Aging Triggers an Intestinal Energy Crisis and HDL3 Deficiency Disrupting Gut-Liver Axis Homeostasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41851037.
- Also identified by DOI 10.1111/acel.70445 and PMC identifier 13093439.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
During aging, decreased intestinal barrier function and its ability to synthesize metabolites are closely associated with various age-related diseases. However, the mechanism by which impaired intestinal synthesis contributes to gut-liver axis aging remains unclear. This study reveals that aging induces a mitochondrial energy crisis and defective membrane localization of ABCA1, significantly inhibiting the biosynthesis of high-density lipoprotein 3 (HDL3) in the intestine. Exogenous supplementation with β-nicotinamide mononucleotide (NMN) restores intestinal NAD<sup>+</sup> homeostasis, enhances oxidative phosphorylation efficiency, and promotes ATP-dependent lipid transport, thereby rejuvenating the production of gut-derived HDL3. Further investigations demonstrate that gut-originated HDL3 neutralizes lipopolysaccharide (LPS) in the liver and attenuates TLR4-mediated inflammatory cascades, ultimately ameliorating age-related liver injury. These findings elucidate a novel mechanism whereby NMN modulates the NAD<sup>+</sup>-mitochondria-ABCA1-HDL3 axis to preserve gut-liver axis function, offering a promising therapeutic strategy for mitigating aging-related pathologies in this metabolic cross-talk.
Medical subject headings
- Liver
- Homeostasis
- Aging
- Intestines
- Energy Metabolism
- Intestinal Mucosa
- Lipoproteins, HDL