| RRC ID |
53533
|
| Author |
Seah NE, de Magalhaes Filho CD, Petrashen AP, Henderson HR, Laguer J, Gonzalez J, Dillin A, Hansen M, Lapierre LR.
|
| Title |
Autophagy-mediated longevity is modulated by lipoprotein biogenesis.
|
| Journal |
Autophagy
|
| Abstract |
Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis.
|
| Volume |
12(2)
|
| Pages |
261-72
|
| Published |
2016-1-1
|
| DOI |
10.1080/15548627.2015.1127464
|
| PMID |
26671266
|
| PMC |
PMC4836030
|
| MeSH |
Animals
Autophagy*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / physiology*
Caenorhabditis elegans Proteins / metabolism
Caloric Restriction
Gene Expression Regulation
Gene Silencing
Intestinal Mucosa / metabolism
Lipase / metabolism
Lipolysis
Lipoproteins / biosynthesis*
Longevity / physiology*
Lysosomes / metabolism
Transcription, Genetic
Vitellogenesis / genetics
Vitellogenins / metabolism
|
| IF |
11.059
|
| Times Cited |
43
|
| Resource |
| C.elegans |
tm1011
tm4498
tm4417
tm1978 |
