publication . Article . 2017

Anti‐inflammaging effects of human alpha‐1 antitrypsin

Yuan, Ye; DiCiaccio, Benedetto; Li, Ying; Elshikha, Ahmed S.; Titov, Denis; Brenner, Brian; Seifer, Lee; Pan, Hope; Karic, Nurdina; Akbar, Mohammad A.; ...
Open Access English
  • Published: 01 Oct 2017 Journal: Aging Cell, volume 17, issue 1 (issn: 1474-9718, eissn: 1474-9726, Copyright policy)
  • Publisher: John Wiley and Sons Inc.
Abstract
Summary Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism ...
Subjects
free text keywords: Original Article, inflammaging, Drosophila, NF‐κB, innate immune response, human alpha‐1 antitrypsin, Original Articles, senescence‐associated secretory phenotype
Related Organizations
Funded by
NIH| Rapid Induction of apoptosis against viral infection
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01GM106174-01A1
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
45 references, page 1 of 3

Akbar MA, Cao JJ, Lu Y, Nardo D, Chen MJ, Elshikha AS, Ahamed R, Brantly M, Holliday LS, Song S (2016) Alpha‐1 antitrypsin gene therapy ameliorates bone loss in ovariectomy‐induced osteoporosis mouse model. Hum. Gene Ther. 27, 679–686.27158796 [PubMed]

Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol. 11, R106.20979621 [OpenAIRE] [PubMed]

Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM (2016) Naturally occurring p16(Ink4a)‐positive cells shorten healthy lifespan. Nature 530, 184–189.26840489 [OpenAIRE] [PubMed]

Blice‐Baum AC, Zambon AC, Kaushik G, Viswanathan MC, Engler AJ, Bodmer R, Cammarato A (2017) Modest overexpression of FOXO maintains cardiac proteostasis and ameliorates age‐associated functional decline. Aging Cell 16, 93–103.28090761 [OpenAIRE] [PubMed]

Buchon N, Silverman N, Cherry S (2014) Immunity in Drosophila melanogaster – from microbial recognition to whole‐organism physiology. Nat. Rev. Immunol. 14, 796–810.25421701 [OpenAIRE] [PubMed]

Cao JJ, Gregoire BR, Sun L, Song S (2011) Alpha‐1 antitrypsin reduces ovariectomy‐induced bone loss in mice. Ann. N. Y. Acad. Sci. 1240, E31–E35.22360827 [PubMed]

Churg A, Wang X, Wang RD, Meixner SC, Pryzdial EL, Wright JL (2007) Alpha1‐antitrypsin suppresses TNF‐alpha and MMP‐12 production by cigarette smoke‐stimulated macrophages. Am. J. Respir. Cell Mol. Biol. 37, 144–151.17395890 [PubMed]

Contrepois K, Coudereau C, Benayoun BA, Schuler N, Roux PF, Bischof O, Courbeyrette R, Carvalho C, Thuret JY, Ma Z, Derbois C, Nevers MC, Volland H, Redon CE, Bonner WM, Deleuze JF, Wiel C, Bernard D, Snyder MP, Rube CE, Olaso R, Fenaille F, Mann C (2017) Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression. Nat. Commun. 8, 14995.28489069 [OpenAIRE] [PubMed]

Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J (2008) Senescence‐associated secretory phenotypes reveal cell‐nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853–2868.19053174 [OpenAIRE] [PubMed]

Coppe JP, Desprez PY, Krtolica A, Campisi J (2010) The senescence‐associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118.20078217 [OpenAIRE] [PubMed]

Elshikha AS, Lu Y, Chen MJ, Akbar M, Zeumer L, Ritter A, Elghamry H, Mahdi MA, Morel L, Song S (2016) Alpha 1 antitrypsin inhibits dendritic cell activation and attenuates nephritis in a mouse model of lupus. PLoS ONE 11, e0156583.27232337 [OpenAIRE] [PubMed]

Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr. Rev. 65, S173–S176.18240544 [PubMed]

Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age‐associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69(Suppl 1), S4–S9.24833586 [PubMed]

Freund A, Patil CK, Campisi J (2011) p38MAPK is a novel DNA damage response‐independent regulator of the senescence‐associated secretory phenotype. EMBO J. 30, 1536–1548.21399611 [OpenAIRE] [PubMed]

Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Dechanet‐Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B (2017) Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat. Med. 23, 174–184.28092664 [OpenAIRE] [PubMed]

45 references, page 1 of 3
Abstract
Summary Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism ...
Subjects
free text keywords: Original Article, inflammaging, Drosophila, NF‐κB, innate immune response, human alpha‐1 antitrypsin, Original Articles, senescence‐associated secretory phenotype
Related Organizations
Funded by
NIH| Rapid Induction of apoptosis against viral infection
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01GM106174-01A1
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
45 references, page 1 of 3

Akbar MA, Cao JJ, Lu Y, Nardo D, Chen MJ, Elshikha AS, Ahamed R, Brantly M, Holliday LS, Song S (2016) Alpha‐1 antitrypsin gene therapy ameliorates bone loss in ovariectomy‐induced osteoporosis mouse model. Hum. Gene Ther. 27, 679–686.27158796 [PubMed]

Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol. 11, R106.20979621 [OpenAIRE] [PubMed]

Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM (2016) Naturally occurring p16(Ink4a)‐positive cells shorten healthy lifespan. Nature 530, 184–189.26840489 [OpenAIRE] [PubMed]

Blice‐Baum AC, Zambon AC, Kaushik G, Viswanathan MC, Engler AJ, Bodmer R, Cammarato A (2017) Modest overexpression of FOXO maintains cardiac proteostasis and ameliorates age‐associated functional decline. Aging Cell 16, 93–103.28090761 [OpenAIRE] [PubMed]

Buchon N, Silverman N, Cherry S (2014) Immunity in Drosophila melanogaster – from microbial recognition to whole‐organism physiology. Nat. Rev. Immunol. 14, 796–810.25421701 [OpenAIRE] [PubMed]

Cao JJ, Gregoire BR, Sun L, Song S (2011) Alpha‐1 antitrypsin reduces ovariectomy‐induced bone loss in mice. Ann. N. Y. Acad. Sci. 1240, E31–E35.22360827 [PubMed]

Churg A, Wang X, Wang RD, Meixner SC, Pryzdial EL, Wright JL (2007) Alpha1‐antitrypsin suppresses TNF‐alpha and MMP‐12 production by cigarette smoke‐stimulated macrophages. Am. J. Respir. Cell Mol. Biol. 37, 144–151.17395890 [PubMed]

Contrepois K, Coudereau C, Benayoun BA, Schuler N, Roux PF, Bischof O, Courbeyrette R, Carvalho C, Thuret JY, Ma Z, Derbois C, Nevers MC, Volland H, Redon CE, Bonner WM, Deleuze JF, Wiel C, Bernard D, Snyder MP, Rube CE, Olaso R, Fenaille F, Mann C (2017) Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression. Nat. Commun. 8, 14995.28489069 [OpenAIRE] [PubMed]

Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J (2008) Senescence‐associated secretory phenotypes reveal cell‐nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853–2868.19053174 [OpenAIRE] [PubMed]

Coppe JP, Desprez PY, Krtolica A, Campisi J (2010) The senescence‐associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118.20078217 [OpenAIRE] [PubMed]

Elshikha AS, Lu Y, Chen MJ, Akbar M, Zeumer L, Ritter A, Elghamry H, Mahdi MA, Morel L, Song S (2016) Alpha 1 antitrypsin inhibits dendritic cell activation and attenuates nephritis in a mouse model of lupus. PLoS ONE 11, e0156583.27232337 [OpenAIRE] [PubMed]

Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr. Rev. 65, S173–S176.18240544 [PubMed]

Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age‐associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69(Suppl 1), S4–S9.24833586 [PubMed]

Freund A, Patil CK, Campisi J (2011) p38MAPK is a novel DNA damage response‐independent regulator of the senescence‐associated secretory phenotype. EMBO J. 30, 1536–1548.21399611 [OpenAIRE] [PubMed]

Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Dechanet‐Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B (2017) Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat. Med. 23, 174–184.28092664 [OpenAIRE] [PubMed]

45 references, page 1 of 3
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