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Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

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Abstract
The antiglycemic drug metformin, widely prescribed as first-line treatment of type II diabetes mellitus, has lifespan-extending properties. Precisely how this is achieved remains unclear. Via a quantitative proteomics approach using the model organism Caenorhabditis elegans, we gained molecular understanding of the physiological changes elicited by metformin exposure, including changes in branched-chain amino acid catabolism and cuticle maintenance. We show that metformin extends lifespan through the process of mitohormesis and propose a signaling cascade in which metformin-induced production of reactive oxygen species increases overall life expectancy. We further address an important issue in aging research, wherein so far, the key molecular link that translates the reactive oxygen species signal into a prolongevity cue remained elusive. We show that this beneficial signal of the mitohormetic pathway is propagated by the peroxiredoxin PRDX-2. Because of its evolutionary conservation, peroxiredoxin signaling might underlie a general principle of prolongevity signaling.
Keywords
COMPLEX I, CHAIN AMINO-ACIDS, MICE, C. ELEGANS, RESPIRATORY-CHAIN, OXIDATIVE STRESS-RESPONSE, ACTIVATED PROTEIN-KINASE, DIETARY RESTRICTION, RESTRICTION-INDUCED LONGEVITY, AGING CAENORHABDITIS-ELEGANS

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MLA
De Haes, Wouter, Lotte Frooninckx, Roel Van Assche, et al. “Metformin Promotes Lifespan Through Mitohormesis via the Peroxiredoxin PRDX-2.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.24 (2014): E2501–E2509. Print.
APA
De Haes, Wouter, Frooninckx, L., Van Assche, R., Smolders, A., Depuydt, G., Billen, J., Braeckman, B., et al. (2014). Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(24), E2501–E2509.
Chicago author-date
De Haes, Wouter, Lotte Frooninckx, Roel Van Assche, Arne Smolders, Geert Depuydt, Johan Billen, Bart Braeckman, Liliane Schoofs, and Liesbet Temmerman. 2014. “Metformin Promotes Lifespan Through Mitohormesis via the Peroxiredoxin PRDX-2.” Proceedings of the National Academy of Sciences of the United States of America 111 (24): E2501–E2509.
Chicago author-date (all authors)
De Haes, Wouter, Lotte Frooninckx, Roel Van Assche, Arne Smolders, Geert Depuydt, Johan Billen, Bart Braeckman, Liliane Schoofs, and Liesbet Temmerman. 2014. “Metformin Promotes Lifespan Through Mitohormesis via the Peroxiredoxin PRDX-2.” Proceedings of the National Academy of Sciences of the United States of America 111 (24): E2501–E2509.
Vancouver
1.
De Haes W, Frooninckx L, Van Assche R, Smolders A, Depuydt G, Billen J, et al. Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2014;111(24):E2501–E2509.
IEEE
[1]
W. De Haes et al., “Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 111, no. 24, pp. E2501–E2509, 2014.
@article{5778343,
  abstract     = {The antiglycemic drug metformin, widely prescribed as first-line treatment of type II diabetes mellitus, has lifespan-extending properties. Precisely how this is achieved remains unclear. Via a quantitative proteomics approach using the model organism Caenorhabditis elegans, we gained molecular understanding of the physiological changes elicited by metformin exposure, including changes in branched-chain amino acid catabolism and cuticle maintenance. We show that metformin extends lifespan through the process of mitohormesis and propose a signaling cascade in which metformin-induced production of reactive oxygen species increases overall life expectancy. We further address an important issue in aging research, wherein so far, the key molecular link that translates the reactive oxygen species signal into a prolongevity cue remained elusive. We show that this beneficial signal of the mitohormetic pathway is propagated by the peroxiredoxin PRDX-2. Because of its evolutionary conservation, peroxiredoxin signaling might underlie a general principle of prolongevity signaling.},
  author       = {De Haes, Wouter and Frooninckx, Lotte and Van Assche, Roel and Smolders, Arne and Depuydt, Geert and Billen, Johan and Braeckman, Bart and Schoofs, Liliane and Temmerman, Liesbet},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {COMPLEX I,CHAIN AMINO-ACIDS,MICE,C. ELEGANS,RESPIRATORY-CHAIN,OXIDATIVE STRESS-RESPONSE,ACTIVATED PROTEIN-KINASE,DIETARY RESTRICTION,RESTRICTION-INDUCED LONGEVITY,AGING CAENORHABDITIS-ELEGANS},
  language     = {eng},
  number       = {24},
  pages        = {E2501--E2509},
  title        = {Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2},
  url          = {http://dx.doi.org/10.1073/pnas.1321776111},
  volume       = {111},
  year         = {2014},
}

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