Advanced glycation end products in our diet may suppress sirtuin enzyme activity and play a role in age-related brain volume loss.
Reducing Glycotoxin Intake to Prevent Alzheimer’s
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Each of us has six billion miles of DNA. How does our body keep it from getting all tangled up? There are special proteins called histones, which act like spools, with DNA as the thread. Enzymes called sirtuins wrap the DNA around the histone spools, and by doing so, silence whatever genes were in that stretch of DNA–hence their name SIRtuins, which stands for silencing information regulator.
Although they were discovered only about a decade ago, the study of sirtuins has become one of the most promising areas of biomedicine, since they appear to be involved in promoting healthy aging and longevity. Suppression of this key host defense is considered a central feature of Alzheimer’s disease.
Autopsies of Alzheimer’s victims reveal that loss of sirtuin enzyme activity is closely associated with the accumulation of the plaques and tangles in the brain that are characteristic of Alzheimer’s disease. Sirtuins appear to activate pathways that steer the brain away from the formation of plaque and entangled proteins. Because a decrease in sirtuin activity can clearly have deleterious effects on nerve health, they’re trying to come up with drugs to increase sirtuin activity–but why not just prevent its suppression in the first place?
Glycotoxins in our food suppress sirtuin activity, these so-called advanced glycation end products, or AGEs. Our modern diet includes excessive AGE’s, which can be neurotoxic. High levels in the blood may predict cognitive decline over time.
If you measure the urine levels of glycotoxins flowing through the bodies of older adults, those with the highest levels went on to suffer the greatest cognitive decline over the subsequent nine years.
As we age, our brain literally shrinks. In our 60s and 70s we lose an average of five cubic centimeters of total brain tissue volume every year, but some lose more than others. Brain atrophy may be reduced in very healthy individuals. And a few people don’t lose any brain at all. Normally, we lose about 2% of brain volume every year, but that’s just the average. Although the average brain loss for folks in their 70s and 80s was 2.1%, some lost more, some lost less, and some men and women lost none at all over a period of four years.
Researchers in Australia provided the first evidence linking AGEs with this kind of cerebral brain loss. So limiting one’s consumption of these compounds may end up having significant public health benefits.
Because sirtuin deficiency is both preventable and reversible by dietary AGE reduction, a therapeutic strategy that includes eating less AGEs may offer a new strategy to combat the epidemic of Alzheimer’s.
Some of these glycotoxins are produced internally, particularly in diabetics, but anyone can get them from smoking and eating–particularly foods high in fat and protein.
In a previous video I listed the 15 foods most contaminated with glycotoxins–mostly chicken, but also pork, beef, and fish–which may help explain why those who eat the most meat may have triple the risk of getting dementia, compared to long-time vegetarians.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- M S Beeri, E Moshier, J Schmeidler, J Godbold, J Uribarri, S Reddy, M Sano, H T Grossman, W Cai, H Vlassara, J M Silverman. Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Mech Ageing Dev. 2011 Nov-Dec;132(11-12):583-7.
- F Zhang, S Wang, L Gan, P S Vosler, Y Gao, M J Zigmond, J Chen. Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol. 2011 Nov;95(3):373-95.
- N Braidy, T Jayasena, A Poljak, P S Sachdev. Sirtuins in cognitive ageing and Alzheimer's disease. Curr Opin Psychiatry. 2012 May;25(3):226-30.
- S M Resnick, D L Pham, M A Kraut, A B Zonderman, C Davatzikos. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003 Apr 15;23(8):3295-301.
- S Park, R Mori, I Shimokawa. Do sirtuins promote mammalian longevity? A critical review on its relevance to the longevity effect induced by calorie restriction. Mol Cells. 2013 Jun;35(6):474-80.
- V Srikanth, B Westcott, J Forbes, T G Phan, R Beare, A Venn, S Pearson, T Greenaway, V Parameswaran, G Munch. Methylglyoxal, cognitive function and cerebral atrophy in older people. J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):68-73.
- C Julien, C Tremblay, V Emond, M Lebbadi, N Salem Jr, F Calon. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J Neuropathol Exp Neurol. 2009 Jan;68(1):48-58.
- R Mostoslavsky, M Esteller, A Vaquero. At the crossroad of lifespan, calorie restriction, chromatin and disease: meeting on sirtuins. Cell Cycle. 2010 May 15;9(10):1907-12.
- L Guarente. Franklin H. Epstein Lecture: Sirtuins, aging, and medicine. N Engl J Med. 2011 Jun 9;364(23):2235-44.
- C Leuvano-Contreras, K Chapman-Novakofski. Dietary advanced glycation end products and aging. Nutrients. 2010 Dec;2(12):1247-65.
- K Yaffe, K Lindquist, A V Schwartz, C Vitartas, E Vittinghoff, S Satterfield, E M Simonsick, L LAuner, C Rosano, J A Cauley, T Harris. Advanced glycation end product level, diabetes, and accelerated cognitive aging. Neurology. 2011 Oct 4;77(14):1351-6.
- W Cai, J Uribarri, L Zhu, X Chen, S Swamy, et al. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4940-5.
- Y Tang, GT Whitman, I Lopez, RW Baloh. Brain volume changes on longitudinal magnetic resonance imaging in normal older people. J Neuroimaging. 2001 Oct;11(4):393-400.
- P Giem, WL Beeson, GE Fraser. The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology. 1993;12(1):28-36.
Images thanks to Meagan via Flickr and Richard Wheeler via Wikimedia Commons.
Each of us has six billion miles of DNA. How does our body keep it from getting all tangled up? There are special proteins called histones, which act like spools, with DNA as the thread. Enzymes called sirtuins wrap the DNA around the histone spools, and by doing so, silence whatever genes were in that stretch of DNA–hence their name SIRtuins, which stands for silencing information regulator.
Although they were discovered only about a decade ago, the study of sirtuins has become one of the most promising areas of biomedicine, since they appear to be involved in promoting healthy aging and longevity. Suppression of this key host defense is considered a central feature of Alzheimer’s disease.
Autopsies of Alzheimer’s victims reveal that loss of sirtuin enzyme activity is closely associated with the accumulation of the plaques and tangles in the brain that are characteristic of Alzheimer’s disease. Sirtuins appear to activate pathways that steer the brain away from the formation of plaque and entangled proteins. Because a decrease in sirtuin activity can clearly have deleterious effects on nerve health, they’re trying to come up with drugs to increase sirtuin activity–but why not just prevent its suppression in the first place?
Glycotoxins in our food suppress sirtuin activity, these so-called advanced glycation end products, or AGEs. Our modern diet includes excessive AGE’s, which can be neurotoxic. High levels in the blood may predict cognitive decline over time.
If you measure the urine levels of glycotoxins flowing through the bodies of older adults, those with the highest levels went on to suffer the greatest cognitive decline over the subsequent nine years.
As we age, our brain literally shrinks. In our 60s and 70s we lose an average of five cubic centimeters of total brain tissue volume every year, but some lose more than others. Brain atrophy may be reduced in very healthy individuals. And a few people don’t lose any brain at all. Normally, we lose about 2% of brain volume every year, but that’s just the average. Although the average brain loss for folks in their 70s and 80s was 2.1%, some lost more, some lost less, and some men and women lost none at all over a period of four years.
Researchers in Australia provided the first evidence linking AGEs with this kind of cerebral brain loss. So limiting one’s consumption of these compounds may end up having significant public health benefits.
Because sirtuin deficiency is both preventable and reversible by dietary AGE reduction, a therapeutic strategy that includes eating less AGEs may offer a new strategy to combat the epidemic of Alzheimer’s.
Some of these glycotoxins are produced internally, particularly in diabetics, but anyone can get them from smoking and eating–particularly foods high in fat and protein.
In a previous video I listed the 15 foods most contaminated with glycotoxins–mostly chicken, but also pork, beef, and fish–which may help explain why those who eat the most meat may have triple the risk of getting dementia, compared to long-time vegetarians.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- M S Beeri, E Moshier, J Schmeidler, J Godbold, J Uribarri, S Reddy, M Sano, H T Grossman, W Cai, H Vlassara, J M Silverman. Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Mech Ageing Dev. 2011 Nov-Dec;132(11-12):583-7.
- F Zhang, S Wang, L Gan, P S Vosler, Y Gao, M J Zigmond, J Chen. Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol. 2011 Nov;95(3):373-95.
- N Braidy, T Jayasena, A Poljak, P S Sachdev. Sirtuins in cognitive ageing and Alzheimer's disease. Curr Opin Psychiatry. 2012 May;25(3):226-30.
- S M Resnick, D L Pham, M A Kraut, A B Zonderman, C Davatzikos. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003 Apr 15;23(8):3295-301.
- S Park, R Mori, I Shimokawa. Do sirtuins promote mammalian longevity? A critical review on its relevance to the longevity effect induced by calorie restriction. Mol Cells. 2013 Jun;35(6):474-80.
- V Srikanth, B Westcott, J Forbes, T G Phan, R Beare, A Venn, S Pearson, T Greenaway, V Parameswaran, G Munch. Methylglyoxal, cognitive function and cerebral atrophy in older people. J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):68-73.
- C Julien, C Tremblay, V Emond, M Lebbadi, N Salem Jr, F Calon. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J Neuropathol Exp Neurol. 2009 Jan;68(1):48-58.
- R Mostoslavsky, M Esteller, A Vaquero. At the crossroad of lifespan, calorie restriction, chromatin and disease: meeting on sirtuins. Cell Cycle. 2010 May 15;9(10):1907-12.
- L Guarente. Franklin H. Epstein Lecture: Sirtuins, aging, and medicine. N Engl J Med. 2011 Jun 9;364(23):2235-44.
- C Leuvano-Contreras, K Chapman-Novakofski. Dietary advanced glycation end products and aging. Nutrients. 2010 Dec;2(12):1247-65.
- K Yaffe, K Lindquist, A V Schwartz, C Vitartas, E Vittinghoff, S Satterfield, E M Simonsick, L LAuner, C Rosano, J A Cauley, T Harris. Advanced glycation end product level, diabetes, and accelerated cognitive aging. Neurology. 2011 Oct 4;77(14):1351-6.
- W Cai, J Uribarri, L Zhu, X Chen, S Swamy, et al. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4940-5.
- Y Tang, GT Whitman, I Lopez, RW Baloh. Brain volume changes on longitudinal magnetic resonance imaging in normal older people. J Neuroimaging. 2001 Oct;11(4):393-400.
- P Giem, WL Beeson, GE Fraser. The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology. 1993;12(1):28-36.
Images thanks to Meagan via Flickr and Richard Wheeler via Wikimedia Commons.
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Title
Reducing Glycotoxin Intake to Prevent Alzheimer’s
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
I’m so glad I was able to finally cover sirtuins. Such important enzymes, but I was waiting for a dietary tie-in.
I’ve covered advanced glycation end-products previously in:
More on slowing brain aging in How to Slow Brain Aging By Two Years.
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