The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index; none of the 41 sources its claims cite is checked for support yet.
Human Aging and Longevity Are Characterized by High Levels of Mitokines
Open accessAbstract
Mitochondrial stress elicits the production of stress response molecules indicated as mitokines, including fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), and humanin (HN). Many diseases are characterized by progressive mitochondrial dysfunction with alterations of mitokine secretion. It is still controversial whether healthy aging and extreme longevity are accompanied by an altered production of mitokines. We analyzed FGF21, HN, and GDF15 plasma levels in 693 subjects aged from 21 to 113 years, and the association of these mitokines with parameters of health status. FGF21, HN, and GDF15 resulted increased in old age, with the highest levels found in centenarians. These molecules are associated with worsened parameters (such as handgrip strength, insulin sensitivity, triglycerides), particularly in 70-year-old persons, and their levels are inversely correlated with survival in the oldest subjects. Considering the positive biological effect of these molecules, our results can be interpreted in the framework of the hormetic paradigm as an attempt of the cells/tissues to cope with a stress that can have beneficial or detrimental effects depending on its intensity. Finally, persons with Down Syndrome (characterized by accelerated aging) have higher levels of GDF15 and HN with respect to their siblings, suggesting that these molecules, especially GDF15, could be considered markers of biological age.
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52 Own result · 29 Not checked yet · 12 Own interpretation · 7 Own method · 1 No basis given
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In the paper
“The association between cognitive status (assessed by Mini-Mental State Evaluation) and mitokines was also evaluated, and no significant association was found (data not shown).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
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In the paper
“Moreover, these are correlated with each other (Figure 1E-H).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Plasma Levels of Mitokines Increase With Age and Are Correlated With Each Other
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“GDF15 and uric acid were positively associated in YA”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“and positively with creatinine in OO”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“and with creatinine in both OO and CENT”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“GDF15 is higher in EL men (p = .001; Supplementary Figure 1B).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Plasma Levels of Mitokines Increase With Age and Are Correlated With Each Other
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In the paper
“among the 20 significant associations, half of them are found in EL group.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
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In the paper
“LL group has lower BMI”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“and negatively associated with total protein content in CENT”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Plasma FGF21 level is positively associated with BMI in EL”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 18
- It may state two separate claims as one. 21
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In the paper
“No gender differences were observed for HN (Supplementary Figure 1C).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Plasma Levels of Mitokines Increase With Age and Are Correlated With Each Other
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“FGF21, HN, and GDF15 resulted increased in old age, with the highest levels found in centenarians.”
- Also stated in: § Plasma Levels of Mitokines Increase With Age and Are Correlated With Each Other · plain
“The plasmatic levels of FGF21, HN, and GDF15 are positively and significantly correlated with age (Figure 1A-D).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Abstract
plaindirectn = 693- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Plasma Levels of Mitokines Increase With Age and Are Correlated With Each Other · 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
“FGF21 is higher in YA men (p = .016) and in OO women (p = .016; Supplementary Figure 1A)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Plasma Levels of Mitokines Increase With Age and Are Correlated With Each Other
plaincorrelational- 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
“Here, we report that the circulating levels of these mitokines increase with age.”
- Also stated in: § Conclusions · boosted
“our results show for the first time that plasma levels of three representative mitokines, FGF21, GDF15, and HN, are positively correlated with age in humans”
- Also stated in: § Discussion · plain
“The fact that the circulating levels of the three mitokines considered in this study increase with age”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
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It may state two separate claims as one.
- Also stated in: § Conclusions · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the LL group shows lower level of creatinine (p = .002)and higher insulin (p = .007)and HOMA-IR (p = .006)in comparison with the HL group (Figure 3A).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Nonagenarian Subjects and Centenarians With Lower Levels of Mitokines Have a Slight Survival Advantage
plaincorrelational- 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
“The levels of these mitokines become maximal in centenarians”
- Also stated in: § Conclusions · plain
“our results show for the first time that plasma levels of three representative mitokines, FGF21, GDF15, and HN, are positively correlated with age in humans, and become maximal in centenarians.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Conclusions · 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
“Our data indicate that the circulating levels of FGF21, GDF15, and HN are associated with worsened health parameters and with mortality in old age, and the predominant association is observed for GDF15.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Conclusions
hedgedcorrelational- 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
“GDF15 resulted the most powerful predictor of mortality among the three mitokines, being also able to improve the predictive power of mortality reported for handgrip strength.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
plaincorrelational- 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
“worsened functional and biochemical parameters (higher BMI and insulin resistance, low handgrip strength, higher CRP, triglycerides, uric acid, and creatinine) in EL and decreased survival in the oldest groups (nonagenarians and CENT).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“These data show that increased levels of mitokines (in particular, GDF15) are associated with worsening of functional and biochemical parameters (reduction of handgrip strength, HDL cholesterol, serum albumin and total proteins, and increase of BMI, HOMA-IR index, triglycerides, and uric acid), particularly in EL subjects.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > FGF21, HN, and GDF15 Plasma Levels Are Associated With Worsening of Functional and Biochemical Parameters, Particularly in EL Subjects
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
“These data are in agreement with previous literature as far as FGF21 and GDF15, which are reported to increase with age in both animal models and humans (19,20,22).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [19] Hanks, 2015, Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals, J Clin Transl Endocrinol
- Not checked yetcites [20] Tezze, 2017, Age-associated loss of OPA1 in muscle impacts muscle mass, metabolic homeostasis, systemic inflammation, and epithelial senescence, Cell Metab source
- Not checked yetcites [22] Fujita, 2016, Secreted growth differentiation factor15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders, Geriatr Gerontol Int source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A progressive mitochondrial dysfunction is known to occur with age (31)(32)(33).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Abstract
What the sources say
- Not checked yetcites [31] Lenaz, 1998, Oxidative stress, antioxidant defences and aging, Biofactors source
- Not checked yetcites [32] Short, 2005, Decline in skeletal muscle mitochondrial function with aging in humans, Proc Natl Acad Sci U S A source
- Not checked yetcites [33] Bratic, 2013, The role of mitochondria in aging, J Clin Invest source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“FGF21, GDF15, and HN concentrations were determined in plasma samples by ELISA assay using commercial kits, R&D for FGF21 (DF2100; intra-and interassay CV range: 10.2%-3.0%and 10.6%-3.1%,respectively) and GDF15 (DGD150; intra-and interassay CV range: 10.9%-1.1% and 4.1%-3.0%,respectively); CUSABIO for HN (CSB-EL015084HU; intra-and interassay CV range: 5.5%-0.7%and 11.8%-3.4%,respectively)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Data Collection
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“circulating levels of GDF15 are associated with cardiovascular diseases, insulin resistance and type 2 diabetes, neurodegeneration, and overall mortality (24,25).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Abstract
What the sources say
- Not checked yetcites [24] Adela, 2015, GDF-15 as a target and biomarker for diabetes and cardiovascular diseases: a translational prospective, J Diabetes Res source
- Not checked yetcites [25] Corre, 2013, Concise review: growth differentiation factor 15 in pathology: a clinical role, Stem Cells Transl Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The association between mitokines and parameters related to health status and phenotype (BMI, handgrip strength, glucose metabolism, lipid profile, and other biochemical markers) was evaluated by a multivariate general linear model adjusted for age, gender, and therapies in each age group.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Statistical Analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“IGF-1, which is reported to suppress HN level in plasma (38).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Plasma Levels of Mitokines Increase With Age and Are Correlated With Each Other
What the sources say
- Not checked yetcites [38] Lee, 2014, IGF-I regulates the age-dependent signaling peptide humanin, Aging Cell source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The association between clusters and mortality was evaluated by a Cox regression model adjusted for age and gender in OO and CENT.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Statistical Analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“mitochondrial dysfunction has been recently shown to be sufficient to accelerate aging process and cause premature death (20).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [20] Tezze, 2017, Age-associated loss of OPA1 in muscle impacts muscle mass, metabolic homeostasis, systemic inflammation, and epithelial senescence, Cell Metab source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“when chronically expressed, FGF21 increases with age in humans and contributes to precocious aging and premature death in mice (19,20).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Abstract
What the sources say
- Not checked yetcites [19] Hanks, 2015, Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals, J Clin Transl Endocrinol
- Not checked yetcites [20] Tezze, 2017, Age-associated loss of OPA1 in muscle impacts muscle mass, metabolic homeostasis, systemic inflammation, and epithelial senescence, Cell Metab source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the commercial antibody that we used is raised against the mitochondrial peptide of HN (http://www.uniprot.org/uniprot/Q8IVG9#sequences)and no significant cross-reactivity or interference with the analogues of HN tested so far has been observed.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“circulating levels of FGF21 are elevated in several metabolic diseases, such as type 2 diabetes (18).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Abstract
What the sources say
- Not checked yetcites [18] Liu, 2015, The role of fibroblast growth factor 21 in diabetes and its complications: a review from clinical perspective, Diabetes Res Clin Pract source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For all the samples, FGF21, GDF15, and HN were analyzed in a blind setup.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Data Collection
plain- Asserted: passes — The authors put it forward as true.
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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
“these data actually indicate that GDF15 is more affected by aging and it could be considered a potential marker of age.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
hedgedcorrelational- 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
“suggesting that these molecules, especially GDF15, could be considered markers of biological age.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Abstract
hedgedcorrelationaln = 693- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Down syndrome is characterized by segmental accelerated aging.
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
“In recent years, we and others have identified some powerful markers of biological age, such as methylation of specific CpG islands of ELOVL2 and FHL2 genes, and circulating N-glycan profiles.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“According to the concept of hormesis, whether this coping will be successful strictly depends on the intensity of the stress (47).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [47] Calabrese, 2011, Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity, Mol Aspects Med source
boostedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“HN is a neuroprotective factor that negatively regulates apoptosis, insulin resistance, and inflammation (27,29)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [27] Guo, 2003, Humanin peptide suppresses apoptosis by interfering with Bax activation, Nature source
- Not checked yetcites [29] Cobb, 2016, Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers, Aging (Albany NY) source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Accordingly, these biomarkers resulted significantly elevated in DS persons, indicating that, actually, these subjects experience an accelerated aging (48,49).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“FGF21 has cardioprotective effects (42)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [42] Cong, 2013, Proteomic study on the protective mechanism of fibroblast growth factor 21 to ischemia-reperfusion injury, Can J Physiol Pharmacol source
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.
In the paper
“GDF15 has reported cardioprotective and neuroprotective activity, and it can affect mitochondrial biogenesis and fatty acid metabolism (22).”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [22] Fujita, 2016, Secreted growth differentiation factor15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders, Geriatr Gerontol Int source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
In the paper
“positive metabolic effects, including weight loss, improved glycemia, and decreased inflammation (43)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [43] Fisher, 2016, Understanding the physiology of FGF21, Annu Rev Physiol source
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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“circulating levels of GDF15 have been found associated with cardiovascular diseases, insulin resistance and type 2 diabetes, neurodegeneration and overall mortality [reviewed in Fujita and coworkers (22)].”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [22] Fujita, 2016, Secreted growth differentiation factor15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders, Geriatr Gerontol Int source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
In the paper
“it delays immunosenescence (44)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [44] Youm, 2016, Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution, Proc Natl Acad Sci U S A source
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.
In the paper
“increases the life span of animals in experimental models (16)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [16] Salminen, 2017, Regulation of longevity by FGF21: interaction between energy metabolism and stress responses, Ageing Res Rev source
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
“Rather, they may represent the attempt of the cell/tissue to cope with an ongoing stress.”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“it plays a protective role in many pathologies such as Alzheimer's disease, cardiovascular diseases, type 2 diabetes, inflammation, as reviewed by Gong and coworkers (45)”
§ Human Aging and Longevity Are Characterized by High Levels of Mitokines > Discussion
What the sources say
- Not checked yetcites [45] Gong, 2014, Humanin and age-related diseases: a new link, Front Endocrinol (Lausanne) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
Down syndrome is characterized by segmental accelerated aging.
“a condition characterized by segmental accelerated aging”
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
“Since FGF21 effects are dose dependent, a moderate induction results in adaptive responses to stress, while a dramatic increase is detrimental [218].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [218]
In the citing paper
“Since mitochondrial dysfunction triggers the expression in muscle of FGF21 and GDF15, which positively correlate with unhealthy aging and mortality [6,28], we measured the transcript levels of these hormones in DKO muscles.”
From Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles (2019) · cites this paper as [28]
In the citing paper
“Moreover, in humans, Fgf21 levels are inversely correlated with survival [28].”
From Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles (2019) · cites this paper as [28]
In the citing paper
“Interestingly, mild mitochondrial stress might elicit beneficial effects on health and lifespan through the activation of mitochondrial hormesis [28,36].”
From Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles (2019) · cites this paper as [28]
In the citing paper
“The discrepancy in the two observations can most likely be explained by the threshold effect of Fgf21, where moderate levels result in adaptive responses to stress, while exacerbated levels are detrimental to stress [28].”
From Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles (2019) · cites this paper as [28]
Citations
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · cited 1×
“Insulin resistance status was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), according to the previously described formula (35): insulin (in microunits per milliliter) × glucose (in millimoles per liter)/22.”
MethodAging: 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
The mitochondrial basis of aging
Sun, N., Youle, R. J., & Finkel, T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.028 · Cited by 1,441
Decline in skeletal muscle mitochondrial function with aging in humans
Short, K. R., Bigelow, M. L., Kahl, J., Singh, R., Coenen-Schimke, J., Raghavakaimal, S., & Nair, K. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501559102 · Cited by 1,333
Rates of Behavior and Aging Specified by Mitochondrial Function During Development
Dillin, A., Hsu, A.-L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Science · doi:10.1126/science.1077780 · Cited by 1,121
The role of mitochondria in aging
Bratic, A., & Larsson, N.-G. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64125 · Cited by 1,087
The Cell Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity
Durieux, J., Wolff, S., & Dillin, A. (2011) · Cell · doi:10.1016/j.cell.2010.12.016 · Cited by 1,059 · cited 3×
“Dillin and coworkers hypothesized some years ago that a mitochondrial stress could elicit beneficial effects on health and life span spreading at organismal level through soluble elements putatively indicated as mitokines (7), and many data indicate indeed that a mild mitochondrial dysfunction actually promotes longev…”
BackgroundA systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature Genetics · doi:10.1038/ng1056 · Cited by 969
Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912
Kim, K. H., Jeong, Y. T., Oh, H., Kim, S. H., Cho, J. M., Kim, Y.-N., Kim, S. S., Kim, D. H., Hur, K. Y., Kim, H. K., et al. (2013) · Nature Medicine · doi:10.1038/nm.3014 · Cited by 774
Cited by
Sorted by citations
Items 201–217 of 217
Alvarez, J.-A., Medford, A., Strozza, C., Thinggaard, M., & Christensen, K. (2021) · Figshare · doi:10.6084/m9.figshare.14897300
Alvarez, J.-A., Medford, A., Strozza, C., Thinggaard, M., & Christensen, K. (2021) · Figshare · doi:10.6084/m9.figshare.14897339
Alvarez, J.-A., Medford, A., Strozza, C., Thinggaard, M., & Christensen, K. (2021) · Figshare · doi:10.6084/m9.figshare.14897312
Alvarez, J.-A., Medford, A., Strozza, C., Thinggaard, M., & Christensen, K. (2021) · Figshare · doi:10.6084/m9.figshare.14897336
Luther, J., Carreau, A., Baldauf, C., Neven, M., Koehne, T., Amling, M., & Schinke, T. (2026) · Cancer & Metabolism · doi:10.1186/s40170-025-00417-y
Implication de GDF15 dans la sénescence et les fonctions des cellules endothéliales.
Ha, G. (2019) · theses.fr (ABES) · doi:10.70675/da2fe5b4z744dz47f9z8aadza1047172fb7c
de Vos, C., Mergl, R., Biemann, R., Baber, R., Riedel-Heller, S., Wirkner, K., Kluge, M., & Wittekind, D. A. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121832
Liao, Y., Xu, J., Jiao, Y., Sun, X., Gao, M., Ding, Y., Cai, D., Shen, Y., Zhou, X., & Han, W. (2026) · Biomedicines · doi:10.3390/biomedicines14051048
Zhang, G., Ren, D., & Wang, S. (2026) · Hearing Research · doi:10.1016/j.heares.2026.109679
Progress in research on cognitive frailty in the older adults: a narrative review
Shao, S., Zhao, B., Jin, S., & Sha, L. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1791816
Shiohama, A., Sasaki, T., Abe, Y., Shikimoto, R., & Arai, Y. (2026) · GeroScience · doi:10.1007/s11357-026-02355-z
Humanin Mitigates Aβ‐Induced Retinal Pigment Epithelium Injury via AMPK ‐Beclin1‐Dependent Mitophagy
Jang, H. D., Choi, S., Kim, S., Kim, S., Jo, D. H., Lee, T. G., Park, K., & Kim, J. H. (2026) · Aging Cell · doi:10.1111/acel.70601
Medeiros, E. B., Monteiro, I. D. O., Kluwe‐Schiavon, B., Possamai, O. L., Fenilli, G. P., Keller, G. S., Lídio, A. V., Casagrande, D. D., Souza, C. S. M., Silveira, G. D. B., et al. (2026) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-026-11104-9
Drapkina, O. M., & Timofeev, Y. S. (2026) · CARDIOVASCULAR THERAPY AND PREVENTION · doi:10.15829/1728-8800-2026-4856
Biological functions and emerging interplay of FGF21 and GDF15 in metabolic diseases and aging
Salmón‐Gómez, L., Keipert, S., Catalán, V., Rodrı́guez, A., Becerril, S., Frühbeck, G., & Gómez‐Ambrosi, J. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00627-w
Metadata
- Authors
- Conte, M., Ostan, R., Fabbri, C., Santoro, A., Guidarelli, G., Vitale, G., Mari, D., Sevini, F., Capri, M., Sandri, M., Monti, D., Franceschi, C., & Salvioli, S.
- Affiliations
- University of Bologna (IT)
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Cusano Milanino
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- University of Padua (IT)
- University of Florence (IT)
- IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy
- Corresponding author
- Conte, Maria
- ORCID
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-06-27
- Volume
- 74
- Issue
- 5
- Pages
- 600-607
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- OpenAlex
- W2810573409
- Semantic Scholar
- 0ec1a949c64991e669493252e26a4d676f0b4431
- Cited by
- 219
- References
- 51
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 25 · 2023: 20 · 2022: 26 · 2021: 52 · 2020: 36 · 2019: 11 · 2018: 5
- FWCI
- 22.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, other-oa)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Roberto and Cornelia Pallotti's Legacy for Cancer Research (634821)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › GDF15 and Related Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitokines, human aging, longevity, centenarians, FGF21, GDF15, humanin, mitochondrial stress, mitochondrial dysfunction, hormesis, biological age, Down syndrome, accelerated aging, grip strength, insulin sensitivity, triglycerides, survival
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Down Syndrome, Female, Fibroblast Growth Factors, Humans, Longevity, Male, Middle Aged, Mitochondria, Surveys and Questionnaires, Biomarkers, Intracellular Signaling Peptides and Proteins, Growth Differentiation Factor 15, Unfolded Protein Response
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 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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