The DOI matches its Crossref record; 176 of the 177 references it cites were found in a registry or an index; 31 of the 61 sources its claims cite were checked for support.
Protein Homeostasis and Aging: the importance of exquisite quality control
Open accessAbstract
All cells count on precise mechanisms that regulate protein homeostasis to maintain a stable and functional proteome. A progressive deterioration in the ability of cells to preserve the stability of their proteome occurs with age and contributes to the functional loss characteristic of old organisms. Molecular chaperones and the proteolytic systems are responsible for this cellular quality control by assuring continuous renewal of intracellular proteins. When protein damage occurs, such as during cellular stress, the coordinated action of these cellular surveillance systems allows detection and repair of the damaged structures or, in many instances, leads to the complete elimination of the altered proteins from inside cells. Dysfunction of the quality control mechanisms and intracellular accumulation of abnormal proteins in the form of protein inclusions and aggregates occur in almost all tissues of an aged organism. Preservation or enhancement of the activity of these surveillance systems until late in life improves their resistance to stress and is sufficient to slow down aging. In this work, we review recent advances on our understanding of the contribution of chaperones and proteolytic systems to the maintenance of cellular homeostasis, the cellular response to stress and ultimately to longevity.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that age-related deterioration of protein quality control—molecular chaperones and proteolytic systems such as the ubiquitin/proteasome system and autophagy—contributes to loss of proteostasis and aging. Preserving or enhancing these surveillance systems can improve stress resistance and slow aging in model organisms.
Key findings
- Chaperones are central “gate keepers” of protein quality control; cytosolic sHSP and hsp70 family members are highly conserved (up to 50% amino acid identity among species), and their overexpression confers heat-shock resistance and stress tolerance in flies.
- Aging impairs chaperone responses: decreased hsp70 transcriptional upregulation occurs in senescent fibroblasts and old tissues across species up to monkeys, linked to HSF inability to bind the heat shock element; caloric restriction restores chaperone response, and cells from human centenarians preserve chaperone upregulation during stress.
- Longevity is linked to chaperones and proteolysis: extra copies of an hsp-70 family member or sHSPs make flies and worms long-lived, HSF overexpression increases nematode lifespan, and CHIP-defective mice have reduced longevity with accelerated aging, higher damaged proteins, and declined proteasome activity.
- Proteolytic systems decline with age: proteasome activity decreases in several tissues though not universally; CMA activity decreases in almost all tissues of old rodents and senescent human fibroblasts due to lower LAMP-2A; restoring CMA in mouse liver improves cellular homeostasis, stress response, and liver function comparable to young mice.
Methods
- Narrative review of recent advances; no primary experimental data, sample, or new analysis. It synthesizes biochemical and genetic studies in yeast, worms, flies, rodents, human cells/tissues, and centenarians.
- Discusses molecular chaperones (HSP families and organelle-specific chaperones), the ubiquitin/proteasome system, and autophagic/lysosomal pathways (macroautophagy, microautophagy, and chaperone-mediated autophagy) and their age-related changes and connections to longevity.
Limitations
- Stated: broad lack of knowledge on tissue-dependent characteristics of the proteostasis network and cross-talk among organs/tissues; species-specific differences (e.g., CMA is absent or has different components in unicellular organisms and invertebrates); need for genetic models with late-life impairment and better chemical modulators.
- Evident: as a narrative review, it does not systematically search or quantitatively synthesize evidence; many conclusions rely on diverse model systems and cited studies rather than uniform outcome measures.
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Claims the paper makes
31 of 61 cited sources checked · 18 supported · 1 flagged · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Activation of macroautophagy is a common feature of all the long-lived mutant worms, including the models for dietary restriction (Hansen et al., 2008; Hars et al., 2007; Melendez et al., 2003; Tóth et al., 2008).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Disputedcites Hansen et al., 2008 sourceExperimental — accuracy not yet measured
The Results and Discussion support increased autophagy in long-lived dietary-restriction eat-2 mutants. But the Discussion reports no increase in the autophagy reporter’s foci in long-lived rsks-1 mutants, contrary to the claim that activation is a feature of all long-lived mutant worms. The authors note that autophagy in other tissues remains possible. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
- Partly supportedcites Hars et al., 2007 sourceExperimental — accuracy not yet measured
The paper’s Abstract reports that knocking down autophagy genes shortened the lifespan of long-lived daf-2 mutant worms, supporting a role for autophagy in their longevity. It does not show that macroautophagy is activated in all long-lived mutant worms or address dietary-restriction models; searches for dietary restriction and autophagy activation found no such result. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites Melendez et al., 2003 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Numerous studies support now that increased chaperone induction leads to increased longevity both in uni- and multicellular organisms (Lithgow et al., 1995; Shama et al., 1998; Tatar et al., 1997).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 3. Molecular Chaperones in protein quality control > 3.3. Molecular chaperones in longevity and aging
What the sources say
- Partly supportedcites Lithgow et al., 1995 sourceExperimental — accuracy not yet measured
The Results and Discussion report that mild thermal stress increased both thermotolerance and lifespan in C. elegans, a multicellular organism. But the Discussion treats lifespan extension through increased heat-shock-protein expression as a model and explicitly says that the causal prediction still needs testing. This paper does not establish the claimed effect of chaperone induction or report it in unicellular organisms. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites Shama et al., 1998 source
- Not checked — no full text of the sourcecites Tatar et al., 1997 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“and an E3 ligase (Hawse et al., 2004) have been reported in some aged tissues.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
What the sources say
- Could not verifycites Hawse et al., 2004 sourceExperimental — accuracy not yet measured
Section 3 (page unavailable) reports transcripts with decreased expression in aged human lens epithelia, but does not identify an E3 ligase among them. Searches for “E3,” “ligase,” and “ubiquitin” found no passage in our copy establishing age-related downregulation of an E3 ligase. (LLM, conf=0.73)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The increased content with age of mutant forms of ubiquitin due to molecular misreading could also be behind the inefficient clearance of polyubiquitinated proteins in aging (Tsirigotis et al., 2001).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
What the sources say
- Partly supportedcites Tsirigotis et al., 2001 sourceExperimental — accuracy not yet measured
The indexed passage labeled Abstract (page unavailable) reports that engineered K48R mutant ubiquitin-expressing cells accumulated high-molecular-weight ubiquitin conjugates and showed impaired proteolysis. It does not establish that mutant ubiquitin increases with age through molecular misreading or that this explains inefficient clearance in aging. (LLM, conf=0.86)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“studies in CHIP defective mice also support an important role for the UPS in longevity and health-span (Min et al., 2008)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
What the sources say
- Supportedcites Min et al., 2008 source
The Results report significantly reduced longevity in CHIP-deficient mice. The Discussion reports decreased UPS function alongside accelerated aging phenotypes and proposes impaired protein quality control as a possible mechanism affecting longevity. This supports the citing sentence’s qualified claim about longevity and health-span. (LLM, conf=0.90)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“mutations in the genes of the CUL-1 E3 ligase complex shorten the extended lifespan of different insulin signaling C. elegans mutants (Ghazi et al., 2007)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
What the sources say
- Partly supportedcites Ghazi et al., 2007 sourceExperimental — accuracy not yet measured
The Results report that RNAi depletion of cul-1 and skr-1/2 shortened the extended lifespan of several daf-2 mutant strains, and that a lin-23 mutation reduced lifespan extension in daf-2 mutants. The claim captures the lifespan finding but overstates the mutation evidence: the paper tested mutations in one CUL-1 complex gene, while it used RNAi to reduce the others. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the activity of other quality control mechanisms, such as macroautophagy and the UPS, is also improved in these animals (Zhang and Cuervo, 2008)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Supportedcites Zhang and Cuervo, 2008 source
The paper reports indirect evidence of improved macroautophagy in the livers of aged transgenic mice (passage 8, section labeled Abstract). It also reports that age-related declines in proteasome activity were absent in those mice and describes improved functioning of the proteolytic systems (passage 1, same section). (LLM, conf=0.92)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“studies by other groups in worms and flies seem to support that functional macroautophagy is necessary to preserve normal lifespan (Juhasz et al., 2007; Morck and Pilon, 2006; Simonsen et al., 2007)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Supportedcites Juhasz et al., 2007 source
The Results section reports that loss of Atg7 reduced the lifespan of flies under normal conditions (Fig. 3E). The Abstract identifies Atg7 as a core autophagy regulator and says the mutants have severe autophagy defects. This paper supports the fly portion of the multi-citation claim; it does not need to establish the worm portion. (LLM, conf=0.93)
- Partly supportedcites Morck and Pilon, 2006 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) links increased autophagy in feeding-defective C. elegans mutants with increased longevity, but describes a role for autophagy in longevity as proposed. It does not show that functional autophagy is necessary to preserve normal lifespan. Its mention of flies in the Background concerns starvation-induced autophagy, not lifespan. (LLM, conf=0.84)
- Supportedcites Simonsen et al., 2007 source
In the paper’s discussion of Bchs-modifier mutants (page not supplied), Atg8a is identified as an autophagy-related gene, and Atg8a mutants are reported to have reduced adult lifespans in flies. This supports the fly portion of the multi-citation claim; the paper need not supply the worm evidence attributed collectively to the other citations. (LLM, conf=0.90)
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The lifespan extension observed in worms mutant for the equivalent of the insulin-signaling pathway, such as daf-2, is drastically reduced when macroautophagy genes are knocked down (Hars et al., 2007; Melendez et al., 2003).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Supportedcites Hars et al., 2007 source
The results in the section labeled Abstract report that knocking down the autophagy genes atg-7 or atg-12 significantly shortened the lifespan of daf-2 mutant worms. Mean lifespan fell from about 18 days in controls to 13 or 11 days, respectively, supporting the claimed substantial reduction without implying that the lifespan advantage was eliminated. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites Melendez et al., 2003 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Functional macroautophagy has also proven necessary to attain the maximal lifespan extension mediated by mutations in other genes such as the nutrient-sensor TOR (Hansen et al., 2008), the tumor suppressor protein p53 (Tavernarakis et al., 2008) and even the lifespan prolonging effect of Sirt-1 (Morselli et al., 2010).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Supportedcites Hansen et al., 2008 source
Hansen et al. is cited for the TOR portion of the sentence, not the separately cited p53 or Sirt-1 portions. The Discussion (page not provided) states that autophagy genes are required for lifespan extension in TOR-pathway mutants. (LLM, conf=0.93)
- Supportedcites Tavernarakis et al., 2008 source
The p53 citation supports the p53 portion of the sentence, not the separately cited TOR or Sirt-1 portions. The Abstract reports that depleting the autophagy protein BEC-1 reduced the extended lifespan of C. elegans cep-1 mutants to approximately normal levels. (LLM, conf=0.93)
- Supportedcites Morselli et al., 2010 source
The citation to Morselli et al. is attached to the Sirt-1 portion of the sentence, not the TOR or p53 portions. In the section “The life span-prolonging effect of sirtuin-1 is mediated by autophagy” (page unavailable), the paper reports that sir-2.1 overexpression extends median and maximum lifespan in C. elegans, but that this gain is lost when the essential autophagy gene bec-1 is knocked down. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
- It may state two separate claims as one. 17
- Probably not a substantial claim. 7
Every source the paper cites for this claim was checked and supports it.
In the paper
“worms lacking AIP-1, a homologue of the regulatory mammalian subunit AIRAP, exhibit shortened lifespan and hypersensitivity to misfolding proteins (Yun et al., 2008)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
What the sources say
- Supportedcites Yun et al., 2008 source
The Results report that aip-1 RNAi shortened mean worm lifespan from 16.6 to 10.6 days and accelerated paralysis caused by a misfolding-prone amyloid peptide. The paper identifies worm aip-1 as a homologue of mammalian AIRAP, a component of the proteasome’s 19S regulatory cap. The supplied passages do not provide page numbers. (LLM, conf=0.94)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we have found that the activity of this autophagic pathway decreases in almost all tissues of old rodents and in senescent human fibroblasts in culture (Cuervo and Dice, 2000; Dice, 1982)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Partly supportedcites Cuervo and Dice, 2000 sourceExperimental — accuracy not yet measured
The Introduction says chaperone-mediated autophagy decreases in most tissues of old organisms, and the Discussion reports a decrease in senescent human fibroblasts in culture. The paper's own rodent results concern rat liver; it does not establish a decrease in almost all tissues of old rodents. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites Dice, 1982 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“marked increase in lifespan and enhance health-span in mice treated with rapamycin, a well-characterized inhibitor of mTOR (Harrison et al., 2009)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Partly supportedcites Harrison et al., 2009 sourceExperimental — accuracy not yet measured
The Abstract (page not provided) reports that rapamycin inhibits the mTOR pathway and extends median and maximal lifespan in male and female mice. It does not establish enhanced health-span: disease patterns did not differ from controls, and the authors say that determining whether ageing was slowed would require testing age-dependent changes in multiple tissues and processes. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Livers of mice with preserved CMA function show better cellular homeostasis, improved ability to respond to the cell damage induced by different stressors and their liver function is comparable to that of young mice (Zhang and Cuervo, 2008).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Supportedcites Zhang and Cuervo, 2008 source
The paper’s main text (indexed under Abstract; page unavailable) reports improved cellular homeostasis and ability to buffer cellular damage in aged mice with preserved CMA. It also reports that their recovery times in a liver-function assay were indistinguishable from those of young wild-type mice. The reference to different stressors is a broad paraphrase of the paper’s discussion of CMA responses to starvation, oxidation and other protein-damaging conditions. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Three different forms of autophagy have been described in mammalian cells: macroautophagy, microautophagy and chaperone-mediated autophagy (Fig. 3) (Cuervo, 2009; He and Klionsky, 2009; Mizushima et al., 2008).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Supportedcites Cuervo, 2009 source
The section “Autophagy: Cellular self-digestion with a purpose” states that three mechanisms coexist in most mammalian cells and names macroautophagy, microautophagy, and chaperone-mediated autophagy. The copy does not provide a page number for this passage. (LLM, conf=0.94)
- Partly supportedcites He and Klionsky, 2009 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes autophagosomes in mammalian cells, supporting the macroautophagy portion of the claim. Our copy does not identify microautophagy or chaperone-mediated autophagy as the other two forms, or state the three-part classification (searched both terms and the three-form phrasing). (LLM, conf=0.84)
- Supportedcites Mizushima et al., 2008 source
The Abstract lists microautophagy, macroautophagy and chaperone-mediated autophagy as types of autophagy. Figure 1, “Different types of autophagy,” describes all three, supporting the cited classification; the supplied passages do not give page numbers. (LLM, conf=0.93)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“recent work in flies has shown that expression of specific autophagy genes prolongs lifespan and provides resistance to particular stressors (Simonsen et al., 2007)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Partly supportedcites Simonsen et al., 2007 sourceExperimental — accuracy not yet measured
The paper reports in its Abstract that mutations in several autophagy-related genes reduce adult fly lifespan, and its starvation-response section reports increased starvation sensitivity in atg8a mutants. These findings link the genes to longevity and stress response, but the paper does not show that expressing those genes prolongs lifespan or increases stress resistance. Its Bchs overexpression experiment concerns an eye phenotype, not either claimed benefit. (LLM, conf=0.83)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
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 two main components of this pathway, the ubiquitinization machinery – responsible for substrate targeting – and the proteasome core – where degradation takes place, undergo age-dependent changes that contribute to the lower efficiency of this system in old organisms and the consequent alterations in proteostasis.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“They have demonstrated the existence of a pool of metastable proteins in all cells, highly dependent on chaperones for their normal folding and function, and how these proteins can become unstable and aggregate in the presence of additional pathogenic proteins, such as those altered in protein conformational disorders (Gidalevitz et al., 2006).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 3. Molecular Chaperones in protein quality control > 3.3. Molecular chaperones in longevity and aging
What the sources say
- Not checked — no full text of the sourcecites Gidalevitz et al., 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Many reports have shown different degrees of decrease in the activity of the proteasome with age in several tissues, although, in contrast to the lysosomal system, the decline in activity with age does not seem to be universal (Carrard et al., 2003; Ferrington et al., 2005; Keller et al., 2000 b; Shibatani et al., 1996).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
What the sources say
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Dysfunction of the quality control mechanisms and intracellular accumulation of abnormal proteins in the form of protein inclusions and aggregates occur in almost all tissues of an aged organism.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
In the paper
“In other tissues, constitutive levels of these enzymes are higher in the old animals that instead fail to upregulate their activity in response to stressors (Scrofano et al., 1998a)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.1. The ubiquitin/proteasome system
What the sources say
- Not checked — no full text of the sourcecites Scrofano et al., 1998a source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Preservation or enhancement of the activity of these surveillance systems until late in life improves their resistance to stress and is sufficient to slow down aging.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt 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
“CMA is absent, or at least does not have the same components in unicellular organisms and invertebrates.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 5. Concluding remarks and the many open paths ahead
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. 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
“The components of the quality control mechanisms are highly conserved through evolution, however, species-specific differences should be expected.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 5. Concluding remarks and the many open paths ahead
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“This is the first evidence in mammals that preventing the decline in autophagic activity slows down cellular aging and preserves organ function.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Cross-talk between chaperone families and among the different autophagic and non-autophagic pathways has been already demonstrated in different model systems.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 5. Concluding remarks and the many open paths ahead
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“although cargo sequestration by the double membrane vesicles still takes place in the old tissues, the elimination of these vesicles by fusion with the lysosomal compartment was severely impaired (Fig. 3) (Terman, 1995)”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
- Not checked — no full text of the sourcecites Terman, 1995 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Caloric restriction and treatment with lipogenic agents are able to prevent the dysregulation of macroautophagy in old rodents, although the mechanisms by which they exert their action is still subject of investigation (Cavallini et al., 2001; Donati et al., 2004).”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 4. Proteolytic systems > 4.2. The autophagic/lysosomal system
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“this coordinated function could explain why a small improvement in one of the components of the quality control in old organisms has such dramatic beneficial effects.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 5. Concluding remarks and the many open paths ahead
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Protein quality control is essential for proper cellular function and in the orchestration of an efficient cellular response to stress.”
§ Protein Homeostasis and Aging: the importance of exquisite quality control > 5. Concluding remarks and the many open paths ahead
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
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?
The cited source says what the claim attributes to it.
In the citing paper
“Proteostasis involves mechanisms for the stabilization of correctly folded proteins, most prominently the heat-shock family of proteins, and mechanisms for the degradation of proteins by the proteasome or the lysosome (Hartl et al., 2011; Koga et al., 2011; Mizushima et al., 2008).”
From The Hallmarks of Aging (2013) · cites this paper as Koga et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“Accordingly, many studies have demonstrated that proteostasis is altered with aging (Koga et al., 2011).”
From The Hallmarks of Aging (2013) · cites this paper as Koga et al., 2011
Citations
Cites
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Self-citationSignal integration in the endoplasmic reticulum unfolded protein response
Ron, D., & Walter, P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2199 · Cited by 6,431
Autophagy regulates lipid metabolism
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009) · Nature · doi:10.1038/nature07976 · Cited by 3,975
Self-citationSuppression 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
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Regulation mechanisms and signaling pathways of autophagy
He, C., & Klionsky, D. J. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102808-114910 · Cited by 3,609
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
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865
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López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade
Chiti, F., & Dobson, C. M. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-045115 · Cited by 2,629
The amyloid state and its association with protein misfolding diseases.
Knowles, T. P. J., Vendruscolo, M., & Dobson, C. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3810 · Cited by 2,382
Genetics of longevity in model organisms: debates and paradigm shifts
Gems, D., & Partridge, L. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183712 · Cited by 499
Aging, Rejuvenation, and Epigenetic Reprogramming: Resetting the Aging Clock
Rando, T. A., & Chang, H. Y. (2012) · Cell · doi:10.1016/j.cell.2012.01.003 · Cited by 520
Molecular and physiological manifestations and measurement of aging in humans
Khan, S. S., Singer, B. D., & Vaughan, D. E. (2017) · Aging Cell · doi:10.1111/acel.12601 · Cited by 530
Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14023834 · Cited by 464
mTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 447
Energy intake and exercise as determinants of brain health and vulnerability to injury and disease
Mattson, M. P. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.012 · Cited by 434
Aging, inflammation and the environment
Bektas, A., Schurman, S. H., Sen, R., & Ferrucci, L. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.12.015 · Cited by 451
The Mitochondrial Basis of Aging and Age-Related Disorders
Srivastava, S. (2017) · Genes · doi:10.3390/genes8120398 · Cited by 446
Exercise Attenuates the Major Hallmarks of Aging
Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., Emanuele, E., Joyner, M. J., & Lucia, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2014.1623 · Cited by 413
The Biology of Aging and Cancer: A Brief Overview of Shared and Divergent Molecular Hallmarks
Aunan, J. R., Cho, W. C. S., & Søreide, K. (2017) · Aging and Disease · doi:10.14336/ad.2017.0103 · Cited by 389
Molecular and biological hallmarks of ageing
Aunan, J. R., Watson, M. M., Hagland, H. R., & Søreide, K. (2016) · British journal of surgery · doi:10.1002/bjs.10053 · Cited by 341
Integration of Clearance Mechanisms: The Proteasome and AutophagyPreprint
Wong, E. S. P., & Cuervo, A. M. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006734 · Cited by 312
Self-citationManifestations and mechanisms of stem cell aging
Liu, L. A., & Rando, T. A. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201010131 · Cited by 318
Calorie Restriction: Is AMPK a Key Sensor and Effector
Cantó, C., & Auwerx, J. (2011) · Physiology · doi:10.1152/physiol.00010.2011 · Cited by 282
Proteostasis and the Aging Proteome in Health and Disease
Morimoto, R. I., & Cuervo, A. M. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu049 · Cited by 277
Self-citationWidespread aggregation and neurodegenerative diseases are associated with supersaturated proteins
Ciryam, P., Tartaglia, G. G., Morimoto, R. I., Dobson, C. M., & Vendruscolo, M. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.09.043 · Cited by 270
Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement
Tenchov, R., Sasso, J. M., Wang, X., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00531 · Cited by 276
Aging Hallmarks: The Benefits of Physical Exercise
Rebelo-Marques, A., De Sousa Lages, A., Andrade, R., Ribeiro, C. F., Mota-Pinto, A., Carrilho, F., & Espregueira-Mendes, J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00258 · Cited by 246
Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome
Verma, R., Oania, R. S., Kolawa, N. J., & Deshaies, R. J. (2013) · eLife · doi:10.7554/elife.00308 · Cited by 253
Molecular mechanisms of renal aging
Schmitt, R., & Melk, A. (2017) · Kidney International · doi:10.1016/j.kint.2017.02.036 · Cited by 235
Dynamics of the Degradation of Ubiquitinated Proteins by Proteasomes and Autophagy
Myeku, N., & Figueiredo-Pereira, M. E. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.149252 · Cited by 203
Hexosamine Pathway Metabolites Enhance Protein Quality Control and Prolong Life
Denzel, M. S., Storm, N. J., Gutschmidt, A., Baddi, R., Hinze, Y., Jarosch, E., Sommer, T., Hoppe, T., & Antebi, A. (2014) · Cell · doi:10.1016/j.cell.2014.01.061 · Cited by 219
The role of declining adaptive homeostasis in ageing
Pomatto, L. C. D., & Davies, K. J. A. (2017) · The Journal of Physiology · doi:10.1113/jp275072 · Cited by 231
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220
Autophagy defends pancreatic β cells from human islet amyloid polypeptide-induced toxicity
Rivera, J. F., Costes, S., Gurlo, T., Glabe, C. G., & Butler, P. C. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71981 · Cited by 220
The autophagy enhancer spermidine reverses arterial aging
LaRocca, T. J., Gioscia‐Ryan, R. A., Hearon, C. M., & Seals, D. R. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.04.004 · Cited by 216
Polyamines: Functions, Metabolism, and Role in Human Disease Management
Sagar, N. A., Tarafdar, S., Agarwal, S., Tarafdar, A., & Sharma, S. (2021) · Medical Sciences · doi:10.3390/medsci9020044 · Cited by 210
Prion-like Properties of Tau Protein: The Importance of Extracellular Tau as a Therapeutic Target
Holmes, B. B., & Diamond, M. I. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.549295 · Cited by 202
Uchiki, T., Weikel, K. A., Jiao, W., Shang, F., Caceres, A., Pawlak, D., Handa, J. T., Brownlee, M., Nagaraj, R., & Taylor, A. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2011.00752.x · Cited by 200
“…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).”
BackgroundAssessing biological aging: the origin of deficit accumulation
Mitnitski, A., Song, X., & Rockwood, K. (2013) · Biogerontology · doi:10.1007/s10522-013-9446-3 · Cited by 159
Lysosome: The metabolic signaling hub
Lamming, D. W., & Bar‐Peled, L. (2019) · Traffic · doi:10.1111/tra.12617 · Cited by 173
Supersaturation is a major driving force for protein aggregation in neurodegenerative diseases
Ciryam, P., Kundra, R., Morimoto, R. I., Dobson, C. M., & Vendruscolo, M. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.12.004 · Cited by 175
Fabrizio, P., Hoon, S. S., Shamalnasab, M., Galbani, A., Wei, M., Giaever, G. N., Nislow, C., & Longo, V. D. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001024 · Cited by 176
Heat shock proteins in neurodegenerative disorders and aging
Leak, R. K. (2014) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-014-0243-9 · Cited by 175
Stress-induced biological aging: A review and guide for research priorities
Polsky, L. R., Rentscher, K. E., & Carroll, J. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.05.016 · Cited by 193
Regulation of Autophagy by Neuropathological Protein TDP-43
Bose, J. K., Huang, C.-C., & Shen, C.-K. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.237115 · Cited by 165
Vyssokikh, M. Y., Holtze, S., Averina, O. A., Lyamzaev, K. G., Panteleeva, A. A., Marey, M. V., Zinovkin, R. A., Severin, F. F., Skulachev, M. V., Fasel, N. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1916414117 · Cited by 165
Huang, X., Ke, A., Shi, G., Zhang, X., Zhang, C., Shi, Y., Wang, X., Ding, Z., Xiao, Y., Yan, J., et al. (2013) · Hepatology · doi:10.1002/hep.26255 · Cited by 164
The Expensive Germline and the Evolution of Ageing
Maklakov, A. A., & Immler, S. (2016) · Current Biology · doi:10.1016/j.cub.2016.04.012 · Cited by 159
Felszeghy, S., Viiri, J., Paterno, J. J., Hyttinen, J. M. T., Koskela, A. K. J., Chen, M., Leinonen, H., Tanila, H., Kivinen, N., Koistinen, A. P., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.09.011 · Cited by 156
Mitochondria initiate and regulate sarcopenia
Alway, S. E., Mohamed, J. S., & Myers, M. J. (2017) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000101 · Cited by 153
“FOXO proteins also regulate the UPS, which is a tightly regulated system responsible for normal intracellular protein turnover and elimination of misfolded and dysfunctional proteins (72,74).”
BackgroundAzpurua, J., Ke, Z., Chen, I. X., Zhang, Q., Ermolenko, D. N., Zhang, Z. D., Gorbunova, V. A., & Seluanov, A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313473110 · Cited by 160
Mitochondrial dysfunction in cardiac aging
Tocchi, A., Quarles, E. K., Basisty, N., Gitari, L., & Rabinovitch, P. S. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.07.009 · Cited by 154
Phenoptosis: Programmed Death of an Organism
Skulachev, M. V., & Skulachev, V. P. (2018) · Wiley eBooks · doi:10.1002/9781119432463.ch13 · Cited by 145
p62/SQSTM1 at the interface of aging, autophagy, and disease
Bitto, A., Lerner, C. A., Nacarelli, T., Crowe, E. P., Torres, C. A., & Sell, C. (2014) · AGE · doi:10.1007/s11357-014-9626-3 · Cited by 154
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Adegbuyiro, A., Sedighi, F., Pilkington, A. W., Groover, S. E., & Legleiter, J. A. (2017) · Biochemistry · doi:10.1021/acs.biochem.6b00936 · Cited by 144
Aging and longevity in the simplest animals and the quest for immortality
Petralia, R. S., Mattson, M. P., & Yao, P. J. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.05.003 · Cited by 147
Gonos, E. S., Καπετάνου, Μ., Sereikaitė, J., Bartosz, G., Naparło, K., Grzesik, M., & Sadowska‐Bartosz, I. (2018) · Aging · doi:10.18632/aging.101450 · Cited by 135
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Yu, X., Wang, Y., Krištić, J., Dong, J., Chu, X., Ge, S., Wang, H., Fang, H., Gao, Q., Liu, D., et al. (2016) · Medicine · doi:10.1097/md.0000000000004112 · Cited by 129
β-Cell Failure in Type 2 Diabetes: A Case of Asking Too Much of Too Few?
Costes, S., Langen, R., Gurlo, T., Matveyenko, A. V., & Butler, P. C. (2013) · Diabetes · doi:10.2337/db12-1326 · Cited by 129
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Zhu, Y., Ge, J., Huang, C., Liu, H., & Jiang, H. (2021) · Theranostics · doi:10.7150/thno.46436 · Cited by 126
Li, Y., Xue, Y., Xu, X., Wang, G., Liu, Y., Wu, H., Li, W., Wang, Y., Chen, Z., Zhang, W., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201798786 · Cited by 117
Maintenance of muscle mass and load‐induced growth in Muscle RING Finger 1 null mice with age
Hwee, D. T., Baehr, L. M., Philp, A., Baar, K., & Bodine, S. C. (2014) · Aging Cell · doi:10.1111/acel.12150 · Cited by 121
Immune aging in diabetes and its implications in wound healing
Moura, J., Madureira, P., Leal, E. C., Fonseca, A. C., & Carvalho, E. (2019) · Clinical Immunology · doi:10.1016/j.clim.2019.02.002 · Cited by 122
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Guerville, F., Barreto, P. D. S., Ader, I., Andrieu, S., Casteilla, L., Dray, C., Fazilleau, N., Guyonnet, S., Langin, D., Liblau, R., et al. (2020) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2019.50 · Cited by 122
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Skulachev, V. P., Holtze, S., Vyssokikh, M. Y., Bakeeva, L. E., Skulachev, M. V., Markov, A. V., Hildebrandt, T. B., & Садовничий, В. А. (2017) · Physiological Reviews · doi:10.1152/physrev.00040.2015 · Cited by 115
Sulforaphane enhances progerin clearance in H utchinson– G ilford progeria fibroblasts
Gabriel, D., Roedl, D., Gordon, L. B., & Djabali, K. (2014) · Aging Cell · doi:10.1111/acel.12300 · Cited by 114
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Uddin, M. S., Yu, W. S., & Lim, L. W. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101417 · Cited by 123
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Shacham, T., Sharma, N., & Lederkremer, G. Z. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00020 · Cited by 115
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Mechanistic links between aging and lung fibrosis
Thannickal, V. J. (2013) · Biogerontology · doi:10.1007/s10522-013-9451-6 · Cited by 109
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Stroo, E., Koopman, M., Nollen, E. A. A., & Mata‐Cabana, A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00064 · Cited by 119
Oxidative stress, aging, antioxidant supplementation and their impact on human health: An overview
Martemucci, G., Portincasa, P., Ciaula, A. D., Mariano, M., Centonze, V., & D‘Alessandro, A. G. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111707 · Cited by 112
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Carapeto, P. V., & Aguayo-Mazzucato, C. (2021) · Aging · doi:10.18632/aging.203051 · Cited by 107
“Exercise also controls age-related increases of pro-inflammatory cytokines thereby preventing accumulation of misfolded proteins [1, 116].”
BackgroundOlive Oil and the Hallmarks of Aging
Fernández-del-Río, L., Gutiérrez-Casado, E., Varela‐López, A., & Villalba, J. M. (2016) · Molecules · doi:10.3390/molecules21020163 · Cited by 100
Proteasome activation delays aging in vitro and in vivo
Chondrogianni, N., Sakellari, M., Lefaki, M., Papaevgeniou, N., & Gonos, E. S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.031 · Cited by 94
Houck, A. L., Seddighi, S., & Driver, J. A. (2018) · Current Aging Science · doi:10.2174/1874609811666180223154436 · Cited by 96
Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration
Koga, H., & Cuervo, A. M. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.07.006 · Cited by 98
Self-citationProtein homeostasis of a metastable subproteome associated with Alzheimer’s disease
Kundra, R., Ciryam, P., Morimoto, R. I., Dobson, C. M., & Vendruscolo, M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618417114 · Cited by 93
Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging
Nigro, C., Leone, A., Fiory, F., Prevenzano, I., Nicolò, A., Mirra, P., Bèguinot, F., & Miele, C. (2019) · Cells · doi:10.3390/cells8070749 · Cited by 92
The role of hydrogen sulfide in aging and age-related pathologies
Perridon, B. W., Leuvenink, H. G. D., Hillebrands, J., van Goor, H., & Bos, E. M. (2016) · Aging · doi:10.18632/aging.101026 · Cited by 90
Selective autophagy in the maintenance of cellular homeostasis in aging organisms
Hubbard, V. M., Valdor, R., Macián, F., & Cuervo, A. M. (2011) · Biogerontology · doi:10.1007/s10522-011-9331-x · Cited by 90
Self-citationCiryam, P., Kundra, R., Freer, R., Morimoto, R. I., Dobson, C. M., & Vendruscolo, M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516604113 · Cited by 85
Context-Dependent Regulation of Autophagy by IKK-NF-κB Signaling: Impact on the Aging Process
Salminen, A., Hyttinen, J. M. T., Kauppinen, A., & Kaarniranta, K. (2012) · International Journal of Cell Biology · doi:10.1155/2012/849541 · Cited by 91
CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases
Sharma, P. K., & Nag, A. (2014) · Open Biology · doi:10.1098/rsob.130217 · Cited by 88
Dang, W., Sutphin, G. L., Dorsey, J. A., Otte, G. L., Cao, K., Perry, R. M., Wanat, J. J., Saviolaki, D., Murakami, C. J., Tsuchiyama, S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.004 · Cited by 83
Anthocyanins-natural pigment of colored rice bran: Composition and biological activities
Chen, T., Xie, L., Wang, G., Jiao, J., Zhao, J., Yu, Q., Chen, Y., Shen, M., Wen, H., Ou, X., et al. (2023) · Food Research International · doi:10.1016/j.foodres.2023.113722 · Cited by 86
Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle
Fritzen, A. M., Frøsig, C., Jeppesen, J. F., Jensen, T. E., Lundsgaard, A., Serup, A. K., Schjerling, P., Proud, C. G., Richter, E. A., & Kiens, B. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.03.005 · Cited by 86
Molecular Chaperones in Parkinson's Disease – Present and Future
Ebrahimi‐Fakhari, D., Wahlster, L., & McLean, P. J. (2011) · Journal of Parkinson s Disease · doi:10.3233/jpd-2011-11044 · Cited by 83
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Gonçalves, R. S. D. S. A., Maciel, Á. C. C., Rolland, Y., Vellas, B. J., & Barreto, P. D. S. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101737 · Cited by 89
Enhancing protein disaggregation restores proteasome activity in aged cells
Andersson, V., Hanzén, S., Liu, B., Molin, M., & Nyström, T. (2013) · Aging · doi:10.18632/aging.100613 · Cited by 80
Hinault, M., Cuendet, A. F. H., Mattoo, R. U. H., Mensi, M., Dietler, G., Lashuel, H. A., & Goloubinoff, P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.127753 · Cited by 79
Cellular Protein Aggregates: Formation, Biological Effects, and Ways of Elimination
Wen, J.-H., He, X., Feng, Z.-S., Li, D.-Y., Tang, J., & Liu, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108593 · Cited by 87
E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration
Upadhyay, A., Joshi, V., Amanullah, A., Mishra, R., Arora, N., Prasad, A., & Mishra, A. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00151 · Cited by 80
Ferioli, M., Zauli, G., Maiorano, P., Milani, D., Mirandola, P., & Neri, L. M. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28304 · Cited by 85
Hypertonic stress induces rapid and widespread protein damage in C. elegans
Burkewitz, K., Choe, K. P., & Strange, K. B. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00030.2011 · Cited by 81
Key roles of autophagy in regulating T‐cell function
Botbol, Y. M., Guerrero‐Ros, I., & Macián, F. (2016) · European Journal of Immunology · doi:10.1002/eji.201545955 · Cited by 80
Evidence for the hallmarks of human aging in replicatively aging yeast
Janssens, G. E., & Veenhoff, L. M. (2016) · Microbial Cell · doi:10.15698/mic2016.07.510 · Cited by 80
The Role of Satellite Cells in Skeletal Muscle Regeneration—The Effect of Exercise and Age
Kaczmarek, A., Kaczmarek, M., Ciałowicz, M., Clemente, F. M., Wolański, P. M., Bădicu, G., & Murawska‐Ciałowicz, E. (2021) · Biology · doi:10.3390/biology10101056 · Cited by 87
Swovick, K., Firsanov, D., Welle, K. A., Hryhorenko, J. R., Wise, J. P., George, C., Sformo, T. L., Seluanov, A., Gorbunova, V., & Ghaemmaghami, S. (2021) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra120.002301 · Cited by 73
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Jeong, S., & Cho, G. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.03.136 · Cited by 75
Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses?
Abbadie, C., Pluquet, O., & Pourtier, A. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2587-9 · Cited by 77
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Takeo, S., Kawahara‐Miki, R., Goto, H., Cao, F., Kimura, K., Monji, Y., Kuwayama, T., & Iwata, H. (2013) · Molecular Reproduction and Development · doi:10.1002/mrd.22187 · Cited by 70
Metadata
- Authors
- Koga, H., Kaushik, S., & Cuervo, A. M.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Ageing research reviews
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 10
- Issue
- 2
- Pages
- 205-215
- ISSN
- 1568-1637 (ISSN-L)
- PMC
- PMC2888802
- OpenAlex
- W2166415858
- Semantic Scholar
- 31476a7ef971f336d9599bbedc73d4e0b2b52147
- Cited by
- 476
- References
- 177
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 27 · 2023: 23 · 2022: 40 · 2021: 39 · 2020: 41 · 2019: 36 · 2018: 37 · 2017: 29 · 2016: 23 · 2015: 29 · 2014: 35 · 2013: 31 · 2012: 15
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institutes of Health (5t32ag023475-24)
- National Institute on Aging (P01 AG031782, R01AG021904, R37AG021904, 5U19AG023122, TG32 AG023475, AG-021904, AG031782)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK041918, P01 DK041918)
- National Institute of Neurological Disorders and Stroke (P50 NS038370, NS038370)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- proteostasis, aging, protein quality control, molecular chaperones, proteolytic system, protein degradation, cellular stress response, protein aggregates, protein inclusions, longevity
- MeSH terms
- Aging, Autophagy, Homeostasis, Humans, Longevity, Proteins, Molecular Chaperones, Ubiquitin, Proteasome Endopeptidase Complex
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 2026-10-21, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-21 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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