Cited by 200Advanced Glycation End Products researchRetinal Diseases and TreatmentsGenetics, Aging, and Longevity in Model Organisms

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Glycation‐altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age‐related disease (in nondiabetics)

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Uchiki, Tomoaki, Weikel, Karen A., Jiao, Wangwang, Shang, Fu, Caceres, Andrea, Pawlak, Dorota, Handa, James T., Brownlee, Michael, Nagaraj, Ram, Taylor, Allen·2012·Aging Cell

DOI 10.1111/j.1474-9726.2011.00752.xPMC PMC3257376

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Abstract

Summary: Epidemiologic studies indicate that the risks for major age‐related debilities including coronary heart disease, diabetes, and age‐related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains the salutary effect is a barrier to implementing dietary practices that capture the benefits of consuming lower GI diets. We established a simple murine model of age‐related retinal lesions that precede AMD (hereafter called AMD‐like lesions). We found that consuming a higher GI diet promotes these AMD‐like lesions. However, mice that consumed the lower vs. higher GI diet had significantly reduced frequency (P < 0.02) and severity (P < 0.05) of hallmark age‐related retinal lesions such as basal deposits. Consuming higher GI diets was associated with > 3 fold higher accumulation of advanced glycation end products (AGEs) in retina, lens, liver, and brain in the age‐matched mice, suggesting that higher GI diets induce systemic glycative stress that is etiologic for lesions. Data from live cell and cell‐free systems show that the ubiquitin–proteasome system (UPS) and lysosome/autophagy pathway [lysosomal proteolytic system (LPS)] are involved in the degradation of AGEs. Glycatively modified substrates were degraded significantly slower than unmodified substrates by the UPS. Compounding the detriments of glycative stress, AGE modification of ubiquitin and ubiquitin‐conjugating enzymes impaired UPS activities. Furthermore, ubiquitin conjugates and AGEs accumulate and are found in lysosomes when cells are glycatively stressed or the UPS or LPS/autophagy are inhibited, indicating that the UPS and LPS interact with one another to degrade AGEs. Together, these data explain why AGEs accumulate as glycative stress increases.

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Written from the paper’s full text.

TL;DR

In a murine model, consuming a lower glycemic index diet delayed AMD-like retinal lesions and reduced tissue accumulation of advanced glycation end products (AGEs), while a higher GI diet increased glycative stress. Glycation impairs protein degradation by making substrates resistant and damaging ubiquitination machinery, with the ubiquitin-proteasome system and autophagic-lysosomal pathway cooperating to clear AGEs.

Key findings

In 23.5-month-old mice fed low vs. high GI diets for 7 months, lower GI was associated with less deposition of basal laminar deposits (p=0.02) and smaller basal laminar deposits (p=0.05); the abstract reports reduced frequency (p<0.02) and severity (p<0.05) of hallmark age-related retinal lesions.
Higher GI diets were associated with ~3-, 7-, 8-, and 34-fold higher levels of MG-H1 in retina, liver, lens, and brain, respectively, in age-matched mice; human lens showed 8-fold higher MG-H1 in a 76- vs. 22-year-old, and mouse brain showed 1.5-fold higher AGEs at 22 vs. 3 months.
MGO exposure reduced intracellular protein degradation by 60% at 1.7 mM and >80% at 2.5 mM; glycated ubiquitin decreased degradation of αA162 by ~27% (G6P-modified) and ~40% (MGO-modified), whereas wild-type ubiquitin increased degradation by ≥20% and unmodified Ubc4 increased degradation by 80%.
UPS and LPS/autophagy inhibitors delayed AGE clearance: at 14 h after 1 mM MGO, inhibitors retained ~2-fold higher MG-H1; 3MA increased AGE levels by >70%; blocking both UPS and LPS doubled the AGE/ubiquitin-conjugate ratio in the ubiquitin-conjugate pool.

Methods

C57BL/6 mice (and some 129SvPas mice) were fed low- vs. high-GI diets; retinal lesions were assessed by electron microscopy (>84 fields in four low-GI and three high-GI 23.5-month-old mice after 7 months), alongside glucose tolerance, AGE/MG-H1 measurements, carbonyls, and immunohistochemistry in retina, lens, liver, and brain.
Cultured RPE cells and cell-free lysates were exposed to glucose or MGO; analyses included intracellular proteolysis assays, UPS reporter Ub-G76V-GFP, ubiquitination/degradation assays with wild-type or glycated ubiquitin and Ubc4, proteasome activity, lysosomal fractionation, colocalization, and pulldown of ubiquitin conjugates, with inhibitors of the UPS, LPS, and autophagy (3MA).
Experimental procedures are stated to be in Supporting Information.

Limitations

Stated: small sample size meant some retinal differences (basal infoldings, cytoplasmic vacuoles) were not statistically significant; the possibility that some lysosomal AGEs are formed in situ could not be eliminated.
Evident: mechanistic conclusions rely heavily on cultured RPE and cell-free systems, so the causal link in humans is not directly tested; high-GI mice had higher HOMA-IR than low-GI mice, although fasting insulin and glucose were within normal ranges, indicating diet effects were separable from diabetes but not metabolically identical.

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Integrity signals

Registry

Crossref · 10.1111/j.1474-9726.2011.00752.x

Cites

106 of 106 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

50 Own result · 39 Own interpretation · 29 Not checked yet · 6 No basis given · 3 Own method

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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We established a simple murine model of age-related retinal lesions that precede AMD (hereafter called AMD-like lesions).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consuming higher GI diets was associated with >3 fold higher accumulation of advanced glycation end products (AGEs) in retina, lens, liver and brain in the age-matched mice”
- Also stated in: § Consuming lower GI diets delays AMD-like lesions · plain
  “We observed ∼3, 7, 8 and 34 fold higher levels of MG-H1 in retina, liver, lens and brain (primarily substantia nigra) from mice of the same age that consumed the higher –as opposed to the lower –GI diet (Figure 2 A-D).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, mice that consumed the lower vs. higher GI diet had significantly reduced frequency (p<0.02) and severity (p<0.05) of hallmark age-related retinal lesions such as basal deposits.”
- Also stated in: § Consuming lower GI diets delays AMD-like lesions · plain
  “Notably, eating the lower GI diet was associated with less deposition of basal laminar deposits (p=0.02) and smaller basal laminar deposits (p=0.05; Figure 1B, Figure S1A, B).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
plain
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Data from live cell and cell free systems show that the ubiquitin-proteasome system (UPS) and lysosome/autophagy pathway (LPS) are involved in the degradation of AGEs.”
- Also stated in: § A UPS and an autophagic-LPS collaborate to remove AGEs · hedged
  “Taken together, these data provide the first indication that a UPS and LPS both play roles in the removal of AGEs and they indicate a dynamic flux of AGEs and ubiquitinated species between these compartments.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Glycatively-modified substrates were degraded significantly slower than unmodified substrates by the UPS.”
- Also stated in: § Glycation induced reduction in UPS proteolytic activity · plain
  “Consistent with findings that total proteolysis is depressed upon glycative stress, glycation of these substrates decreased their susceptibility to degradation (Figure 3D-H)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
plain
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, mice that consumed the lower vs. higher GI diet had significantly reduced frequency (p<0.02) and severity (p<0.05) of hallmark age-related retinal lesions such as basal deposits.”
- Also stated in: § Consuming lower GI diets delays AMD-like lesions · plain
  “Notably, eating the lower GI diet was associated with less deposition of basal laminar deposits (p=0.02) and smaller basal laminar deposits (p=0.05; Figure 1B, Figure S1A, B).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
plain
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compounding the detriments of glycative stress, AGE-modification of ubiquitin and ubiquitin conjugating enzymes impaired UPS activities.”
- Also stated in: § Glycation induced reduction in UPS proteolytic activity · hedged
  “Taken together, these data indicate that the degradation of AGE-modified proteins requires UPS capacities, and that glycation impairs the ability of ubiquitin and ubiquitin conjugating enzymes to catalyze ubiquitination.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
plain
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, eating the lower GI diet was associated with less deposition of basal laminar deposits (p=0.02) and smaller basal laminar deposits (p=0.05; Figure 1B, Figure S1A, B).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Surprisingly, glycation is without effect on proteasomal activity (Figure 5E).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and 1.5 fold higher levels of AGEs in 22 month old vs. 3 month old mouse brains from animals that consumed the same diet (Figure S1D, E).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“albeit that HOMA-IR levels were higher for the high-GI fed mice than the low-GI fed mice (Weikel, manuscript in preparation)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with findings that total proteolysis is depressed upon glycative stress, glycation of these substrates decreased their susceptibility to degradation (Figure 3D-H)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
plain
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The AGEs were subsequently cleared after removal of MGO (Figure 3B).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, immunohistochemical analysis shows that AGEs are distributed throughout the retina and specifically in areas where AMD-related lesions are found- i.e. the RPE, Bruch's membrane and the choroid (Figure 2F vs. E, purple, Figure 1B)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
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correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the ability of Ubc4 to support ubiquitin conjugate formation was inversely related to the extent of glycation (Figure 5C lanes 2-5).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, addition of equivalent levels of glycated ubiquitin resulted in far lower levels of conjugates (Figure 5A lanes 3, 4 vs. 2).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Exposure to only 1.7 or 2.5 mM MGO reduced the rate of intracellular protein degradation by 60% and >80%, respectively (Figure 3C, left and right panels), coincident with the observed accumulation of AGEs in RPE cells (Figure 3A).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A major role for the UPS in the degradation of both unmodified and MGO-modified αA162 and glutathiolated γ-C crystallin was confirmed since the degradation was dependent upon ATP (Figure 3D), a hallmark for the UPS”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
boosted
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The data in Figure 1A establish that feeding C57BL/6 mice a lower GI diet results in smaller changes in blood glucose levels (upper panel), represented as area under the blood glucose curve (AUC) (lower panel), following intake of glucose.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AGEs accumulate rapidly at rates that are proportionate to the extent of glycative stress (Figure 3A, also see next section).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, vastly higher levels of protein carbonyls (Figure S2), a marker of oxidative stress, were observed in retinas of these and other C57BL6 mice fed the higher GI diet.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Corroborating that glycative stress impairs the catalytic competence of the UPS, we observed that brief pretreatment of reticulocyte or RPE lysates with MGO significantly impeded the degradation of exogenous unmodified αA162, a model substrate of the UPS (Figure S5A,B).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
plain
direct
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, eating the lower GI diet was associated with less deposition of basal laminar deposits (p=0.02) and smaller basal laminar deposits (p=0.05; Figure 1B, Figure S1A, B).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with prior data from various tissues, we observed an 8-fold higher level of MG-H1 in a 76 year old vs. a 22 year old human lens”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Prior to clearance, the AGEs were initially in detergent soluble and insoluble fractions (Figure S9C i.e. lanes 6, 11).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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None of the sources cited for this claim have been checked yet.
In the paper
“Levels of AGEs appear to be elevated in the basal areas of affected RPE (Figure 2)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Farboud et al., 1999
- Not checked yetcites Crabb et al., 2002
hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Glycative stress was also related to accumulation of ubiquitin conjugates.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also observed glycative stress-induced perturbation of LPS activity (Figure 6).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“When they are chased to the lysosome, they appear to collect at the membranes rather than being effectively internalized where they might be more readily degraded.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The ability of the UPS and LPS in cultured RPE cells to clear AGEs, even after exposure to relatively high concentrations of MGO, is in keeping with the biological resiliency and function of these cells.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we established the first mammalian model in which consuming a lower GI diet is associated with delayed appearance of AMD-like lesions.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, we observed higher levels of intracellular AGEs in diverse tissues from animals of the same age that consumed the higher GI diet.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our finding increased levels of ubiquitin conjugates in many age-related debilities, when cells confront chronic stress (Taylor et al., 2002), and in glycatively stressed RPE”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
correlational
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On average, the lysosomal AGEs are comprised of proteins with higher masses.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, they were cleared first from the soluble fraction and only subsequently from the insoluble fraction (Figure S9C i.e. lanes 9, 14).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Further, inhibition of proteolytic potential by blocking the UPS and LPS resulted in a doubling of the ratio of AGEs/ubiquitin conjugates in the ubiquitin conjugate pool in MGO exposed cells (lanes 8 vs. 6).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“It is noteworthy that the more AGEs and ubiquitin conjugates accumulate, the greater the proportion of these moieties that is directed to the insoluble fraction.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observation of >70% higher levels of the most AGEs when MGO treated cells were exposed to 3MA suggests that autophagic-lysosomal proteolysis is involved in degradation of AGEs (Figure 6A, lane 10 vs. 7 or 14 vs. 11, Figure S6A, lane 6 vs. 3).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As noted in Figure S8B (right panel), within the lysosomal fraction the highest proportion and the vast majority of the AGEs, including the highest mass moieties, were in the membrane fraction with only low levels being found in the lumen.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The phenomenon is systemic, affecting the proteome in tissues with the highest levels of oxygenation, rapid metabolism and protein turnover (retina and brain) as well as the lowest oxygen tension, slowest metabolism and rates of overall protein turnover (lens).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In cells that were exposed briefly to 1mM MGO AGEs accumulated rapidly (Figure 3B, Figure 6A lane 2 vs. 1).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this work, we describe a previously undocumented positive relationship between dietary GI and glycative stress-associated lesions”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, at 14hrs after the MGO exposure, cells that had been treated with 1mM MGO and UPS or LPS inhibitor retained ∼2-fold higher levels of MG-H1”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The greater levels of AGEs (especially of higher mass) in cells exposed to both UPS and LPS inhibitors compared to cells exposed to only UPS or LPS inhibitors (Figure 6C, top panel, compare lanes 5 vs. 2-4) is consistent with a synergistic role for the LPS and UPS in removal of AGEs.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
hedged
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting diet-induced systemic glycative stress that is etiologic for lesions.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
hedged
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that consuming a higher GI diet promotes these AMD-like lesions.”
- Also stated in: § Consuming lower GI diets delays AMD-like lesions · boosted
  “Since the only difference between the groups was the GI of their food, it is clear that consuming lower GI diets is associated with delayed risk for AMD-like lesions in these mice.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
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None of the sources cited for this claim have been checked yet.
In the paper
“Recent reports document accumulation of advanced glycation end products (AGEs) in drusen, clinical markers of early AMD that develop posterior to the retinal pigment epithelial cells (RPE) (Ishibashi et al., 1998; Farboud et al., 1999; Crabb et al., 2002).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Ishibashi et al., 1998
- Not checked yetcites Farboud et al., 1999
- Not checked yetcites Crabb et al., 2002
plain
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that the UPS and LPS interact with one another to degrade AGEs.”
- Also stated in: § A UPS and an autophagic-LPS collaborate to remove AGEs · hedged
  “These apparent functional relationships between the UPS and LPS when cells are under glycative stress are also indicated by finding higher levels of ubiquitin conjugates when cells were treated with higher levels of lysosomal inhibitor (Figure S9A, compare lanes 10-12 vs. 4-6).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
hedged
direct
None of the sources cited for this claim have been checked yet.
In the paper
“Epidemiologic studies indicate that the risks for major age-related debilities including CHD, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets”
- Also stated in: § Introduction · boosted
  “Importantly, it has recently been demonstrated that consuming lower glycemic index (GI) diets is associated with diminished risk for onset or progress of AMD, major age-related life threatening and life-quality limiting debilities including coronary heart disease (CHD), type 2 diabetes, and possibly age-related cataract even in non diabetic subjects”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
What the sources say
- Not checked yetcites Salmeron et al., 1997
- Not checked yetcites Augustin et al., 2002
- Not checked yetcites Chiu et al., 2007a
boosted
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together these data explain why AGEs accumulate as glycative stress increases.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
plain
direct
None of the sources cited for this claim have been checked yet.
In the paper
“AGEs have also been etiologically related to disease (Chylack et al., 1994; Chylack, 1999; Tian et al., 2005; Tezel et al., 2007; Glenn & Stitt, 2009).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
What the sources say
- Not checked yetcites Chylack et al., 1994
- Not checked yetcites Chylack, 1999
- Not checked yetcites Tian et al., 2005
plain
direct
In the paper
“The lesions we observed are similar to alterations that precede AMD in humans (Rattner & Nathans, 2006).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Rattner & Nathans, 2006
plain
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data support the idea that the age-related accumulation of AGEs is due, at least in part, to their resistance to degradation.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
hedged
conditional
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that glycation impairs the ability of ubiquitin and ubiquitin conjugating enzymes to catalyze ubiquitination.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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In the paper
“RPE have the highest proteolytic burden in the body as they engulf and must digest the outer 10% of photoreceptors that are shed every night.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Snodderly et al., 2002
plain
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since the only difference between the groups was the GI of their food, it is clear that consuming lower GI diets is associated with delayed risk for AMD-like lesions in these mice.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
boosted
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data confirm that exposure to glycative stress results in limited proteolytic potential, consistent with accumulation of AGEs and carbonyls in tissues derived from the high vs. low dGI mice.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
boosted
direct
In the paper
“Thus, using a high GI diet we can replicate in the mouse retina, and specifically in RPE, the accumulation of AGEs and other markers of oxidative stress that occurs in the human retina upon aging and AMD (Crabb et al., 2002).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
What the sources say
- Not checked yetcites Crabb et al., 2002
plain
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, there appears to be a vicious cycle of diet and metabolism-induced glycative stress, accumulation of AGEs, and attenuated cell and tissue protein homeostasis and dynamics.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
hedged
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Their accumulation after brief exposures to higher levels of MGO suggests that the protein degradation machinery, which is involved in removing such AGEs, cannot keep pace with rates of AGE formation.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
hedged
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data indicate that substrates that are ubiquitinated with glycated ubiquitin act as inhibitors of UPS dependent degradation similar to the conjugation competent but proteolytically incompetent K6W-Ub variant (Figure 5B, lane 3)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
hedged
direct
None of the sources cited for this claim have been checked yet.
In the paper
“These findings show that we can replicate in mice the dietary-carbohydrate blood-glucose relationships that had been established in humans and other mouse models (Jenkins et al., 2002; Scribner et al., 2008; van Schothorst et al., 2008; Isken et al., 2009).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
What the sources say
- Not checked yetcites Jenkins et al., 2002
- Not checked yetcites Scribner et al., 2008
- Not checked yetcites van Schothorst et al., 2008
plain
correlational
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The data indicate that glycative stress of RPE in culture is an appropriate model for determining mechanisms by which glycative stress promotes accumulation of AGEs and other pathobiochemical and pathophysiologic events in the aging retina.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these data indicate that the degradation of AGE-modified proteins requires UPS capacities”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
hedged
direct
In the paper
“MGO is a primary glycating metabolite of glucose (Brownlee, 2001).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Brownlee, 2001
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direct
None of the sources cited for this claim have been checked yet.
In the paper
“because conditions which favor formation of such AGEs were previously associated with cytotoxicity, disease, oxidative stress, senescence and aging, and diminished cell viability (Tessier et al., 1999; Ihnat et al., 2007; Goligorsky et al., 2009; Guix et al., 2009; Vlassara et al., 2009; Wei et al., 2009; Ahmed et al., 2010).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Tessier et al., 1999
- Not checked yetcites Ihnat et al., 2007
- Not checked yetcites Goligorsky et al., 2009
plain
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This indicates that the modified ubiquitins are less effectively incorporated into the high-mass ubiquitin conjugates that are usual substrates for degradation.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
hedged
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The reduced susceptibility to degradation of AGEs appears to be generalizable since it is observed with different substrates and various proteolytic systems (Figure 3D-H, Figure S4 F, G).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
hedged
correlational
None of the sources cited for this claim have been checked yet.
In the paper
“It was also shown that drusen in AMD patients contain ubiquitin conjugates (Ishibashi et al., 1998; Crabb et al., 2002)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Ishibashi et al., 1998
- Not checked yetcites Crabb et al., 2002
plain
None of the sources cited for this claim have been checked yet.
In the paper
“Age-related modification of proteins by sugars or potent glycating sugar metabolites such as MGO, results in formation of AGEs such as hydroimidazolone adducts (MG-H1) (Brownlee, 2001; Thornalley et al., 2003; Pawlak et al., 2004).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
What the sources say
- Not checked yetcites Brownlee, 2001
- Not checked yetcites Thornalley et al., 2003
- Not checked yetcites Pawlak et al., 2004
plain
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data indicate that effects of dietary GI management are separable from effects of diabetes.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
hedged
In the paper
“consistent with the localization of drusen, a hallmark of AMD in humans (Ishibashi et al., 1998).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Ishibashi et al., 1998
plain
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This scheme proposes that under normal homeostatic conditions the UPS and LPS, functioning independently or in concert maintain the proteome (Figure 8, top).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This finding is consistent with the hypothesis that glycative stress results in the accumulation of oligomeric AGE modified ubiquitin conjugates.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
hedged
direct
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Enrichment of a lysosomal fraction is clearly indicated by observation of cathepsin D and lysosomal associated membrane protein (LAMP) in the lysosomal fraction (Figure S8A lanes 11-15) and not in the cytosolic fraction.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
boosted
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ability of the UPS and LPS in cultured RPE cells to clear AGEs, even after exposure to relatively high concentrations of MGO, is in keeping with the biological resiliency and function of these cells.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When sufficiently functional, these clearance mechanisms protect the RPE from the potential toxicity of AGEs.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
conditional
None of the sources cited for this claim have been checked yet.
In the paper
“Such limitations to the proteolytic capacities along with protein aggregation and insolubilization are etiologic for many common age-related diseases (Miyata et al., 1997; Sebekova et al., 1998; Kasper et al., 1999; Woltjer et al., 2003; Stitt, 2005; Bedford et al., 2008; Chen et al., 2009; Thornalley & Rabbani, 2009).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Miyata et al., 1997
- Not checked yetcites Sebekova et al., 1998
- Not checked yetcites Kasper et al., 1999
plain
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As diagramed in Figure 8, bottom, dicarbonyls or other sugar metabolites promote protein modification, aggregation and crosslinking.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, degrons, or amino acid residues that encode susceptibility for degradation on substrates may be blocked.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
conditional
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The accelerated and coincident accumulation of lesions and AGEs, including carbonyls (Figures 2, S1, S2), in animals that consumed the higher GI diet suggests that these are etiologically related.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
conditional
In the paper
“Our finding increased levels of ubiquitin conjugates in many age-related debilities, when cells confront chronic stress (Taylor et al., 2002)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Taylor et al., 2002
plain
correlational
None of the sources cited for this claim have been checked yet.
In the paper
“Delayed clearance of AGEs in the presence of the UPS and LPS inhibitors supports a role for both proteolytic pathways in their clearance as indicated for other types of altered proteins (Johnston et al., 1998; Kaganovich et al., 2008).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
What the sources say
- Not checked yetcites Johnston et al., 1998
- Not checked yetcites Kaganovich et al., 2008
hedged
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The accumulation of AGEs when autophagy was inhibited is consistent with a role for an autophagic LPS in removing AGEs.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
hedged
conditional
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the data inform that animals that consume the higher GI diets confront elevated glycative stress”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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In the paper
“recent reports that consuming lower GI diets is related to lower levels of glycation-related fluorescent products in the lens (Munch et al., 2011).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Munch et al., 2011
plain
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“diminishing such stress can be used to confer protection.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data suggest that the LPS is engaged upon AGE-accumulation-induced stress.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
hedged
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In the paper
“This inability of damaged proteins to reach an appropriate degradative compartment (the UPS in the cytosol or the lysosome) provides a novel additional explanation for the accumulation of insoluble ubiquitin conjugates and AGEs in many age-related syndromes including drusen and cataract (Jahngen-Hodge et al., 1992).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Jahngen-Hodge et al., 1992
plain
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the colocalization of AGEs in MG-H1-positive puncta with lysosomes when MGO-exposed cells are pretreated with proteasome or lysosomal inhibitors corroborates that an LPS is involved in degradation of AGEs (Figure S7, panels 3, 4, right).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The efficacy of the resin is demonstrated by our ability to recover a majority of the ubiquitin conjugates (Figure 7, lanes 5-8, bottom).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
boosted
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, such colocalization of ubiquitin conjugates and AGEs in lysosomes suggests that AGEs, some of which are conjugated to ubiquitin but not degraded by the UPS, are directed to the LPS for processing.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
hedged
direct
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insolubilization is a consequence of this stress.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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None of the sources cited for this claim have been checked yet.
In the paper
“conjugates increase in neurodegenerative disease and aging (Jahngen-Hodge et al., 1992; Crabb et al., 2002; Dudek et al., 2005; Bento et al., 2006; Shang, 2006; Maynard et al., 2009).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Jahngen-Hodge et al., 1992
- Not checked yetcites Crabb et al., 2002
- Not checked yetcites Dudek et al., 2005
plain
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The present results suggest that as with the UPS, glycative stress burdens the LPS, apparently shuttling more substrates to the lysosome.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
direct
None of the sources cited for this claim have been checked yet.
In the paper
“accumulation of AGEs during aging (Figure S1) (Ahmed et al., 2003; Morcos et al., 2008) appears to be an indicator of age-related decreased capacity of UPS and LPS (Zhang & Cuervo, 2008; Tonoki et al., 2009; Rodriguez et al.).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Ahmed et al., 2003
- Not checked yetcites Morcos et al., 2008
- Not checked yetcites Zhang & Cuervo, 2008
hedged
correlational
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Glycated ubiquitin may be incorporated into conjugates, rendering them less susceptible to degradation.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
conditional
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, these laboratory animal data provide in vivo corroboration of human epidemiologic associations between consuming lower GI diets and prolonged retinal health.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
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It may state two separate claims as one. 24
Probably not a substantial claim. 6

The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Furthermore, ubiquitin conjugates and AGEs accumulate and are found in lysosomes when cells are glycatively stressed or the UPS or LPS/autophagy are inhibited”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Abstract
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas addition of unmodified Ubc4 increased degradation by 80%, addition of the same amount of AGE-modified Ubc4 was less efficient (Figure 5D).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When cells were not glycatively stressed GFP was cleared within 4hrs (Figure 4A, top). However, upon imposition of glycative stress the GFP was stabilized (Figure 4A, bottom).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed that additional Wt-Ub increased degradation by ≥20% whereas addition of ubiquitin modified by G6P or MGO, decreased degradation of αA162 by ∼27 and 40%, respectively (Figure 5B).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Glycation induced reduction in UPS proteolytic activity
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar results were also obtained at 15 months of age (p=0.001 for difference between high and low GI groups, in another set of C57BL/6 mice and in 129SvPas mice (p=0.05)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > Consuming lower GI diets delays AMD-like lesions
plain
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, exposure of the cells to MGO resulted in a vast increase in AGEs in the lysates (Figure 7, lanes 2 and 4 vs. 1 and 3, top), as well as in the ubiquitin conjugate isolates (lanes 5-8).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By 14hrs levels of AGEs were declining (Figure 3B, Figure 6A lanes 7 vs. 2, Figure S6A lane 3 vs. 2) and this process continued such that by 20hrs relative levels of AGEs were only ≤70% the initial level (Figure 3B, Figure 6A lane 11 vs. 2).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
plain
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also found evidence that the LPS, including an autophagic LPS, is involved and cooperates with the UPS in removal of AGEs (Figures 4-6).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
direct
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These include deposition of basal deposits and loss of basal infoldings (Figure 1).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These, include AGEs that accumulated in lysosomes when the UPS was inhibited (Figure S7 panel 3 vs. 2) or when the LPS was inhibited (Figure S7 panel 4 vs. 2).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
plain
direct
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we demonstrated that AGE-modification of UPS substrates attenuates their degradation and results in their accumulation in aggregates (Figures 3-7).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
boosted
direct
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, when the LPS was inhibited there was 2.7 fold greater retention of AGEs in the NP40 insoluble fraction (lanes 6 vs. 4, right side) but only 25% more AGEs retained in the soluble fraction (lanes 6 vs. 4, left side).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
plain
direct
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“That the lesions delayed with dGI management are very early in the pathologic process is particularly attractive”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“However, it has been shown that relative to consuming higher GI diets, consuming lower GI diets is associated with attenuated blood glucose excursions, lower postprandial hypoglycemia/hyperlipidemia, lower insulinemia, less elevation of inflammatory markers and enhanced counter regulatory endocrine responses (Jenkins et al., 2002; Ludwig, 2002)”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Jenkins et al., 2002
- Not checked yetcites Ludwig, 2002
boosted
correlational
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Advanced glycation end products (AGEs) are formed when proteins are non enzymatically modified by carbohydrates or sugar metabolites, often with oxidative sequelle (Tessier et al., 1999; Ahmed et al., 2003; Thornalley et al., 2003; Glenn & Stitt, 2009).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Tessier et al., 1999
- Not checked yetcites Ahmed et al., 2003
- Not checked yetcites Thornalley et al., 2003
plain
direct
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“It has recently been demonstrated that the UPS and LPS collaborate in degradation of some proteins and that both proteolytic pathways are required to avoid protein insolubilization that is associated with neurodegeneration (Hara et al., 2006; Komatsu et al., 2006; Kwak et al., 2010; Hartl et al., 2011).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
What the sources say
- Not checked yetcites Hara et al., 2006
- Not checked yetcites Komatsu et al., 2006
- Not checked yetcites Kwak et al., 2010
boosted
direct
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“and that oxidative stress alters the function of the ubiquitin proteasome system (UPS) and limits cellular stress responses (Jahngen-Hodge et al., 1997; Shang et al., 1997; Shang et al., 2005; Shang & Taylor, 2011).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Jahngen-Hodge et al., 1997
- Not checked yetcites Shang et al., 1997
- Not checked yetcites Shang et al., 2005
plain
direct
It may state two separate claims as one.
In the paper
“Compounding stress and proteolytic burden to the retina and RPE, the retina is the most oxygenated and metabolically active tissue in the body (Warburg, 1924).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Warburg, 1924
plain
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Additional evidence that etiologically links accumulation of AGEs to dysfunction and aging is found in observations that maintaining a higher methylglyoxal (MGO) concentration is associated with shortened lifespan in C. elegans and increased apoptosis in cultured mammalian cells (Kuhla et al., 2006; Miller et al., 2006; Morcos et al., 2008; Guix et al., 2009; Ahmed et al., 2010).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Introduction
What the sources say
- Not checked yetcites Kuhla et al., 2006
- Not checked yetcites Miller et al., 2006
- Not checked yetcites Morcos et al., 2008
plain
correlational
It may state two separate claims as one.
In the paper
“These data indicate that upon glycative stress some AGEs are being transferred to the lysosome. Most fail to enter it. Rather, they associate with the membrane fraction, akin to tau F1 (Wang et al., 2009).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
What the sources say
- Not checked yetcites Wang et al., 2009
hedged
correlational
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Protein editing is unperturbed and AGEs and ubiquitin conjugates do not accumulate.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
plain
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these data provide the first indication that a UPS and LPS both play roles in the removal of AGEs and they indicate a dynamic flux of AGEs and ubiquitinated species between these compartments.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
hedged
direct
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Prolonged resistance to stress would appear essential for a postmitotic cell, such as the RPE, for which there are no options for replenishment.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, upon chronic glycative stress and/or aging these capacities are insufficient to maintain the proteome, and may themselves be diminished.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
conditional
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Prior literature and data from Figures 2-6, and S11, S8, S9 are consistent with glycative stress-induced accumulation of oligomers of AGEs, some of which are ubiquitinated or associated with ubiquitinated moieties.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
hedged
correlational
It may state two separate claims as one.
In the paper
“The autophagic pathway feeds into the LPS as autophagosomes fuse with lysosomes. (Klionsky et al., 2008).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Results > A UPS and an autophagic-LPS collaborate to remove AGEs
What the sources say
- Not checked yetcites Klionsky et al., 2008
plain
direct
Probably not a substantial claim.
In the paper
“it was predicted that consuming lower GI diets can save the sight of over 80,000 people in 5 years who would otherwise be blinded from AMD (Chiu et al., 2007c).”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
What the sources say
- Not checked yetcites Chiu et al., 2007c
plain
direct
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This situation is exacerbated by the accumulation of damaged proteins, which may diminish UPS efficacy, and induce oxidative stress, setting up a vicious cycle that results in additional stress and limited cellular function.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
conditional
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The stress may also alter the interaction between the UPS or LPS as one or both pathways are attenuated, and proteopoise is perturbed.”
§ Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics) > Discussion
hedged
conditional
It may state two separate claims as one.

29 of 29

The paper relies on this without support.
No pathobiochemical mechanism explaining why lower GI diets have salutary advantages is currently available.
“Pathobiochemical mechanisms that indicate why such critical salutary advantage is derived from lower GI diets are currently unavailable.”
The paper relies on this without support.
To date, consuming high GI diets has been associated only with accumulation of AGEs in blood.
“To date consuming high GI diets has been associated only with accumulation of AGEs in blood.”
The paper relies on this without support.
Most prior work regarding the effects of AGEs focused on extracellular and signaling events, leaving intracellular activities poorly understood.
“Most prior work regarding the effects of AGEs focused on extracellular and signaling events, leaving intracellular activities poorly understood.”
The paper relies on this without support.
There have been no studies that investigated or modeled the effects of consuming low or high GI diets on proteopoise.
“However, there have been no studies which investigated or modeled the effects of consuming low or high GI diets on proteopoise: defined here as the combined effects to the proteome of protein modification and altered proteolytic capacities.”
The paper relies on this without support.
Literature describing roles for each pathway and interactions between these proteolytic systems with regard to degradation of glycated proteins is scanty.
“However, literature that describes roles for each pathway as well as interactions between these proteolytic systems with regard to degradation of glycated proteins is scanty.”
The paper relies on this without support.
Levels of AGEs are determined by rates of formation and removal.
“Levels of AGEs are determined by rates of formation and removal.”
The paper relies on this without support.
There is a lack of suitable animal models of GI-disease relationships.
“the lack of suitable animal models of GI-disease relationships”
The paper relies on this without support.
There is an absence of established intracellular biochemical mechanisms that link epidemiologic data to AMD and several other widely prevalent age-related diseases.
“the absence of established intracellular biochemical mechanisms that link the epidemiologic data that indicates that consuming higher GI diets is related to higher risk for AMD and several other widely prevalent age-related diseases.”
The paper relies on this without support.
Consuming higher GI diets is related to higher risk for AMD and several other widely prevalent age-related diseases.
“consuming higher GI diets is related to higher risk for AMD and several other widely prevalent age-related diseases.”

9 of 9

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Self-citation
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · cited 1×
“…recently been demonstrated that the UPS and LPS collaborate in degradation of some proteins and that both proteolytic pathways are required to avoid protein insolubilization that is associated with neurodegeneration (Hara et al., 2006; Komatsu et al., 2006; Kwak et al., 2010; Hartl et al., 2011).”
Background
Glycemic index of foods: a physiological basis for carbohydrate exchange
Jenkins, D. J., Wolever, T. M., Taylor, R. H., Barker, H., Fielden, H., Baldwin, J. M., Bowling, A. C., Newman, H. C., Jenkins, A. L., & Goff, D. V. (1981) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/34.3.362 · Cited by 3,857 · cited 2×
“The GI quantifies available sugar in the blood within 2 h after eating 50 g of carbohydrate from a specific food in relation to blood sugar evoked by consuming 50 g of glucose or 50 g of white bread (Jenkins et al., 1981).”
Background
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · cited 1×
“…life-quality-limiting debilities including coronary heart disease (CHD), type 2 diabetes, and possibly age-related cataract even in nondiabetic subjects (Salmeron et al., 1997; Augustin et al., 2002; Chiu et al., 2007a,b, 2011; Krishnan et al., 2007; Mulholland et al., 2008; Chiu & Taylor, 2011).”
Background
Molecular chaperones in protein folding and proteostasis
Hartl, F. U., Bracher, A., & Hayer-Hartl, M. (2011) · Nature · doi:10.1038/nature10317 · Cited by 3,381 · cited 1×
“…recently been demonstrated that the UPS and LPS collaborate in degradation of some proteins and that both proteolytic pathways are required to avoid protein insolubilization that is associated with neurodegeneration (Hara et al., 2006; Komatsu et al., 2006; Kwak et al., 2010; Hartl et al., 2011).”
Background
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
Klionsky, D. J., Abeliovich, H., Agostinis, P., Agrawal, D. K., Aliev, G., Askew, D. S., Baba, M., Baehrecke, E. H., Bahr, B. A., Ballabio, A., et al. (2008) · Autophagy · doi:10.4161/auto.5338 · Cited by 2,230 · cited 1×
“…machinery, specifically the UPS and the autophagic lysosomal proteolytic system (LPS), and this dysfunction is associated with the accumulation of altered proteins, as seen upon aging of many types of cells and tissues (Ozdemir et al., 2008; Hamer et al., 2010; Hindle, 2010; Koga et al., 2011).”
Background
Impairment of the Ubiquitin-Proteasome System by Protein Aggregation
Bence, N., Sampat, R. M., & Kopito, R. R. (2001) · Science · doi:10.1126/science.292.5521.1552 · Cited by 2,209
Aggresomes: A Cellular Response to Misfolded Proteins
Johnston, J. A., Ward, C. L., & Kopito, R. R. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.7.1883 · Cited by 2,148
Dietary Fiber, Glycemic Load, and Risk of Non—insulin-dependent Diabetes Mellitus in Women
Salmerón, J. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540300040031 · Cited by 1,804 · cited 2×
“…life-quality-limiting debilities including coronary heart disease (CHD), type 2 diabetes, and possibly age-related cataract even in nondiabetic subjects (Salmeron et al., 1997; Augustin et al., 2002; Chiu et al., 2007a,b, 2011; Krishnan et al., 2007; Mulholland et al., 2008; Chiu & Taylor, 2011).”
Background
Untitled work
Ludwig (2002) · doi:10.1001/jama.287.18.2414 · Cited by 1,775 · cited 2×
“…is associated with attenuated blood glucose excursions, lower postprandial hypoglycemia ⁄ hyperlipidemia, lower insulinemia, less elevation of inflammatory markers, and enhanced counter regulatory endocrine responses (Jenkins et al., 2002; Ludwig, 2002), some of which have been related to AMD.”
Background

Show all 106 references

Research works printed but not linked: 5

Chiu CJ, 2007, Dietary glycemic index is related to progression of age‐related macular degeneration, Invest. Ophthalmol. Vis. Sci., 48, 2101
Chylack LT, 1994, Nuclear cataract: relative contributions to vision loss of opalescence and brunescence (abstract), Invest. Ophthalmol. Vis. Sci., 35, 42632
Shang F, 1995, Changes in ubiquitin conjugation activities in young and old lenses in response to oxidative stress, Inv. Ophthalmol. Vis. Sci., 36, S528
Warburg O, 1924, Improved method of measurement of respiration and glycosis, Biochem. Z., 152, 51
WeikelK TaylorA(2011)Nutritional modulation of cataract and age‐related macular degeneration. Duane’s Ophthalmology vol. 1 Philadelphia PA USA:Lippincott Williams and Wilkins.

Sorted by citations

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citation
Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex
Bhutto, I. A., & Lutty, G. A. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.04.005 · Cited by 1,028
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript i.e. RPE and BrMb appear to be dysfunctional first.”
Background
The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality
Chaudhuri, J., Bains, Y., Guha, S., Kahn, A., Hall, D., Bose, N., Gugliucci, A., & Kapahi, P. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.014 · Cited by 669
Advanced glycation end products
Gkogkolou, P., & Böhm, M. (2012) · Dermato-Endocrinology · doi:10.4161/derm.22028 · Cited by 613
Consequences of oxidative stress in age-related macular degeneration
Jarrett, S. G., & Boulton, M. E. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.03.009 · Cited by 549

See all 200

Authors: Uchiki, T., Weikel, K. A., Jiao, W., Shang, F., Caceres, A., Pawlak, D., Handa, J. T., Brownlee, M., Nagaraj, R., & Taylor, A.
Affiliations: Tufts University (US)
Boston Children's Hospital (US)
Johns Hopkins University (US)
Albert Einstein College of Medicine (US)
Case Western Reserve University (US)
Corresponding author: Taylor, Allen
ORCID: Weikel, Karen A.
Shang, Fu
Handa, James T.
Nagaraj, Ram
Taylor, Allen
Venue: Aging Cell
Publisher: Wiley
Published: 2011-11-15
Volume: 11
Issue: 1
Pages: 1-13
ISSN: 1474-9718 (ISSN-L)
1474-9726
DOI: 10.1111/j.1474-9726.2011.00752.x
PMC: PMC3257376
OpenAlex: W1501698769
Semantic Scholar: 5999b747d91388b28b15967143fbd004a9a7d1f0
Cited by: 200
References: 106
Citations by year: 2026: 6 · 2025: 9 · 2024: 10 · 2023: 13 · 2022: 8 · 2021: 21 · 2020: 14 · 2019: 14 · 2018: 18 · 2017: 15 · 2016: 11 · 2015: 16 · 2014: 12 · 2013: 13 · 2012: 18
FWCI: 8.41
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Aging Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Agriculture (1950‐510000‐060‐01A)
National Institutes of Health
U.S. Public Health Service (R01-13250, R01 21212)
National Eye Institute (R01EY021212, R01EY014005, R01 EY21212, R01 EY13250, R01EY013250, R01EY019904)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: glycemic index, advanced glycation end products, glycation stress, age-related macular degeneration, retinal lesions, ubiquitin-proteasome system, lysosomal proteolysis, autophagy, ubiquitin conjugation, aging, age-related diseases, glycemic load
MeSH terms: Aging, Animals, Autophagy, Cell-Free System, Diet, Disease Models, Animal, Glucose, Humans, Lysosomes, Macular Degeneration, Mice, Inbred C57BL, Retina, Severity of Illness Index, Glycation End Products, Advanced, Ubiquitin, Glycemic Index, Ubiquitin-Conjugating Enzymes, Proteasome Endopeptidase Complex, Mice

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Glycation‐altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age‐related disease (in nondiabetics)

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