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Michael Ristow

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Michael Ristow
Michael Ristow, 2013
Born (1967-04-24) April 24, 1967 (age 57)
Lübeck, Germany
NationalityGerman
Alma materRuhr University Bochum, Germany
Known formitohormesis, antioxidant, mitochondrial metabolism, aging, nutrition
Scientific career
FieldsBiochemistry, Medicine
InstitutionsETH Zurich, Switzerland
University of Jena, Germany
Harvard University, Cambridge
Joslin Diabetes Center, Boston
University of Cologne, Germany

Michael Ristow (b April 24, 1967) is a German medical researcher who has published influential articles on biochemical aspects of mitochondrial metabolism and particularly the possibly health-promoting role of reactive oxygen species in diseases like type 2 diabetes, obesity and cancer, as well as general aging due to a process called mitohormesis.

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, and is a full professor in energy metabolism at the ETH Zurich since 2013.

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. 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.[1][2][3]

Most importantly, Ristow's research suggests that this is a mitohormetic effect, as reviewed in.[4] Hormesis is a controversial concept in which it has been demonstrated that the induction of low-level stress can promote health and lengthen lifespan in some species, while higher levels of the same stress exert detrimental effects. 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. Due to a vaccination-like response, the organism produces more defenses against oxidative stress, including increased activity of catalase. Supplementation with antioxidants abolishes the increase in lifespan, and so does disruption of an AMP-kinase but not disruption of sirtuins.[1]

In a follow-up study that experienced significant media attention,[5][6][7] Ristow and colleagues have shown that supplementing humans with antioxidants during physical exercise blocks the health-promoting effects of exercise, suggesting that free radicals produced during exercise are responsible and required for the effects of exercise.[8]

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.[9][10][11]

Subsequently Ristow demonstrated that the widely used supplement glucosamine promotes longevity of Caenorhabditis elegans and elderly mice.[12] Independently, it was shown that regular intake of glucosamine is associated with a remarkable reduction in mortality in humans, suggesting that glucosamine supplementation may be useful to promote human healthspan.[13]

In earlier years, Ristow published a seminal article describing a genetic mutation associated with extreme human obesity.[14]

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[15][16] as anticipated by Otto Heinrich Warburg as early as in 1924.

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.[17]

See also

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References

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  1. ^ 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 Metabolism. 6 (4): 280–93. doi:10.1016/j.cmet.2007.08.011. PMID 17908557.
  2. ^ "Reuters" article on Ristow’s findings on the positive role of oxidative stress
  3. ^ "Eurekalert" article on Ristow’s findings on the positive role of oxidative stress
  4. ^ Michael Ristow; Sebastian Schmeisser (2011). "Extending lifespan by increasing oxidative stress". Free Radical Biology and Medicine. 51 (2): 327–336. doi:10.1016/j.freeradbiomed.2011.05.010. PMID 21619928.
  5. ^ Antioxidants & exercise: New York Times
  6. ^ Antioxidants & exercise: BBC
  7. ^ Antioxidants & exercise: Scientific American
  8. ^ Michael Ristow, Kim Zarse, ... ,Matthias Blüher (2009). "Antioxidants prevent health-promoting effects of physical exercise in humans". Proc. Natl. Acad. Sci. U.S.A. 106 (5): 8865–8870. Bibcode:2009PNAS..106.8665R. doi:10.1073/pnas.0903485106. PMC 2680430. PMID 19433800.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ 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.
  10. ^ Ristow M (2014). "Unraveling the truth about antioxidants: mitohormesis explains ROS-induced health benefits". Nature Medicine. 20 (7): 709–11. doi:10.1038/nm.3624. PMID 24999941. S2CID 32448892.
  11. ^ 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. S2CID 207727334.
  12. ^ Weimer S; et al. (2013). "D-Glucosamine supplementation extends life span of nematodes and of ageing mice". Nature Communications. 8: 3563. doi:10.1038/ncomms4563. PMC 3988823. PMID 24714520.
  13. ^ Bell G. A.; et al. (2012). "Use of glucosamine and chondroitin in relation to mortality". European Journal of Epidemiology. 27 (8): 593–603. doi:10.1007/s10654-012-9714-6. PMC 3557824. PMID 22828954.
  14. ^ Ristow, Michael; Müller-Wieland, Dirk; Pfeiffer, Andreas; Krone, Wilhelm; Kahn, C. Ronald (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.
  15. ^ Tim J. Schulz; Rene Thierbach; Anja Voigt; Gunnar Drewes; Brun Mietzner; Pablo Steinberg; Andreas F. H. Pfeiffer; Michael Ristow (2006). "Induction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth: Otto Warburg Revisited" (PDF). The Journal of Biological Chemistry. 281 (2): 977–981. doi:10.1074/jbc.M511064200. PMID 16263703. S2CID 31545439.
  16. ^ Gergor Beuster, Kim Zarse & Michael Ristow (2011). "Inhibition of alanine aminotransferase in silico and in vivo promotes mitochondrial metabolism to impair malignant growth". Journal of Biological Chemistry. 286 (25): 22323–30. doi:10.1074/jbc.M110.205229. PMC 3121379. PMID 21540181.
  17. ^ Kim Zarse, ... , Michael Ristow (2011). "Low-dose lithium uptake promotes longevity in humans and metazoans". Eur J Nutr. 50 (5): 387–389. doi:10.1007/s00394-011-0171-x. PMC 3151375. PMID 21301855.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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