Reference - Detail
| RRC ID | 80885 |
|---|---|
| Author | Hu Z, Luo Y, Liu Y, Luo Y, Wang L, Gou S, Peng Y, Wei R, Jia D, Wang Y, Gao S, Zhang Y. |
| Title | Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span. |
| Journal | PLoS Biol |
| Abstract |
Global increase of life expectancy is rarely accompanied by increased health span, calling for a greater understanding of age-associated behavioral decline. Motor independence is strongly associated with the quality of life of elderly people, yet the regulators for motor aging have not been systematically explored. Here, we designed a fast and efficient genome-wide screening assay in Caenorhabditis elegans and identified 34 consistent genes as potential regulators of motor aging. Among the top hits, we found VPS-34, the class III phosphatidylinositol 3-kinase that phosphorylates phosphatidylinositol (PI) to phosphatidylinositol 3-phosphate (PI(3)P), regulates motor function in aged but not young worms. It primarily functions in aged motor neurons by inhibiting PI(3)P-PI-PI(4)P conversion to reduce neurotransmission at the neuromuscular junction (NMJ). Genetic and pharmacological inhibition of VPS-34 improve neurotransmission and muscle integrity, ameliorating motor aging in both worms and mice. Thus, our genome-wide screening revealed an evolutionarily conserved, actionable target to delay motor aging and prolong health span. |
| Volume | 21(7) |
| Pages | e3002165 |
| Published | 2023-7-1 |
| DOI | 10.1371/journal.pbio.3002165 |
| PII | PBIOLOGY-D-22-02899 |
| PMID | 37432924 |
| PMC | PMC10335676 |
| MeSH | Aging Animals Caenorhabditis elegans / genetics Inhibition, Psychological Mice Phosphatidylinositol 3-Kinases* Quality of Life* |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 23 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm3425 |