期刊
NATURE AGING
卷 2, 期 4, 页码 348-+出版社
SPRINGERNATURE
DOI: 10.1038/s43587-022-00198-9
关键词
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资金
- National Key Research and Development Program of China [2021YFC2009404, 2018YFC2002003, 2018YFC2002001, 2018YFC2002002, 2018YFC2002004, 2018YFC2002000]
- Natural Science Foundation of China [81971301, 32050410285, U1801285, 81973221, 81971327]
- Guangzhou Planned Project of Science and Technology [202002020039, 202102010030, 201904010111]
- Initial Supporting Foundation of Jinan University
- Milstein Medical Asian American Partnership (MMAAP) Foundation of the USA under the Irma and Paul Milstein Program for Senior Health
- China Pharmaceutical University 2020 Innovation and Entrepreneurship Elite Cultivation Plan
- Helse SOr-Ost [2017056, 2020001]
- Research Council of Norway [262175, 277813]
This study used single-cell RNA and TCR sequencing to analyze immune cells from different age groups and found that immune cells in frail older adults have distinct characteristics compared to healthy older adults and young individuals. The study identified transcription factors, clonotypes, and long noncoding RNAs associated with frailty.
Frailty is an intermediate status of the human aging process, associated with decompensated homeostasis and death. The immune phenotype of frailty and its underlying cellular and molecular processes remain poorly understood. We profiled 114,467 immune cells from cord blood, young adults and healthy and frail old adults using single-cell RNA and TCR sequencing. Here we show an age-dependent accumulation of transcriptome heterogeneity and variability in immune cells. Characteristic transcription factors were identified in given cell types of specific age groups. Trajectory analysis revealed cells from non-frail and frail old adults often fall into distinct paths. Numerous TCR clonotypes were shared among T-cell subtypes in old adults, indicating differential pluripotency and resilience capabilities of aged T cells. A frailty-specific monocyte subset was identified with exclusively high expression of long noncoding RNAs NEAT1 and MALAT1. Our study discovers human frailty-specific immune cell characteristics based on the comprehensive dimensions in the immune landscape of aging and frailty.
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