| RRC ID |
80885
|
| 著者 |
Hu Z, Luo Y, Liu Y, Luo Y, Wang L, Gou S, Peng Y, Wei R, Jia D, Wang Y, Gao S, Zhang Y.
|
| タイトル |
Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span.
|
| ジャーナル |
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.
|
| 巻・号 |
21(7)
|
| ページ |
e3002165
|
| 公開日 |
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*
|
| リソース情報 |
| 線虫 |
tm3425 |
