α-Klotho is unstable in human urine

Adema, Aaltje Y.; Vervloet, Marc G.; Blankenstein, Marinus A.; Heijboer, Annemieke C.; Consortium, on behalf of the NIGRAM

doi:10.1038/ki.2015.238

Cited by 23 publications

(21 citation statements)

References 6 publications

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“…Measuring α-Kl in urine was not feasible because testing urine samples for measures of α-Kl levels revealed that urinary α-Kl is not stable [ 104 – 106 ]. Furthermore, urine samples stored at − 80 °C and – 20 °C degrade when exposed to room temperature or after repeated freeze-thaw cycles [ 107 ], emphasizing that urine samples are not an alternative source for assessing α-Kl levels.…”

Section: Ethics Approval and Consent To Participatementioning

confidence: 99%

Aging and sex affect soluble alpha klotho levels in bonobos and chimpanzees

et al. 2018

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BackgroundThroughout life, physiological homeostasis is challenged and the capacity to cope with such challenges declines with increasing age. In many species, sex differences exist in life expectancy. Sex-specific differences have been related to extrinsic factors like mate competition and/or intrinsic proximate mechanisms such as hormonal changes. In humans, an intrinsic factor related to aging is soluble alpha klotho (α-Kl). Both sexes show an age-related decline in α-Kl, but throughout life women have higher levels than men of the same age. Sex differences in α-Kl have been linked to a shorter lifespan, as well as to specific morbidity factors such as atherosclerosis and arteries calcifications. In non-human animals, information on α-Kl levels is rare and restricted to experimental work. Our cross-sectional study is the first on α-Kl levels in two long-lived species: bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). As in most mammals, female bonobos and chimpanzees have longer life expectancy than males.MethodsWe measured serum α-Kl levels of 140 subjects from 16 zoos with an ELISA to examine if α-Kl levels reflect this difference in life expectancy.ResultsIn both species and in both sexes, α-Kl levels declined with age suggesting that this marker has potential for aging studies beyond humans. We also found species-specific differences. Adult female bonobos had higher α-Kl levels than males, a difference that corresponds to the pattern found in humans. In chimpanzees, we found the opposite: males had higher α-Kl levels than females.ConclusionWe suggest that contrasting sex differences in adult α-Kl levels mirror the dominance relations between females and males of the two Pan species; and that this might be related to corresponding sex differences in their exposure to stress. In humans, higher cortisol levels were found to be related to lower α-Kl levels. We conclude that there is great potential for studying aging processes in hominoids, and perhaps also in other non-human primates, by measuring α-Kl levels. To better understand the causes for sex differences in this aging marker, consideration of behavioural parameters such as competition and stress exposure will be required as well as other physiological markers.Electronic supplementary materialThe online version of this article (10.1186/s12983-018-0282-9) contains supplementary material, which is available to authorized users.

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Section: Ethics Approval and Consent To Participatementioning

confidence: 99%

Aging and sex affect soluble alpha klotho levels in bonobos and chimpanzees

et al. 2018

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“…A positive correlation between αKlotho levels (serum and urine) and eGFR has been further characterized in adult CKD patients (Akimoto et al, 2012; Hu et al, 2011; Kim et al, 2013; Kitagawa et al, 2013; Ozeki et al, 2014), although only 24-h urine αKlotho but not serum αKlotho has been shown to be independently associated with eGFR change (Akimoto et al, 2012). However, questions about the stability of αKlotho in the urine have emerged (Adema, Vervloet, Blankenstein, & Heijboer, 2015). Therefore, a standardized urine protocol is required.…”

Section: αKlotho Deficiency As a Biomarker Of Ckdmentioning

confidence: 99%

αKlotho and Chronic Kidney Disease

Neyra¹,

Hu²

2016

Vitamins &Amp; Hormones

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Alpha-Klotho (αKlotho) protein is encoded by the gene, Klotho, and functions as a coreceptor for endocrine fibroblast growth factor-23. The extracellular domain of αKlotho is cleaved by secretases and released into the circulation where it is called soluble αKlotho. Soluble αKlotho in the circulation starts to decline in chronic kidney disease (CKD) stage 2 and urinary αKlotho in even earlier CKD stage 1. Therefore soluble αKlotho is an early and sensitive marker of decline in kidney function. Preclinical data from numerous animal experiments support αKlotho deficiency as a pathogenic factor for CKD progression and extrarenal CKD complications including cardiac and vascular disease, hyperparathyroidism, and disturbed mineral metabolism. αKlotho deficiency induces cell senescence and renders cells susceptible to apoptosis induced by a variety of cellular insults including oxidative stress. αKlotho deficiency also leads to defective autophagy and angiogenesis and promotes fibrosis in the kidney and heart. Most importantly, prevention of αKlotho decline, upregulation of endogenous αKlotho production, or direct supplementation of soluble αKlotho are all associated with attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiac function and morphometry, and alleviation of vascular calcification in CKD. Therefore in rodents, αKlotho is not only a diagnostic and prognostic marker for CKD but the enhancement of endogenous or supplement of exogenous αKlotho are promising therapeutic strategies to prevent, retard, and decrease the comorbidity burden of CKD.

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“…Timing of Klotho delivery is also critical as soluble Klotho has been shown to be highly unstable in the blood and urine (169) and prevention of degradation may be essential. Numerous compounds have been approved for use in CKD but with only some positive outcomes seen suggesting the extent of reactivating and or replacing Klotho and its effects are yet to be clarified (170).…”

Section: Exercisementioning

confidence: 99%

Klotho, Aging, and the Failing Kidney

et al. 2020

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Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.

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α-Klotho is unstable in human urine

Cited by 23 publications

References 6 publications

Aging and sex affect soluble alpha klotho levels in bonobos and chimpanzees

Aging and sex affect soluble alpha klotho levels in bonobos and chimpanzees

αKlotho and Chronic Kidney Disease

Klotho, Aging, and the Failing Kidney

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