References Values of Soluble α-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18–85 Years

Espuch-Oliver, Andrea; Vázquez-Lorente, Héctor; Jurado‐Fasoli, Lucas; Haro-Muñoz, Tomás de; Díaz-Alberola, Irene; López-Velez, María del Señor; Haro-Romero, Teresa de; Castillo, Manuel J.; Amaro-Gahete, Francisco J.

doi:10.3390/jcm11092415

Cited by 21 publications

(18 citation statements)

References 38 publications

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“…Several available sKlotho assays failed to precisely determine the actual sKlotho level or the range of the sKlotho reference value ( Heijboer et al, 2013 ; Neyra et al, 2020b ). Interestingly, a recent study by Espuch-Oliver et al (2022) investigated the reference values of serum sKlotho in a larger sample with 346 healthy adults by ELISA. They observed that sKlotho levels differed significantly across ages, and sKlotho was inversely correlated with age in healthy subjects.…”

Section: How To Resolve the Controversymentioning

confidence: 99%

The controversy of klotho as a potential biomarker in chronic kidney disease

Liu

Sha

et al. 2022

Front. Pharmacol.

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Klotho is an identified longevity gene with beneficial pleiotropic effects on the kidney. Evidence shows that a decline in serum Klotho level occurs in early chronic kidney disease (CKD) and continues as CKD progresses. Klotho deficiency is associated with poor clinical outcomes and CKD mineral bone disorders (CKD-MBD). Klotho has been postulated as a candidate biomarker in the evaluation of CKD. However, the evidence for the clinical significance of the relationship between Klotho and kidney function, CKD stage, adverse kidney and/or non-kidney outcomes, and CKD-MBD remains inconsistent and in some areas, contradictory. Therefore, there is uncertainty as to whether Klotho is a potential biomarker in CKD; a general consensus regarding the clinical significance of Klotho in CKD has not been reached, and there is limited evidence synthesis in this area. To address this, we have systematically assessed the areas of controversy, focusing on the inconsistencies in the evidence base. We used a PICOM strategy to search for relevant studies and the Newcastle–Ottawa Scale scoring to evaluate included publications. We reviewed the inconsistent clinical findings based on the relationship of Klotho with CKD stage, kidney and/or non-kidney adverse outcomes, and CKD-MBD in human studies. Subsequently, we assessed the underlying sources of the controversies and highlighted future directions to resolve these inconsistencies and clarify whether Klotho has a role as a biomarker in clinical practice in CKD.

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Section: How To Resolve the Controversymentioning

confidence: 99%

The controversy of klotho as a potential biomarker in chronic kidney disease

Liu

Sha

et al. 2022

Front. Pharmacol.

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“…In humans, serum levels of Klotho were also decreased with age [ 19 , 20 ]. Espuch-Oliver et al demonstrated that soluble levels of Klotho were decreased in healthy-aged individuals duo to aging-related physiological declines [ 21 ]. They proposed that the soluble Klotho (S-Klotho) level through ELISA measurement could be considered a simple and meaningful marker of aging that can improve quality of life for the elderly [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Espuch-Oliver et al demonstrated that soluble levels of Klotho were decreased in healthy-aged individuals duo to aging-related physiological declines [ 21 ]. They proposed that the soluble Klotho (S-Klotho) level through ELISA measurement could be considered a simple and meaningful marker of aging that can improve quality of life for the elderly [ 21 ]. Actually, the Klotho gene encoded several forms of Klotho protein, including membrane bound form and secreted form Klotho [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Composite Dietary Antioxidant Index and Plasma Levels of Soluble Klotho: Insights from NHANES

Chen

Miao

et al. 2023

Oxidative Medicine and Cellular Longevity

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Objectives. The association between dietary antioxidants and soluble Klotho (S-Klotho) levels remains unknown. We investigated to explore whether the composite dietary antioxidant index (CDAI) was associated with serum levels of S-Klotho in the middle-aged population. Methods. Eligible participants were identified from the National Health and Nutrition Examination Surveys (NHANES) from 2007 until 2016. The CDAI was calculated from the intake of six dietary antioxidants. The serum levels of S-Klotho were measured via enzyme-linked immunosorbent assay (ELISA). Generalized linear and nonlinear models were established to analyze the relationship between CDAI and S-Klotho levels. Results. Based on the S-Klotho quartiles, S-Klotho levels were higher in young women, Blacks, higher education, never smokers, lower waistlines, no medication use, and those with higher CDAI. Univariate analysis revealed that age, gender, race, smoking status, body mass index, waistline, and medication use were associated with serum levels of S-Klotho. When potential confounders were controlled, CDAI was significantly associated with S-Klotho levels. Subgroup analysis also revealed that this association remained significant in individuals who had the highest quartiles of CDAI, aged population (>60 years), male, and never smoker. A nonlinear relationship was observed between the CDAI and S-Klotho plasma concentrations. Conclusion. CDAI was positively correlated with plasma levels of S-Klotho after controlling for covariates. Further studies are needed to validate the current findings and explore the fundamental mechanisms.

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“…Klotho expression declines with age, renal failure, diabetes and neurodegenerative disease. The age-related decline in serum levels appears to be similar in men and women; and reference values have recently been reported (Espuch-Oliver et al, 2022). Notably, a recent study of American adults showed that low serum Klotho levels correlate with an increased all-cause death rate (Kresovich and Bulka, 2021).…”

Section: Introductionmentioning

confidence: 81%

“…Another relevant observation is the wide variability in Klotho levels between individuals. For instance, in a 18–35 age group approximately half of individuals had low levels, comparable to aged subjects, whereas the other half had high levels ( Espuch-Oliver et al, 2022 ). In the 55–85 age group, however, levels were more consistently low.…”

Section: Klotho and Neurodegenerative Diseasesmentioning

confidence: 99%

Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations

Prud’homme

Kurt²,

Wang

2022

Front. Aging

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The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan. In humans, Klotho levels decline with age, chronic kidney disease, diabetes, Alzheimer’s disease and other conditions. Low Klotho levels correlate with an increase in the death rate from all causes. Klotho acts either as an obligate coreceptor for fibroblast growth factor 23 (FGF23), or as a soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced in the kidneys, but also in the brain, pancreas and other tissues. On renal tubular-cell membranes, it associates with FGF receptors to bind FGF23. Produced in bones, FGF23 regulates renal excretion of phosphate (phosphaturic effect) and vitamin D metabolism. Lack of Klotho or FGF23 results in hyperphosphatemia and hypervitaminosis D. With age, human renal function often deteriorates, lowering Klotho levels. This appears to promote age-related pathology. Remarkably, Klotho inhibits four pathways that have been linked to aging in various ways: Transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), Wnt and NF-κB. These can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis and neoplasia. Furthermore, Klotho increases cell-protective antioxidant enzymes through Nrf2 and FoxO. In accord, preclinical Klotho therapy ameliorated renal, cardiovascular, diabetes-related and neurodegenerative diseases, as well as cancer. s-Klotho protein injection was effective, but requires further investigation. Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In clinical trials, increased Klotho was noted with renin-angiotensin system inhibitors (losartan, valsartan), a statin (fluvastatin), mTOR inhibitors (rapamycin, everolimus), vitamin D and pentoxifylline. In preclinical work, antidiabetic drugs (metformin, GLP-1-based, GABA, PPAR-γ agonists) also enhanced Klotho. Several traditional medicines and/or nutraceuticals increased Klotho in rodents, including astaxanthin, curcumin, ginseng, ligustilide and resveratrol. Notably, exercise and sport activity increased Klotho. This review addresses molecular, physiological and therapeutic aspects of Klotho.

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References Values of Soluble α-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18–85 Years

Cited by 21 publications

References 38 publications

The controversy of klotho as a potential biomarker in chronic kidney disease

The controversy of klotho as a potential biomarker in chronic kidney disease

Composite Dietary Antioxidant Index and Plasma Levels of Soluble Klotho: Insights from NHANES

Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations

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