Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans.
The normal aging process is associated with stereotyped changes in gene expression, but the regulators responsible for these age-dependent changes are poorly understood. Using a novel genomics approach, we identified HOX co-factor unc-62 (Homothorax) as a developmental regulator that binds proximal...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3585033?pdf=render |
| _version_ | 1818478177360543744 |
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| author | Eric L Van Nostrand Adolfo Sánchez-Blanco Beijing Wu Andy Nguyen Stuart K Kim |
| author_facet | Eric L Van Nostrand Adolfo Sánchez-Blanco Beijing Wu Andy Nguyen Stuart K Kim |
| author_sort | Eric L Van Nostrand |
| collection | DOAJ |
| description | The normal aging process is associated with stereotyped changes in gene expression, but the regulators responsible for these age-dependent changes are poorly understood. Using a novel genomics approach, we identified HOX co-factor unc-62 (Homothorax) as a developmental regulator that binds proximal to age-regulated genes and modulates lifespan. Although unc-62 is expressed in diverse tissues, its functions in the intestine play a particularly important role in modulating lifespan, as intestine-specific knockdown of unc-62 by RNAi increases lifespan. An alternatively-spliced, tissue-specific isoform of unc-62 is expressed exclusively in the intestine and declines with age. Through analysis of the downstream consequences of unc-62 knockdown, we identify multiple effects linked to aging. First, unc-62 RNAi decreases the expression of yolk proteins (vitellogenins) that aggregate in the body cavity in old age. Second, unc-62 RNAi results in a broad increase in expression of intestinal genes that typically decrease expression with age, suggesting that unc-62 activity balances intestinal resource allocation between yolk protein expression and fertility on the one hand and somatic functions on the other. Finally, in old age, the intestine shows increased expression of several aberrant genes; these UNC-62 targets are expressed predominantly in neuronal cells in developing animals, but surprisingly show increased expression in the intestine of old animals. Intestinal expression of some of these genes during aging is detrimental for longevity; notably, increased expression of insulin ins-7 limits lifespan by repressing activity of insulin pathway response factor DAF-16/FOXO in aged animals. These results illustrate how unc-62 regulation of intestinal gene expression is responsible for limiting lifespan during the normal aging process. |
| first_indexed | 2024-12-10T09:45:05Z |
| format | Article |
| id | doaj.art-f783843de7094c4895ebf14d3027db8d |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-10T09:45:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-f783843de7094c4895ebf14d3027db8d2022-12-22T01:53:53ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0192e100332510.1371/journal.pgen.1003325Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans.Eric L Van NostrandAdolfo Sánchez-BlancoBeijing WuAndy NguyenStuart K KimThe normal aging process is associated with stereotyped changes in gene expression, but the regulators responsible for these age-dependent changes are poorly understood. Using a novel genomics approach, we identified HOX co-factor unc-62 (Homothorax) as a developmental regulator that binds proximal to age-regulated genes and modulates lifespan. Although unc-62 is expressed in diverse tissues, its functions in the intestine play a particularly important role in modulating lifespan, as intestine-specific knockdown of unc-62 by RNAi increases lifespan. An alternatively-spliced, tissue-specific isoform of unc-62 is expressed exclusively in the intestine and declines with age. Through analysis of the downstream consequences of unc-62 knockdown, we identify multiple effects linked to aging. First, unc-62 RNAi decreases the expression of yolk proteins (vitellogenins) that aggregate in the body cavity in old age. Second, unc-62 RNAi results in a broad increase in expression of intestinal genes that typically decrease expression with age, suggesting that unc-62 activity balances intestinal resource allocation between yolk protein expression and fertility on the one hand and somatic functions on the other. Finally, in old age, the intestine shows increased expression of several aberrant genes; these UNC-62 targets are expressed predominantly in neuronal cells in developing animals, but surprisingly show increased expression in the intestine of old animals. Intestinal expression of some of these genes during aging is detrimental for longevity; notably, increased expression of insulin ins-7 limits lifespan by repressing activity of insulin pathway response factor DAF-16/FOXO in aged animals. These results illustrate how unc-62 regulation of intestinal gene expression is responsible for limiting lifespan during the normal aging process.http://europepmc.org/articles/PMC3585033?pdf=render |
| spellingShingle | Eric L Van Nostrand Adolfo Sánchez-Blanco Beijing Wu Andy Nguyen Stuart K Kim Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans. PLoS Genetics |
| title | Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans. |
| title_full | Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans. |
| title_fullStr | Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans. |
| title_full_unstemmed | Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans. |
| title_short | Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans. |
| title_sort | roles of the developmental regulator unc 62 homothorax in limiting longevity in caenorhabditis elegans |
| url | http://europepmc.org/articles/PMC3585033?pdf=render |
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