Significance of the anti-aging protein Klotho

Dërmaku-Sopjani, Miribane; Kolgeci, Selim; Abazi, Sokol; Sopjani, Mentor

doi:10.3109/09687688.2013.837518

Cited by 49 publications

(36 citation statements)

References 130 publications

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“…This indicates that autophagy is crucial for maintaining the function and homeostasis of podocytes. In renal proximal tubule cells, autophagy protects against high glucose-induced cell injury [11,15,26].…”

Section: New Players: Autophagymentioning

confidence: 99%

See 1 more Smart Citation

Diabetic Nephropathy from RAAS to Autophagy: The Era for New Players

Nakhoul¹,

Nakhoul²,

Nakhoul³

2017

J Clin Exp Nephrol

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Diabetic nephropathy is a leading cause of end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality worldwide in patients with type 2 diabetes mellitus. The mechanisms behind the pathophysiology of DN are complex and continue to be not fully understood. Both metabolic (hyperglycaemia) and haemodynamic alterations interact synergistically, and have been reported to activate local RAAS resulting in increased angiotensin-2. In spite the early and chronic treatment with converting enzyme inhibitors and angiotensin receptor blocking drugs, the number of patients reaching end stage renal disease and replacement therapy are increasing.Recently different pathways were proposed to be involved in the pathogenesis of diabetic nephropathy, including the autophagy process, Klotho and the selective agonist vitamin D and his receptor. Under hyperglycemic stress especially in podocytes and proximal convolute tubule cells, there is decrease in the protective autophagic process and increase in cellular damage.α-Klotho is a multifunctional protein highly expressed in the kidney. The klotho protein has endogenous anti fibrotic function via antagonism of Wnt/β-catenin signaling, which promotes fibrogenesis, suggesting that loss of Klotho in early stage of diabetic nephropathy may contribute to the progression of DN by accelerated fibrogenesis.The selective vitamin D agonist and his receptor, play a protective pathway in diabetic nephropathy. A key renoprotective function of vitamin D is to reduce albuminuria or proteinuria, major risk factors for CKD progression, renal failure, cardiovascular events, and death. This antiproteinuric effect and the deceleration of DN progression is mediated primarily via the blocking of the renin angiotensin aldosterone system. In this review we will discuss the different new mechanisms involved in diabetic nephropathy and future therapeutic agents like the mTorc1 blocker, Rapamycin, that can upregulate the autophagy process, the new sodium-glucose transport inhibitors and Paricalcitol, the selective active vitamin D.

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Section: New Players: Autophagymentioning

confidence: 99%

“…Soluble αKlotho is released through cleavage of the extracellular domain from membrane αKlotho by secretases to function as an endocrine/paracrine substance [26][27][28][29]…”

Section: Klotho-vitamin D-vdr Axismentioning

confidence: 99%

Diabetic Nephropathy from RAAS to Autophagy: The Era for New Players

Nakhoul¹,

Nakhoul²,

Nakhoul³

2017

J Clin Exp Nephrol

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“…The best studied is Klotho, which was found to be defective in a mouse model of premature ageing that has a substantially decreased lifespan, with atherosclerosis, emphysema, osteoporosis and insulin resistance, whereas Klotho overexpression extends lifespan [130]. Klotho is a transmembrane protein that is co-receptor of fibroblast growth factor (FGF23) and regulates insulin/insulin-like growth factor signalling, phosphate homeostasis, cell survival and proliferation.…”

Section: Defective Anti-ageing Molecules and Pathwaysmentioning

confidence: 99%

Mechanisms of development of multimorbidity in the elderly

2015

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In ageing populations many patients have multiple diseases characterised by acceleration of the normal ageing process. Better understanding of the signalling pathways and cellular events involved in ageing shows that these are characteristic of many chronic degenerative diseases, such as chronic obstructive pulmonary disease (COPD), chronic cardiovascular and metabolic diseases, and neurodegeneration. Common mechanisms have now been identified in these diseases, which show evidence of cellular senescence with telomere shortening, activation of PI3K-AKT-mTOR signalling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence and low grade chronic inflammation ("inflammaging"). Many of these pathways are driven by chronic oxidative stress. There is also a reduction in anti-ageing molecules, such as sirtuins and Klotho, which further accelerates the ageing process. Understanding these molecular mechanisms has identified several novel therapeutic targets and several drugs have already been developed that may slow the ageing process, as well as lifestyle interventions, such as diet and physical activity. This indicates that in the future new treatment approaches may target the common pathways involved in multimorbidity and this area of research should be given high priority. Thus, COPD should be considered as a component of multimorbidity and common disease pathways, particularly accelerated ageing, should be targeted. @ERSpublications Multimorbidities share many common underlying mechanisms that may be linked to common causes such as oxidative stress

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“…Например, α и β-Klotho -мембранные корецепторы рецепторов факторов роста FGF, которые регулируют уровень гор-мона роста, IGF-1 и чувствительность тканей к инсу-лину (Goetz et al, 2012). При отключении гена Klotho у мышей появляются признаки ускоренного старения, такие как остеопороз, атеросклероз, эмфизема легких и повреждения почек, что ведет к ранней гибели, а при сверхэкспрессии Klotho продолжительность жизни уве-личивается (Manya et al, 2010;Dërmaku-Sopjani et al, 2013). Одним из следствий нехватки Klotho является на-рушение минерального обмена, включая гиперкальцемию, гиперфосфатемию и гипервитаминоз D (Hu et al, 2010).…”

Section: регуляция стресс-ответаunclassified

Genetics of aging and longevity

Moskalev¹,

Proshkina²,

Белый³

et al. 2016

Vestn. VOGiS

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Lifespan is a complex quantitative characteristic that makes a significant contribution to the Darwinian adaptiveness. The disclosure of the genetic structure of longevity is a fundamental problem of the evolution of ontogeny, evolutionary genetics and molecular gerontology. Under optimal conditions, the lifespan is determined by the aging rate. The aging process is made up of interrelated processes that take place at the organismal, tissue, cellular, molecular and ge ne tic levels. These include deregulation processes of homeostasis maintenance, metabolic reactions and sending intra and intercellular signals, accumulation of senescent cells, damaged organelles and mac ro molecules, epigenetic changes and genetic insta bility. The objective of this review is to summarize the available information about underlying genetic determinants of longevity and aging. Genes and signaling pathways that regulate stress response, metabolism, growth of cells and organism, maintain ing of genome and proteome integrity, qualitative and quantitative mitochondria composition, inflammatory response, apoptosis and selection of viable cells, as well as circadian rhythms were considered. The redistribution of energy resources from one pathway to the other can induce or inhibit the "longevity program", providing increased vitality and aging slowdown. Based on the analysis of geroprotective potential of examined genes' regulation, main targets have been identified to slowdown aging and achieve healthy longevity. These trends include heterochroma tin recovery, retrotransposition sup pression, aneuplo idy elimination; restoring the acidity of lysosomes; telomere elongation; suppression of chronic inflam mation; elimination of protein crosslinks; elimination of senescent cells; recovery of NAD+ levels; inhibition of mTOR, S6K, TGFβ, AT1; controlled activation of the "longevity program" genes FOXO, AMPK, PGC1α, NRF2.Key words: lifespan; aging; longevity genes; longevity program.Продолжительность жизни является комплексным количествен ным признаком, вносящим определяющий вклад в дарвиновскую приспособленность. Раскрытие генетической природы долгожи тельства -фундаментальная проблема эволюции онтогенеза, эво люционной генетики и молекулярной геронтологии. В оптималь ных условиях существования продолжительность жизни опреде ляется скоростью старения. В свою очередь, феномен старения состоит из взаимосвязанных процессов, происходящих на орга низменном, тканевом, клеточном, молекулярногенетическом уровнях. Они включают дерегуляцию процессов поддержания гомеостаза, метаболических реакций и передачи внутри и меж клеточных сигналов, накопление неспособных к делению клеток, поврежденных органелл и макромолекул, эпигенетические изме нения и генетическую нестабильность. Задачей настоящего обзора является обобщение имеющихся сведений об основных генетиче ских детерминантах продолжительности жизни и старения. Рас смотрены гены и сигнальные каскады, влияющие на скорость старения через регуляцию стрессответа, обмена веществ, роста клеток и организма, подд...

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Significance of the anti-aging protein Klotho

Cited by 49 publications

References 130 publications

Diabetic Nephropathy from RAAS to Autophagy: The Era for New Players

Diabetic Nephropathy from RAAS to Autophagy: The Era for New Players

Mechanisms of development of multimorbidity in the elderly

Genetics of aging and longevity

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