ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target
- Publication Date
- September 25, 2012
- Journal
- PLOS ONE
- Authors
- Yongsoon Kim & Hong Sun
- Volume
- 7
- Issue
- 9
- Pages
- e45890
- DOI
- https://dx.plos.org/10.1371/journal.pone.0045890
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0045890
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/23049887
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457945
- Europe PMC
- http://europepmc.org/abstract/MED/23049887
- Web of Science
- 000309556100097
- Scopus
- 84866661779
- Mendeley
- http://www.mendeley.com/research/asm3-acid-sphingomyelinase-functions-positive-regulator-daf2age1-signaling-pathway-serves-novel-anti
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Mendeley | Further Information
{"title"=>"ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target", "type"=>"journal", "authors"=>[{"first_name"=>"Yongsoon", "last_name"=>"Kim", "scopus_author_id"=>"55934221300"}, {"first_name"=>"Hong", "last_name"=>"Sun", "scopus_author_id"=>"57191822205"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84866661779", "pmid"=>"23049887", "doi"=>"10.1371/journal.pone.0045890", "pui"=>"365720724", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "scopus"=>"2-s2.0-84866661779"}, "id"=>"fc8ecfb9-f697-3b5b-bca6-60ba6787fa84", "abstract"=>"In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.", "link"=>"http://www.mendeley.com/research/asm3-acid-sphingomyelinase-functions-positive-regulator-daf2age1-signaling-pathway-serves-novel-anti", "reader_count"=>35, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>1, "Student > Bachelor"=>7, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>1, "Student > Bachelor"=>7, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>24}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"United States"=>3}, "group_count"=>1}CrossRef
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Europe PMC Database Citations | Further Information
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Relative Metric
{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[313, 562, 690, 796, 893, 986, 1079, 1173, 1257, 1349, 1429, 1506, 1586, 1661, 1730, 1803, 1876, 1945, 2017, 2091, 2163, 2225, 2294, 2362, 2430]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[333, 576, 707, 814, 908, 1004, 1104, 1197, 1280, 1370, 1449, 1531, 1603, 1673, 1742, 1817, 1886, 1954, 2025, 2098, 2171, 2234, 2304, 2365, 2431]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[324, 551, 679, 782, 879, 971, 1064, 1154, 1245, 1328, 1406, 1476, 1541, 1617, 1683, 1754, 1818, 1893, 1962, 2025, 2092, 2164, 2227, 2294, 2355]}]}Loading … 

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