The DOI matches its Crossref record; 106 of the 106 references it cites were found in a registry or an index; none of the 59 sources its claims cite is checked for support yet.
Glycation‐altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age‐related disease (in nondiabetics)
Open accessAbstract
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.
Overview
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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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50 Own result · 39 Own interpretation · 29 Not checked yet · 6 No basis given · 3 Own method
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- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Consuming lower GI diets delays AMD-like lesions · 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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Consuming lower GI diets delays AMD-like lesions · 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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § A UPS and an autophagic-LPS collaborate to remove AGEs · 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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § 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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Consuming lower GI diets delays AMD-like lesions · 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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Glycation induced reduction in UPS proteolytic activity · 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
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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- Asserted: passes — The authors put it forward as true.
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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
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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 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
plaindirect- Asserted: passes — The authors put it forward as true.
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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- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“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- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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 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
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
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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- Asserted: passes — The authors put it forward as true.
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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
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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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- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
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
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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.”
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?
In the citing paper
“Dietary AGEs promote AGE formation in the substantia nigra114.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [114]
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“…has been associated with cytotoxicity, we also sought information about whether glycative stress affected functions of the pathways in soluble or insoluble compartments of RPE (Jahngen-Hodge et al., 1992; Wang et al., 2007; Zhang et al., 2008; Gidalevitz et al., 2009; Salomons et al., 2009).”
BackgroundStructure and Mechanism of Formation of Human Lens Fluorophore LM-1
Tessier, F. J., Obrenovich, M. E., & Monnier, V. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20796 · Cited by 188
Cai, W., He, C., Zhu, L., Xue, C., Zheng, F., Striker, G. E., & Vlassara, H. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080152 · Cited by 188 · cited 2×
“Importantly, fasting insulin and fasting glucose were within normal ranges for aged mice, albeit that HOMA-IR levels were higher for the high GI-fed mice than the low GI-fed mice (Weikel, unpublished data) (Taguchi et al., 2007; Yau et al., 2007; Cai et al., 2008).”
BackgroundGlycemic index, glycemic load, and cereal fiber intake and risk of type 2 diabetes in US black women
Krishnan, S., Rosenberg, L., Singer, M., Hu, F. B., Djoussé, L., Cupples, L. A., & Palmer, J. R. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.21.2304 · Cited by 186 · cited 1×
“…in observations that maintaining a higher methylglyoxal (MGO) concentration is associated with shortened lifespan in Caenorhabditis 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).”
BackgroundAdvanced Glycation End Products in Age-related Macular Degeneration
Ishibashi, T. (1998) · Archives of Ophthalmology · doi:10.1001/archopht.116.12.1629 · Cited by 184 · cited 4×
“It was also shown that drusen in AMD patients contain ubiquitin conjugates (Ishibashi et al., 1998; Crabb et al., 2002) and that oxidative stress”
BackgroundInfluentialHypothesis: the ‘metabolic memory’, the new challenge of diabetes
Ihnat, M. A., Thorpe, J. E., & Ceriello, A. (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02138.x · Cited by 169
Dietary hyperglycemia, glycemic index and metabolic retinal diseases
Chiu, C., & Taylor, A. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2010.09.001 · Cited by 166 · 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).”
BackgroundSelf-citationTezel, G., Luo, C., & Yang, X. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0737 · Cited by 161 · cited 1×
“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).”
BackgroundShang, F., & Taylor, A. (1995) · Biochemical Journal · doi:10.1042/bj3070297 · Cited by 157 · cited 1×
“This may also overburden LPS capacities, further exacerbating cellular stress (Shang & Taylor, 1995; Shang et al., 1995, 1997; Martinez-Vicente et al., 2008; Zhang & Cuervo, 2008).”
BackgroundSelf-citationRoles of the Receptor for Advanced Glycation Endproducts in Diabetes-Induced Vascular Injury
Yonekura, H., Yamamoto, Y., Sakurai, S., Watanabe, T., & Yamamoto, H. (2005) · Journal of Pharmacological Sciences · doi:10.1254/jphs.cpj04005x · Cited by 148 · cited 1×
“…Ahmed et al., 2003; Vernace et al., 2007) as well as information regarding toxic properties of extracellular AGEs (Verbeke et al., 2000; Rosca et al., 2005; Yonekura et al., 2005; Yamada et al., 2006; Yao et al., 2007; Morcos et al., 2008; Glenn et al., 2009; Wei et al., 2009; Zhao et al., 2009).”
BackgroundNO signaling and S-nitrosylation regulate PTEN inhibition in neurodegeneration
Kwak, Y.-D., Ma, T., Diao, S., Zhang, X. Z., Chen, Y., Hsu, J., Lipton, S. A., Masliah, E., Xu, H., & Liao, F. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-49 · Cited by 142 · cited 1×
“…that express UPS reporters show the same diet–phenotype relationships that are indicated in this work, it would be informative to pursue comparable studies in such animals to elucidate how and why high GI diets reduce proteolytic capacity of the retina and other tissues (Lindsten et al., 2003).”
BackgroundZhao, Z., Zhao, C., Zhang, X. H., Zheng, F., Cai, W., Vlassara, H., & Ma, Z. A. (2009) · Endocrinology · doi:10.1210/en.2008-1342 · Cited by 132 · cited 1×
“…Ahmed et al., 2003; Vernace et al., 2007) as well as information regarding toxic properties of extracellular AGEs (Verbeke et al., 2000; Rosca et al., 2005; Yonekura et al., 2005; Yamada et al., 2006; Yao et al., 2007; Morcos et al., 2008; Glenn et al., 2009; Wei et al., 2009; Zhao et al., 2009).”
BackgroundProtein modification and replicative senescence of WI‐38 human embryonic fibroblasts
Ahmed, E. K., Rogowska-Wrzesińska, A., Roepstorff, P., Bulteau, A., & Friguet, B. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00555.x · Cited by 132 · cited 3×
“methylglyoxal (MGO) concentration is associated with shortened lifespan in Caenorhabditis 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).”
BackgroundInfluentialTian, J. Y., Ishibashi, K., Ishibashi, K., Reiser, K. M., Grebe, R. R., Biswal, S. S., Gehlbach, P. L., & Handa, J. T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504759102 · Cited by 130 · cited 1×
“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).”
BackgroundSelf-citationBulteau, A., Verbeke, P., Petropoulos, I., Chaffotte, A., & Friguet, B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105374200 · Cited by 128 · cited 1×
“H) (Takizawa et al., 1993; Suarez et al., 1995; Bulteau et al., 2001).”
The role of advanced glycation end products in retinal ageing and disease
Glenn, J. V., & Stitt, A. W. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.04.016 · Cited by 127 · cited 2×
“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).”
BackgroundThe Maillard Reaction in Eye Diseases
Stitt, A. W. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1338.066 · Cited by 127 · cited 2×
“…the proteolytic capacities along with protein aggregation and insolubilization are etiologic for many common agerelated 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).”
BackgroundYau, J. L. W., McNair, K., Noble, J., Brownstein, D. G., Hibberd, C. J., Morton, N. M., Mullins, J. J., Morris, R., Cobb, S., & Seckl, J. R. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2190-07.2007 · Cited by 116 · cited 1×
“Importantly, fasting insulin and fasting glucose were within normal ranges for aged mice, albeit that HOMA-IR levels were higher for the high GI-fed mice than the low GI-fed mice (Weikel, unpublished data) (Taguchi et al., 2007; Yau et al., 2007; Cai et al., 2008).”
Backgroundα-Synuclein Protofibrils Inhibit 26 S Proteasome-mediated Protein Degradation
Zhang, N., Tang, Z., & Liu, C.-W. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710560200 · Cited by 116 · cited 1×
“…has been associated with cytotoxicity, we also sought information about whether glycative stress affected functions of the pathways in soluble or insoluble compartments of RPE (Jahngen-Hodge et al., 1992; Wang et al., 2007; Zhang et al., 2008; Gidalevitz et al., 2009; Salomons et al., 2009).”
BackgroundAging and regulated protein degradation: who has the UPPer hand?
Vernace, V. A., Schmidt‐Glenewinkel, T., & Figueiredo‐Pereira, M. E. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00329.x · Cited by 110 · cited 2×
“, cataract in lens, neurodegeneration in aging brain) (Sasaki et al., 1998; Ahmed et al., 2003; Vernace et al., 2007) as well as”
BackgroundYamada, Y., Ishibashi, K., Ishibashi, K., Bhutto, I. A., Tian, J. Y., Lutty, G. A., & Handa, J. T. (2006) · Experimental Eye Research · doi:10.1016/j.exer.2005.10.005 · Cited by 108 · cited 1×
“…Ahmed et al., 2003; Vernace et al., 2007) as well as information regarding toxic properties of extracellular AGEs (Verbeke et al., 2000; Rosca et al., 2005; Yonekura et al., 2005; Yamada et al., 2006; Yao et al., 2007; Morcos et al., 2008; Glenn et al., 2009; Wei et al., 2009; Zhao et al., 2009).”
BackgroundSelf-citationAmyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation
Guix, F. X., ILL‐Raga, G., Bravo, R., Nakaya, T., Fabritiis, G. D., Coma, M., Miscione, G. P., Villà-Freixa, J., Suzuki, T., Fernàndez‐Busquets, X., et al. (2009) · Brain · doi:10.1093/brain/awp023 · Cited by 107 · cited 3×
“methylglyoxal (MGO) concentration is associated with shortened lifespan in Caenorhabditis 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).”
BackgroundInfluentialA photoconvertible reporter of the ubiquitin-proteasome system in vivo
Hamer, G., Matilainen, O., & Holmberg, C. I. (2010) · Nature Methods · doi:10.1038/nmeth.1460 · Cited by 104 · 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).”
BackgroundMiller, A. G., Smith, D. G., Bhat, M. B., & Nagaraj, R. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513813200 · Cited by 103 · cited 2×
“methylglyoxal (MGO) concentration is associated with shortened lifespan in Caenorhabditis 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).”
BackgroundSelf-citationGlenn, J. V., Mahaffy, H., Wu, K., Smith, G., Nagai, R., Simpson, D. A. C., Boulton, M. E., & Stitt, A. W. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-1724 · Cited by 102 · cited 2×
“information regarding toxic properties of extracellular AGEs (Verbeke et al., 2000; Rosca et al., 2005; Yonekura et al., 2005; Yamada et al., 2006; Yao et al., 2007; Morcos et al., 2008; Glenn et al., 2009; Wei et al., 2009; Zhao et al., 2009).”
BackgroundChiu, C., Milton, R. C., Gensler, G. R., & Taylor, A. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.1.180 · Cited by 101 · 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).”
BackgroundSelf-citationInforming food choices and health outcomes by use of the dietary glycemic index
Chiu, C., Liu, S., Willett, W. C., Wolever, T. M. S., Brand-Miller, J. C., Barclay, A. W., & Taylor, A. (2011) · Nutrition Reviews · doi:10.1111/j.1753-4887.2011.00382.x · Cited by 101 · cited 4×
“Additional hypotheses regarding glycemic stress when the retina confronts hypoxia have been offered (Chiu et al., 2011).”
BackgroundInfluentialSelf-citationMaynard, C. J., Böttcher, C., Ortega, Z., Smith, R. A., Florea, B. I., Dı́az-Hernández, M., Brundin, P., Overkleeft, H. S., Li, J., Lucas, J. J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906463106 · Cited by 98 · cited 1×
“This raised concern because 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 et al., 2006; Maynard et al., 2009).”
BackgroundChiu, C., Milton, R. C., Klein, R., Gensler, G. R., & Taylor, A. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.4.1210 · Cited by 93 · 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).”
BackgroundSelf-citationDudek, E. J., Shang, F., Liu, Q. L., Valverde, P., Hobbs, M., & Taylor, A. (2005) · The FASEB Journal · doi:10.1096/fj.05-4049fje · Cited by 86 · cited 3×
“the UPS (Dudek et al., 2005; Zetterberg et al., 2006; Zhang et al., 2007), and we anticipated that glycation would also enhance susceptibility of AGEs to degradation in systems with a fully functional UPS.”
BackgroundSelf-citationMulholland, H. G., Murray, L., Cardwell, C. R., & Cantwell, M. M. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604496 · Cited by 84 · 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).”
BackgroundNutritional and Environmental Influences on the Eye
McLaren, D. S. (2000) · Nutrition · doi:10.1016/s0899-9007(00)00388-9 · Cited by 83
Farboud, B., Aotaki-Keen, A. E., Miyata, T., Hjelmeland, L. M., & Handa, J. T. (1999) · PubMed · Cited by 80
Self-citationRetinal pigment epithelial cell distribution in central retina of rhesus monkeys.
Snodderly, D. M., Sandstrom, M. M., Leung, I. Y.-F., Zucker, C. L., & Neuringer, M. D. (2002) · PubMed · Cited by 79
Lys6-modified Ubiquitin Inhibits Ubiquitin-dependent Protein Degradation
Shang, F., Deng, G., Liu, Q., Guo, W., Haas, A. L., Crosas, B., Finley, D., & Taylor, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414356200 · Cited by 74 · cited 3×
“S9B) (Shang et al., 2005).”
BackgroundSelf-citationWoltjer, R. L., Maezawa, I., Ou, J. J., Montine, K. S., & Montine, T. J. (2004) · Journal of Alzheimer s Disease · doi:10.3233/jad-2003-5607 · Cited by 70 · cited 1×
“…the proteolytic capacities along with protein aggregation and insolubilization are etiologic for many common agerelated 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).”
Selective Accumulation of Aggregation-Prone Proteasome Substrates in Response to Proteotoxic Stress
Salomons, F. A., Menéndez-Benito, V., Böttcher, C., McCray, B. A., Taylor, J. P., & Dantuma, N. P. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01485-08 · Cited by 69 · cited 2×
“…has been associated with cytotoxicity, we also sought information about whether glycative stress affected functions of the pathways in soluble or insoluble compartments of RPE (Jahngen-Hodge et al., 1992; Wang et al., 2007; Zhang et al., 2008; Gidalevitz et al., 2009; Salomons et al., 2009).”
BackgroundThornalley, P. J., & Rabbani, N. (2009) · Seminars in Dialysis · doi:10.1111/j.1525-139x.2009.00589.x · Cited by 68 · cited 1×
“…the proteolytic capacities along with protein aggregation and insolubilization are etiologic for many common agerelated 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).”
BackgroundScribner, K. B., Pawlak, D. B., Aubin, C. M., Majzoub, J. A., & Ludwig, D. S. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90487.2008 · Cited by 66 · cited 2×
“established in humans and other mouse models (Jenkins et al., 2002; van Schothorst et al., 2008; Scribner et al., 2008; Isken et al., 2009).”
BackgroundSelf-citationUbiquitin and ubiquitin conjugates in human lens
Jahngen-Hodge, J., Cyr, D. E., Laxman, E., et al. (1992) · Experimental Eye Research · doi:10.1016/0014-4835(92)90016-l · Cited by 62 · cited 7×
“…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).”
BackgroundInfluentialSelf-citationVlassara, H., Uribarri, J., Ferrucci, L., Cai, W., Torreggiani, M., Post, J. B., Zheng, F., & Striker, G. E. (2009) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2009.07.013 · Cited by 60 · cited 1×
“…Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 1 Aging Cell (2012) 11, pp1–13 Doi: 10.1111/j.1474-9726.2011.00752.x Ag in g Ce ll 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).”
BackgroundInfluentiald-Ribosylated Tau forms globular aggregates with high cytotoxicity
Chen, L., Yan, W., Wang, X., & He, R. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0058-7 · Cited by 59 · cited 2×
“…the proteolytic capacities along with protein aggregation and insolubilization are etiologic for many common agerelated 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).”
BackgroundBento, C. F., Marques, F., Fernandes, R., & Pereira, P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013007 · Cited by 59 · cited 1×
“This raised concern because 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 et al., 2006; Maynard et al., 2009).”
BackgroundVerbeke, P., Perichon, M., Friguet, B., & Bakala, H. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00071-5 · Cited by 53 · cited 2×
“information regarding toxic properties of extracellular AGEs (Verbeke et al., 2000; Rosca et al., 2005; Yonekura et al., 2005; Yamada et al., 2006; Yao et al., 2007; Morcos et al., 2008; Glenn et al., 2009; Wei et al., 2009; Zhao et al., 2009).”
BackgroundGoligorsky, M. S., Chen, J., & Patschan, S. A. (2009) · Current Opinion in Hematology · doi:10.1097/moh.0b013e32832a07bd · Cited by 50 · cited 1×
“…Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 1 Aging Cell (2012) 11, pp1–13 Doi: 10.1111/j.1474-9726.2011.00752.x Ag in g Ce ll 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).”
BackgroundInfluentialMoheimani, F., Morgan, P. E., van Reyk, D. M., & Davies, M. J. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.02.007 · Cited by 48 · cited 2×
“…that AGE modification might convert UPS substrates into competitive inhibitors of the proteasome, in effect limiting – and rendering insufficient – the amount of available proteasome even under stress conditions when the proteasome retains its activity (Bence et al., 2001; Moheimani et al., 2010).”
Backgroundvan Schothorst, E. M., Bunschoten, A., Schrauwen, P., Mensink, R. P., & Keijer, J. (2008) · The FASEB Journal · doi:10.1096/fj.08-117119 · Cited by 47 · cited 1×
“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; van Schothorst et al., 2008; Scribner et al., 2008; Isken et al., 2009).”
BackgroundPathological effects of glyoxalase I inhibition in SH‐SY5Y neuroblastoma cells
Kuhla, B., Lüth, H., Haferburg, D., Weick, M., Reichenbach, A., Arendt, T., & Münch, G. W. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20838 · Cited by 43 · 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).”
BackgroundŠebeková, K., Schinzel, R., Ling, H., Simm, A., Xiang, G., Gekle, M., Münch, G. W., Vamvakas, S., & Heidland, A. (1998) · PubMed · Cited by 43
Miyata, S., Liu, B.-F., Shoda, H., Ohara, T., Yamada, H., Suzuki, K., & Kasuga, M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.7.4037 · Cited by 37 · cited 2×
“Such limitations to the proteolytic capacities along with protein aggregation and insolubilization are etiologic for many common agerelated 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).”
BackgroundIsken, F., Weickert, M. O., Tschöp, M. H., Nogueiras, R., Möhlig, M., Abdelrahman, A., Klaus, S., Thorens, B., & Pfeiffer, A. F. (2009) · Diabetologia · doi:10.1007/s00125-009-1466-9 · Cited by 36 · cited 2×
“established in humans and other mouse models (Jenkins et al., 2002; van Schothorst et al., 2008; Scribner et al., 2008; Isken et al., 2009).”
BackgroundMolecular mechanisms of proteasome plasticity in aging
Rodriguez, K. A., Gaczynska, M. E., & Osmulski, P. A. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.01.002 · Cited by 34 · cited 1×
“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., 2010).”
BackgroundTakizawa, N., Takada, K., & Ohkawa, K. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1471 · Cited by 33 · cited 1×
“H) (Takizawa et al., 1993; Suarez et al., 1995; Bulteau et al., 2001).”
Caceres, A., Shang, F., Wawrousek, E. F., Liu, Q., Avidan, O., Cvekl, A., Yang, Y., Haririnia, A., Storaska, A. J., Fushman, D., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013331 · Cited by 33 · cited 1×
“5B, lane 3) (Shang et al., 2005; Caceres et al., 2010).”
Self-citationDegradation of C-terminal Truncated αA-crystallins by the Ubiquitin–Proteasome Pathway
Zhang, X., Dudek, E. J., Liu, B.-F., et al. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0196 · Cited by 28 · cited 1×
“…modified and mutated proteins are often preferred substrates for degradation, particularly by the UPS (Dudek et al., 2005; Zetterberg et al., 2006; Zhang et al., 2007), and we anticipated that glycation would also enhance susceptibility of AGEs to degradation in systems with a fully functional…”
BackgroundSelf-citationSuárez, G., Etlinger, J. D., Maturana, J., et al. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1387 · Cited by 27 · cited 1×
“H) (Takizawa et al., 1993; Suarez et al., 1995; Bulteau et al., 2001).”
Zetterberg, M., Zhang, X., Taylor, A., Liu, B.-F., Liang, J. J. ‐., & Shang, F. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-1664 · Cited by 27 · cited 2×
“3D), a hallmark for the UPS (Hershko & Ciechanover, 1986; Zetterberg et al., 2006).”
BackgroundSelf-citationTaylor, A., Shang, F., Nowell, T., Galanty, Y., & Shiloh, Y. (2002) · Oncogene · doi:10.1038/sj.onc.1205557 · Cited by 24 · cited 2×
“Our finding increased levels of ubiquitin conjugates in many agerelated debilities, when cells confront chronic stress (Taylor et al., 2002), and in glycatively stressed RPE may appear counter intuitive if glycation or”
BackgroundSelf-citationThyberg, J., & Blomgren, K. (1999) · PubMed · Cited by 24
Ozdemir, A. M., Hopfer, U., Rosca, M. G., Fan, X.-J., Monnier, V. M., & Weiss, M. F. (2007) · American Journal of Nephrology · doi:10.1159/000108757 · Cited by 23 · 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).”
BackgroundKasper, M., Schinzel, R., Niwa, T., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0902 · Cited by 19
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Metadata
- 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
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2011-11-15
- Volume
- 11
- Issue
- 1
- Pages
- 1-13
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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