| 项目编号 |
PRJCA025375 |
| 项目标题 |
Recovering matrikine-induced immune dysfunction extends health- and lifespan |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
CyTOF
|
| 物种名称 |
Mus musculus
|
| 描述信息 |
This study investigates the effects of age-related pathological remodeling of the extracellular matrix and its matrix-derived fragments, known as matrikines. We specifically found that elastin-derived fragments (ELN fragments) are strongly correlated with aging and a reduction in lifespan. Mechanistically, the VGVAPG oligopeptide within ELN fragments activates macrophages and monocytes via the transmembrane protein NEU1, leading to prolonged lymphocyte dysfunction and chronic inflammation. Therapeutically, a NEU1 inhibitor was shown to extend the health and lifespan of naturally-aged wild-type mice. Additionally, we confirmed in a human cohort of 1068 samples that serum ELN fragments correlate with aging indicators, and demonstrated in pig and immune-humanized mouse models that the NEU1 inhibitor can reverse the aging indicators induced by ELN fragments. This research provides new insights into matrikine-induced aging, unveils the underlying immunological mechanisms, and proposes a novel direction for aging intervention by targeting matrikine signaling. |
| 样品范围 |
Monoisolate |
| 发布日期 |
2025-07-15 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 41023316
|
Elastin-derived extracellular matrix fragments drive aging through innate immune activation
|
Nature Aging
|
10.1038/s43587-025-00961-8
|
2025
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
Science Fund for Creative Research Groups
|
T2121004
|
|
|
|
| 提交者 |
Hongwei
Ouyang (hwoy@zju.edu.cn)
|
| 提交单位 |
Zhejiang University |
| 提交日期 |
2024-04-17 |
