Michael Ristow

Michael Ristow
Michael Ristow
Born April 24, 1967 (1967-04-24) (age 44)
Lübeck, Germany
Nationality German
Fields Biochemistry
Institutions University of Jena, Germany
Harvard University, Cambridge
Joslin Diabetes Center, Boston
University of Cologne, Germany
Alma mater Ruhr University Bochum, Germany
Known for mitohormesis, mitochondrial metabolism

Michael Ristow (b April 24, 1967) is a German medical researcher who has published influential articles on the metabolic basis of human diseases, including type 2 diabetes, obesity and cancer, as well as general aging processes. Amongst more than 50 peer-reviewed scientific publications, Ristow published a seminal article describing a genetic mutation associated with extreme human obesity.[1]

Ristow was born in Lübeck in the North of Germany. He graduated at the University of Bochum in 1992 and received his M.D. from University of Bochum in 1996. He was appointed to the University of Jena in 2005 as a full professor in nutritional science.

Ristow’s laboratory has provided direct evidence supporting the so-called Warburg hypothesis. Specifically Ristow has shown that forced metabolic activity and respiration of mitochondria efficiently blocks cancer growth[2][3] as anticipated by Otto Heinrich Warburg as early as in 1924.

In 2007, Ristow’s group published evidence which could explain the basis of the observed extension of lifespan by restriction of sugar intake. In experiments on a model organism, the worm Caenorhabditis elegans, they found that lowering the availability of glucose extended the lifespan of the worms. It has been known since the 1930s that restricting calories while maintaining adequate amounts of other nutrients extends lifespan across a broad range of organisms. The mechanism has been proposed as a change in the activity of the sirtuins. Interestingly, Michael Ristow shows in his article that this effect can also occur independent of sirtuins, since worms deficient for sirtuins still show extended life span in states of sugar restriction.[4][5][6].

Most importantly, Ristow's research suggests that this is a mitohormetic effect, as reviewed in [7]. Hormesis is a controversial concept in which it has been demonstrated that the induction of a stress can lengthen lifespan in some species. Ristow's interpretation was that in response to a decrease in glycolytic energy production, the worms have to generate ATP by oxidative phosphorylation in the mitochondria, leading to increased production of reactive oxygen species. In response, the organism produces more defenses against oxidative stress, including increased production of catalase. Supplementation with antioxidants abolishes the increase in lifespan, and so does disruption of an AMP-kinase but not disruption of sirtuins.[4]

More recently and experiencing significant media attention[8][9][10], Ristow and colleagues have shown that supplementing humans with antioxidants during exercise blocks the health-promoting effects of exercise, suggesting that free radicals produced during exercise are responsible and required for the effects of exercise [11].

These findings bring into question Denham Harman's free radical theory of aging, and provide a mechanistic basis to question the application of antioxidants to human health.[12][13]

Independent of his work on oxidative stress, Ristow has recently shown that increased concentrations of the trace metal Lithium contained in drinking water are associated with increased lifespan in Japan suggesting a readily available anti-aging intervention[14].

See also

Mitochondrial hormesis

References

  1. ^ Michael Ristow, M.D., Dirk Müller-Wieland, M.D., Andreas Pfeiffer, M.D., Wilhelm Krone, M.D., and C. Ronald Kahn, M.D. (October 1, 1998). "Obesity Associated with a Mutation in a Genetic Regulator of Adipocyte Differentiation". The New England Journal of Medicine 339 (14): 953–959. doi:10.1056/NEJM199810013391403. PMID 9753710. http://content.nejm.org/cgi/content/abstract/339/14/953/. 
  2. ^ Tim J. Schulz, Rene Thierbach, Anja Voigt, Gunnar Drewes, Brun Mietzner, Pablo Steinberg, Andreas F. H. Pfeiffer and Michael Ristow (2006). "Induction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth: Otto Warburg Revisited". J. Biol. Chem. 281 (2): 977–981. doi:10.1074/jbc.M511064200. PMID 16263703. http://www.jbc.org/cgi/reprint/281/2/977.pdf. 
  3. ^ Gergor Beuster, Kim Zarse and Michael Ristow (2011). "Inhibition of alanine aminotransferase in silico and in vivo promotes mitochondrial metabolism to impair malignant growth". J. Biol. Chem. 286 (25): 2232322330. PMID 21540181. http://www.jbc.org/cgi/reprint/286/25/22323. 
  4. ^ a b Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007). "Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress". Cell Metab. 6 (4): 280–93. doi:10.1016/j.cmet.2007.08.011. PMID 17908557. 
  5. ^ "Reuters" article on Ristow’s findings on the positive role of oxidative stress
  6. ^ "Eurekalert" article on Ristow’s findings on the positive role of oxidative stress
  7. ^ Michael Ristow, Sebastian Schmeisser (2011). "Extending lifespan by increasing oxidative stress". Free Radical Biology and Medicine 51 (2): 327–336. PMID 21619928. http://www.sciencedirect.com/science/article/pii/S0891584911003121. 
  8. ^ Antioxidants & exercise: New York Times
  9. ^ Antioxidants & exercise: BBC
  10. ^ Antioxidants & exercise: Scientific American
  11. ^ Michael Ristow, Kim Zarse, ... ,Matthias Blüher (2009). "Antioxidants prevent health-promoting effects of physical exercise in humans". Proc. Natl Acad Sci USA 106 (5): 8865–8870. PMID 19433800. http://www.pnas.org/content/106/21/8665.full.pdf+html. 
  12. ^ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526. 
  13. ^ Ristow, M. .; Zarse, K. . (2010). "How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis)". Experimental gerontology 45 (6): 410–418. doi:10.1016/j.exger.2010.03.014. PMID 20350594.  edit
  14. ^ Kim Zarse, ... , Michael Ristow (2011). "Low-dose lithium uptake promotes longevity in humans and metazoans". Eur J Nutr 50 (5): 387–389. PMID 21301855. http://www.springerlink.com/content/p3jp2013k4p5tq3k/. 

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