A virus-acquired host cytokine controls systemic aging by antagonizing apoptosis
Aging is characterized by degeneration of unique tissues. However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model,...
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| Veröffentlicht in: | PLoS biology 2018-07, Vol.16 (7), p.e2005796 |
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| creator | Mlih, Mohamed Khericha, Mobina Birdwell, Christine West, A Phillip Karpac, Jason |
| description | Aging is characterized by degeneration of unique tissues. However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine-Diedel-that, when secreted from muscle or adipose, can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and regulate lifespan. Secreted homologs of Diedel are also found in viruses, having been acquired from host genomes. Focusing on potential mechanistic overlap between cellular aging and viral-host cell interactions, we found that Diedel is an inhibitor of apoptosis and can act as a systemic rheostat to modulate cell death during aging. These results highlight a key role for secreted antagonists of apoptosis in the systemic coordination of tissue aging. |
| doi_str_mv | 10.1371/journal.pbio.2005796 |
| format | Article |
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However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine-Diedel-that, when secreted from muscle or adipose, can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and regulate lifespan. Secreted homologs of Diedel are also found in viruses, having been acquired from host genomes. Focusing on potential mechanistic overlap between cellular aging and viral-host cell interactions, we found that Diedel is an inhibitor of apoptosis and can act as a systemic rheostat to modulate cell death during aging. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Mlih et al 2018 Mlih et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c695t-65022f55f97de70898723486dc649cfc565c2143ba395eccea198c8c1e5b69143</citedby><cites>FETCH-LOGICAL-c695t-65022f55f97de70898723486dc649cfc565c2143ba395eccea198c8c1e5b69143</cites><orcidid>0000-0003-3491-9616</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072105/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072105/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30036358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gould, Alex</contributor><creatorcontrib>Mlih, Mohamed</creatorcontrib><creatorcontrib>Khericha, Mobina</creatorcontrib><creatorcontrib>Birdwell, Christine</creatorcontrib><creatorcontrib>West, A Phillip</creatorcontrib><creatorcontrib>Karpac, Jason</creatorcontrib><title>A virus-acquired host cytokine controls systemic aging by antagonizing apoptosis</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>Aging is characterized by degeneration of unique tissues. However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine-Diedel-that, when secreted from muscle or adipose, can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and regulate lifespan. Secreted homologs of Diedel are also found in viruses, having been acquired from host genomes. Focusing on potential mechanistic overlap between cellular aging and viral-host cell interactions, we found that Diedel is an inhibitor of apoptosis and can act as a systemic rheostat to modulate cell death during aging. These results highlight a key role for secreted antagonists of apoptosis in the systemic coordination of tissue aging.</description><subject>Age</subject><subject>Aging</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>Antagonists</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Cell death</subject><subject>Cell interactions</subject><subject>Communication</subject><subject>Coordination</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Damage assessment</subject><subject>Degeneration</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>Drosophila</subject><subject>Drosophila melanogaster - cytology</subject><subject>Drosophila melanogaster - physiology</subject><subject>Drosophila Proteins - metabolism</subject><subject>Fruit flies</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Homeostasis</subject><subject>Homology</subject><subject>Hormesis</subject><subject>Host-virus relationships</subject><subject>Immunology</subject><subject>Insects</subject><subject>Intestine</subject><subject>Intestines</subject><subject>Life span</subject><subject>Longevity</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mitochondrial DNA</subject><subject>Muscles</subject><subject>Muscles - 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However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine-Diedel-that, when secreted from muscle or adipose, can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and regulate lifespan. Secreted homologs of Diedel are also found in viruses, having been acquired from host genomes. Focusing on potential mechanistic overlap between cellular aging and viral-host cell interactions, we found that Diedel is an inhibitor of apoptosis and can act as a systemic rheostat to modulate cell death during aging. These results highlight a key role for secreted antagonists of apoptosis in the systemic coordination of tissue aging.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30036358</pmid><doi>10.1371/journal.pbio.2005796</doi><orcidid>https://orcid.org/0000-0003-3491-9616</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Aging Aging - physiology Animals Antagonists Apoptosis Biology and Life Sciences Cell death Cell interactions Communication Coordination Cytokines Cytokines - metabolism Damage assessment Degeneration Deoxyribonucleic acid DNA DNA Damage Drosophila Drosophila melanogaster - cytology Drosophila melanogaster - physiology Drosophila Proteins - metabolism Fruit flies Gene expression Genetic aspects Genomes Homeostasis Homology Hormesis Host-virus relationships Immunology Insects Intestine Intestines Life span Longevity Medicine and Health Sciences Mice Mitochondrial DNA Muscles Muscles - metabolism Pathogenesis Physiological aspects Proteins Research and Analysis Methods Senescence Stem cells Stress response Tissue engineering Tissues Tumor necrosis factor-TNF Viruses Viruses - metabolism Zoological research |
| title | A virus-acquired host cytokine controls systemic aging by antagonizing apoptosis |
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