Improving Brain Creatine Uptake by Klotho Protein Stimulation: Can Diet Hit the Big Time?

Ostojić, Sergej M.; Engeset, Dagrun

doi:10.3389/fnut.2021.795599

Cited by 3 publications

(2 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have found that whole-diet interventions are effective in increasing klotho function. A low-calorie, high-protein diet increases klotho levels in a rat's brain, while a phosphate-restricted diet improves klotho kidney expression in a mouse model of polycystic kidney disease [45]. In a cross-sectional cohort analysis of 8456 participants (NHANES), klotho plasma levels were compared to the Healthy Eating Index-2015 (HEI) in middleto-older aged (40-79 years old) adults [46].…”

Section: Nutritionmentioning

confidence: 99%

The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements

Paquette,

Rhéaume,

Cordeau

et al. 2023

Metabolites

View full text Add to dashboard Cite

Aging is not a disease; it is a natural evolution of human physiology. Medical advances have extended our life expectancy, but chronic diseases and geriatric syndrome continue to affect the increasingly aging population. Yet modern medicine perpetuates an approach based on treatment rather than prevention and education. In order to help solve this ever-growing problem, a new discipline has emerged: lifestyle medicine. Nutrition, physical activity, stress management, restorative sleep, social connection, and avoidance of risky substances are the pillars on which lifestyle medicine is founded. The aim of this discipline is to increase healthspan and reduce the duration of morbidity by making changes to our lifestyle. In this review, we propose the use of klotho protein as a novel biomarker for lifestyle medicine in order to quantify and monitor the health status of individuals, as no integrative tool currently exists.

show abstract

Section: Nutritionmentioning

confidence: 99%

The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements

Paquette,

Rhéaume,

Cordeau

et al. 2023

Metabolites

View full text Add to dashboard Cite

show abstract

“…Gene therapy: Arbel Rubinstein et al, 2021 ; Franco et al, 2021 ; Lin & Sun, 2015a , b ; Ni et al, 2021 ; Mencke et al, 2017 ; Shin et al, 2019 ; Xiang et al, 2021 ; Zeng et al, 2019 . Traditional medicines, nutraceuticals and supplements: Dehghani et al, 2019 ; Feng and Huang, 2022 ; Hsu et al, 2014 ; Kamel et al, 2022 ; Long et al, 2018 ; Li SS, et al, 2018 ; Lim SW, et al, 2019 ; Long et al, 2018 ; Ostojic and Engeset, 2021 ; Zhang P, et al, 2016 ; Zhang XT, et al, 2020 ; Zhou et al, 2015 . Exercise and sports: Amaro-Gahete et al, 2018 , 2019a , b ; Morishima and Ochi, 2021 ; Tan et al, 2018 .…”

Section: Approaches To Klotho-based Therapymentioning

confidence: 99%

Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations

Prud’homme

Kurt²,

Wang

2022

Front. Aging

View full text Add to dashboard Cite

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.

show abstract