased behavioral and functional issues under CRD-related stress due to complex causes like systemic inflammation from a proinflammatory gut microbiome and oxidative stress from disrupted circadian genes. Maintaining a regular eating schedule significantly alleviates these CRD-induced issues in aged mice.
Keywords
Circadian Rhythm; Aging; Gut microbes; ROS; Time-restricted feeding
