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Chronic kidney disease and premature ageing - Nature Reviews Nephrology

  • ️Stenvinkel, Peter
  • ️Tue Oct 07 2014
  • Carrero, J. J. et al. Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients. J. Intern. Med. 263, 302–312 (2008).

    CAS  PubMed  Google Scholar 

  • Kooman, J. P. et al. Out of control: accelerated aging in uremia. Nephrol. Dial. Transplant. 28, 48–54 (2013).

    PubMed  Google Scholar 

  • Stenvinkel, P. & Larsson, T. Chronic kidney disease: a clinical model of premature aging. Am. J. Kidney. Dis. 62, 339–351 (2013).

    PubMed  Google Scholar 

  • Amann, K. & Ritz, E. Cardiovascular abnormalities in ageing and in uraemia—only analogy or shared pathomechanisms? Nephrol. Dial. Transplant. 13 (Suppl. 7), 6–11 (1998).

    PubMed  Google Scholar 

  • Langen, R. C. et al. Triggers and mechanisms of skeletal muscle wasting in chronic obstructive pulmonary disease. Int. J. Biochem. Cell. Biol. 45, 2245–2256 (2013).

    CAS  PubMed  Google Scholar 

  • von Haehling, S. et al. Muscle wasting in heart failure: an overview. Int. J. Biochem. Cell. Biol. 45, 2257–2265 (2013).

    CAS  PubMed  Google Scholar 

  • Pathai, S. et al. Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study. AIDS 27, 2375–2378 (2013).

    PubMed  Google Scholar 

  • Crowson, C. S. et al. Could accelerated aging explain the excess mortality in patients with seropositive rheumatoid arthritis? Arthritis Rheum. 62, 378–382 (2010).

    PubMed  PubMed Central  Google Scholar 

  • Karatsoreos, I. N. & McEwen, B. S. Resilience and vulnerability: a neurobiological perspective. F1000 Prime Rep. 5, 13 (2013).

    Google Scholar 

  • Parrella, E. & Longo, V. D. Insulin/IGF-I and related signaling pathways regulate aging in nondividing cells: from yeast to the mammalian brain. Scientific World Journal 10, 161–177 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eijkelenboom, A. & Burgering, B. M. FOXOs: signaling integrators for homeostasis maintenance. Nat. Rev. Mol. Cell. Biol. 14, 83–97 (2013).

    CAS  PubMed  Google Scholar 

  • Kirkwood, T. B. Understanding ageing from an evolutionary perspective. J. Intern. Med. 2008 263, 117–127 (2008).

    CAS  Google Scholar 

  • Briet, M. et al. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int. 82, 388–400 (2012).

    PubMed  Google Scholar 

  • Carracedo, J. et al. Cellular senescence determines endothelial cell damage induced by uremia. Exp. Gerontol. 48, 766–773 (2013).

    CAS  PubMed  Google Scholar 

  • Ito, K. et al. Geroprotectors as a novel therapeutic strategy for COPD, an accelerating aging disease. Int. J. Chron. Obstruct. Pulmon. Dis. 7, 641–652 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Georgin-Lavialle, S. et al. The telomere/telomerase system in autoimmune and systemic immune-mediated diseases. Autoimmun. Rev. 9, 646–651 (2010).

    CAS  PubMed  Google Scholar 

  • Shiels, P. G. Improving precision in investigating aging: why telomeres can cause problems. J. Gerontol. 65, 789–791 (2010).

    Google Scholar 

  • Gingell-Littlejohn, M. et al. Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria. PLoS ONE 8, e68133 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Acquaah-Mensah, G. K. et al. Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease. PLoS Comput. Biol. 8, e1002597 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baker, G. T. 3rd & Sprott, R. L. Biomarkers of aging. Exp. Gerontol. 23, 223–239 (1988).

    PubMed  Google Scholar 

  • Der, G. et al. Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland? PLoS ONE 7, e45166 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gabai, V. L. et al. HSP72 depletion suppresses γH2AX activation by genotoxic stresses via p53/p21 signaling. Oncogene 29, 1952–1962 (2010).

    CAS  PubMed  Google Scholar 

  • Goldman, R. D. et al. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc. Natl Acad. Sci. USA 101, 8963–8968 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Himmelfarb, J. et al. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 62, 1524–1538 (2002).

    CAS  PubMed  Google Scholar 

  • Ghoorah, K. et al. Increased cardiovascular risk in patients with chronic obstructive pulmonary disease and the potential mechanisms linking the two conditions: a review. Cardiol. Rev. 21, 196–202 (2013).

    PubMed  Google Scholar 

  • Lewis, W. Atherosclerosis in AIDS: potential pathogenetic roles of antiretroviral therapy and HIV. J. Mol. Cell. Cardiol. 32, 2115–2129 (2000).

    CAS  PubMed  Google Scholar 

  • van Breukelen-van der Stoep, D. F. et al. Cardiovascular risk in rheumatoid arthritis: how to lower the risk? Atherosclerosis 231, 163–172 (2013).

    CAS  PubMed  Google Scholar 

  • Gómez, L. A. & Hagen, T. M. Age-related decline in mitochondrial bioenergetics: does supercomplex destabilization determine lower oxidative capacity and higher superoxide production? Semin. Cell Dev. Biol. 23, 758–767 (2012).

    PubMed  Google Scholar 

  • Sukhanov, S. et al. Angiotensin II, oxidative stress and skeletal muscle wasting. Am. J. Med. Sci. 342, 143–147 (2011).

    PubMed  PubMed Central  Google Scholar 

  • Hybertson, B. M. et al. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol. Aspects Med. 32, 234–246 (2011).

    CAS  PubMed  Google Scholar 

  • Grimes, K. M. et al. And the beat goes on: maintained cardiovascular function during aging in the longest-lived rodent, the naked mole-rat. Am. J. Physiol. Heart. Circ. Physiol. 307, H289–H291 (2014).

    Google Scholar 

  • De Waal, E. M. et al. Elevated protein carbonylation and oxidative stress do not affect protein structure and function in the long-living naked-mole rat: a proteomic approach. Biochem. Biophys. Res. Commun. 434, 815–819 (2013).

    CAS  PubMed  Google Scholar 

  • Sosnowska, D. et al. A heart that beats for 500 years: age-related changes in cardiac proteasome activity, oxidative protein damage and expression of heat shock proteins, inflammatory factors, and mitochondrial complexes in Arctica islandica, the longest-living noncolonial animal. J. Gerontol. A Biol. Sci. Med. Sci. http://dx.doi.org/10.1093/gerona/glt201.

  • Stevenson, K. S. et al. Breath ethane peaks during a single haemodialysis session and is associated with time on dialysis. J. Breath. Res. 2, 02600 (2008).

    Google Scholar 

  • Mutsaers, H. A. et al. Uremic toxins inhibit renal metabolic capacity through interference with glucuronidation and mitochondrial respiration. Biochim. Biophys. Acta. 1832, 142–150 (2013).

    CAS  PubMed  Google Scholar 

  • Barnes, P. J. New anti-inflammatory targets for chronic obstructive pulmonary disease. Nat. Rev. Drug Discov. 12, 543–559 (2013).

    PubMed  Google Scholar 

  • Couillard, A. & Prefaut, C. From muscle disuse to myopathy in COPD: potential contribution of oxidative stress. Eur. Resp. J. 26, 703–719 (2005).

    CAS  Google Scholar 

  • Rubattu, S. et al. Pathogenesis of chronic cardiorenal syndrome: is there a role for oxidative stress? Int. J. Mol. Sci. 14, 23011–23032 (2013).

    PubMed  PubMed Central  Google Scholar 

  • Ye, Y. et al. Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. PLoS ONE 8, e56803 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coombes, J. S. & Fassett, R. G. Antioxidant therapy in hemodialysis patients: a systematic review. Kidney Int. 81, 233–246 (2012).

    CAS  PubMed  Google Scholar 

  • Tsakiri, E. N. et al. Proteasome dysfunction in Drosophila signals to an Nrf2-dependent regulatory circuit aiming to restore proteostasis and prevent premature aging. Aging Cell 12, 802–813 (2013).

    CAS  PubMed  Google Scholar 

  • Kim, E. B. et al. Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 479, 223–227 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, H. J. & Vaziri, N. D. Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am. J. Physiol. Renal Physiol. 298, F662–F671 (2010).

    CAS  PubMed  Google Scholar 

  • Zhang, H. S. et al. Nrf2 is involved in inhibiting Tat-induced HIV-1 long terminal repeat transactivation. Free Radic. Biol. Med. 47, 261–268 (2009).

    CAS  PubMed  Google Scholar 

  • de Zeeuw, D. et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N. Engl. J. Med. 369, 2492–2503 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Aminzadeh, M. A. et al. Role of impaired Nrf2 activation in the pathogenesis of oxidative stress and inflammation in chronic tubulo-interstitial nephropathy. Nephrol. Dial. Transplant. 28, 2038–2045 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cochemé, H. M. et al. Measurement of H2O2 within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix. Cell. Metab. 13, 340–350 (2011).

    PubMed  PubMed Central  Google Scholar 

  • Licastro, F. et al. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun. Ageing 2, 8 (2005).

    PubMed  PubMed Central  Google Scholar 

  • Kato, S. et al. Aspects of immune dysfunction in end-stage renal disease. Clin. J. Am. Soc. Nephrol. 3, 1526–1533 (2008).

    PubMed  PubMed Central  Google Scholar 

  • von Haehling, S. et al. Inflammatory biomarkers in heart failure revisited: much more than innocent bystanders. Heart Fail. Clin. 5, 549–560 (2009).

    PubMed  Google Scholar 

  • Jurk, D. et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat. Commun. 2, 4172 (2014).

    PubMed  Google Scholar 

  • Campis, J. et al. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell. Biol. 8, 729–740 (2007).

    Google Scholar 

  • Shiels, P. G. et al. Accelerated telomere attrition is associated with relative household income, diet and inflammation in the pSoBid cohort. PLoS ONE 6, e22521 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Betjes, M. G. et al. Loss of renal function causes premature aging of the immune system. Blood Purif. 36, 173–178 (2013).

    PubMed  Google Scholar 

  • Meuwese, C. L. et al. Recent insights in inflammation-associated wasting in patients with chronic kidney disease. Contrib. Nephrol. 171, 120–126 (2011).

    CAS  PubMed  Google Scholar 

  • Shanahan, C. M. Mechanisms of vascular calcification in CKD—evidence for premature ageing? Nat. Rev. Nephrol. 9, 661–670 (2013).

    CAS  PubMed  Google Scholar 

  • Matsuoka, S. et al. The relationship between small pulmonary vascular alteration and aortic atherosclerosis in chronic obstructive pulmonary disease: quantitative CT analysis. Acad. Radiol. 18, 40–46 (2011).

    PubMed  Google Scholar 

  • Paccou, J. et al. Vascular calcification in rheumatoid arthritis: prevalence, pathophysiological aspects and potential targets. Atherosclerosis 224, 283–290 (2012).

    CAS  PubMed  Google Scholar 

  • Carrero, J. J. & Stenvinkel, P. Inflammation in end-stage renal disease-what have we learned in 10 years? Semin. Dial. 23, 498–509 (2010).

    PubMed  Google Scholar 

  • McGuinness, D. et al. Socio-economic status is associated with epigenetic differences in the pSoBid cohort. Int. J. Epidemiol. 41, 151–160 (2012).

    PubMed  Google Scholar 

  • Salminen, A. et al. Activation of innate immunity system during aging: NF-κB signaling is the molecular culprit of inflamm-aging. Ageing Res. Rev. 7, 83–105 (2008).

    CAS  PubMed  Google Scholar 

  • Mendelsohn, A. R. & Larrick, J. W. Dietary modification of the microbiome affects risk for cardiovascular disease. Rejuvenation Res. 16, 241–244 (2013).

    CAS  PubMed  Google Scholar 

  • Cabreiro, F. et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228–239 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stenvinkel, P. & Johnson, R. J. Kidney biomimicry—a rediscovered scientific field that could provide hope to patients with kidney disease. Arch. Med. Res. 44, 584–590 (2013).

    PubMed  Google Scholar 

  • Kooman, J. P. et al. 'Time and time again': oscillatory and longitudinal time patterns in dialysis patients. Kidney Blood Press. Res. 35, 534–548 (2012).

    PubMed  Google Scholar 

  • Russcher, M., et al. Long-term effects of melatonin on quality of life and sleep in hemodialysis patients (Melody study): a randomized controlled trial. Br. J. Clin. Pharmacol. 76, 668–679 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Parish, J. M. Sleep-related problems in common medical conditions. Chest 135, 563–572 (2009).

    PubMed  Google Scholar 

  • Vink, E. E. et al. Sympathetic hyperactivity in chronic kidney disease: pathophysiology and (new) treatment options. Curr. Hypertens. Rep. 15, 95–101 (2013).

    CAS  PubMed  Google Scholar 

  • van Gestel, A. J. et al. Sympathetic overactivity and cardiovascular disease in patients with chronic obstructive pulmonary disease (COPD). Discov. Med. 14, 359–368 (2012).

    PubMed  Google Scholar 

  • Lymperopoulos, A. et al. Adrenergic nervous system in heart failure: pathophysiology and therapy. Circ. Res. 113, 739–753 (2013).

    CAS  PubMed  Google Scholar 

  • van Gurp, P. J. et al. Sympathetic nervous system function in HIV-associated adipose redistribution syndrome. AIDS 20, 773–775 (2006).

    PubMed  Google Scholar 

  • Evrengül, H. et al. Heart rate variability in patients with rheumatoid arthritis. Rheumatol. Int. 24, 198–202 (2004).

    PubMed  Google Scholar 

  • Seals, D. R. et al. The aging cardiovascular system: changes in autonomic function at rest and in response to exercise. Int. J. Sport. Nutr. Exerc. Metab. 11, S189–S195 (2011).

    Google Scholar 

  • Kooman, J. P. et al. Blood pressure during the interdialytic period in haemodialysis patients: estimation of representative blood pressure values. Nephrol. Dial. Transplant. 7, 917–923 (1992).

    CAS  PubMed  Google Scholar 

  • Schillaci, G. et al. Symmetric ambulatory arterial stiffness index and 24-h pulse pressure in HIV infection: results of a nationwide cross-sectional study. J. Hypertens. 31, 560–567 (2013).

    CAS  PubMed  Google Scholar 

  • Kario, K. et al. Sleep-predominant lowering of ambulatory blood pressure by bedtime inhalation of a novel muscarinic M3 receptor antagonist: a new “bronchoantihypertensive” strategy targeting the lung in hypertension with chronic obstructive pulmonary disease. Hypertens. Res. 31, 817–821 (2008).

    CAS  PubMed  Google Scholar 

  • de la Sierra, A. et al. Prevalence and factors associated with circadian blood pressure patterns in hypertensive patients. Hypertension 53, 466–472 (2009).

    CAS  PubMed  Google Scholar 

  • Toprak, A. et al. Night-time blood pressure load is associated with higher left ventricular mass index in renal transplant recipients. J. Hum.Hypertens. 17, 239–244 (2003).

    CAS  PubMed  Google Scholar 

  • Bacurau, A. V. et al. Sympathetic hyperactivity differentially affects skeletal muscle mass in developing heart failure: role of exercise training. J. Appl. Physiol. (1985) 106, 1631–1640 (2009).

    Google Scholar 

  • Pavlov, V. A. & Tracey, K. J. The vagus nerve and the inflammatory reflex—linking immunity and metabolism. Nat. Rev. Endocrinol. 8, 743–754 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bruchfeld, A. et al. Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis. J. Intern. Med. 268, 94–101 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rollo, C. D. Aging and the mammalian regulatory triumvirate. Aging Dis. 1, 105–138 (2010).

    PubMed  PubMed Central  Google Scholar 

  • Mendelsohn, A. R. & Larrick, J. W. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases. Rejuvenation Res. 16, 518–523 (2013).

    CAS  PubMed  Google Scholar 

  • Bonaz, B. et al. Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway. Neurogastroenterol. Motil. 25, 208–221 (2013).

    CAS  PubMed  Google Scholar 

  • Satapathy, S. K. et al. Galantamine alleviates inflammation and other obesity-associated complications in high-fat diet-fed mice. Mol. Med. 17, 599–606 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yuasa, S., et al. Treatment responses and their predictors in patients with rheumatoid arthritis treated with biological agents. J. Med. Invest. 60, 77–90 (2013).

    PubMed  Google Scholar 

  • Yoshida, S. et al. Infliximab, a TNF-α inhibitor, reduces 24-h ambulatory blood pressure in rheumatoid arthritis patients. J. Hum. Hypertens. 28, 165–169 (2014).

    CAS  PubMed  Google Scholar 

  • Zhao, P. et al. Evening versus morning dosing regimen drug therapy for hypertension. Cochrane Database of Systematic Reviews, Issue 10. Art. No.: CD004184.

  • Perl, J. et al. Sleep disorders in end-stage renal disease: 'markers of inadequate dialysis'? Kidney Int. 70, 1687–1693 (2006).

    CAS  PubMed  Google Scholar 

  • Salminen, A. & Kaarniranta, K. Insulin/IGF-1 paradox of aging: regulation via AKT/IKK/NF-κB signaling. Cell Signal. 22, 573–577 (2010).

    CAS  PubMed  Google Scholar 

  • Lapierre, L. R. & Hansen, M. Lessons from C. elegans: signaling pathways for longevity. Trends Endocrinol. Metab. 23, 637–644 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schiaffino, S. et al. Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 280, 4294–4314 (2013).

    CAS  PubMed  Google Scholar 

  • Doria, A. et al. Autophagy in human health and disease. N. Engl. J. Med. 368, 1845 (2013).

    CAS  PubMed  Google Scholar 

  • Salminen, A. & Kaarniranta, K. Regulation of the aging process by autophagy. Trends. Mol. Med. 15, 217–224 (2009).

    CAS  PubMed  Google Scholar 

  • Salminen, A. et al. Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging (Albany NY) 4, 166–175 (2012).

    CAS  Google Scholar 

  • Roseboom, T. et al. The Dutch famine and its long-term consequences for adult health. Early Hum. Dev. 82, 485–491 (2006).

    PubMed  Google Scholar 

  • Katti, G. et al. Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. Eur. J. Hum. Genet. 10, 682–688 (2002).

    Google Scholar 

  • Thaler, R. et al. Homocysteine suppresses the expression of the collagen cross-linker lysyloxidase involving IL-6, Fli1, and epigenetic DNA methylation. J. Biol. Chem. 286, 5578–5588 (2010).

    PubMed  PubMed Central  Google Scholar 

  • Stenvinkel, P. et al. Impact of inflammation on epigenetic DNA methylation—a novel risk factor for cardiovascular disease? J. Intern. Med. 261, 488–499 (2007).

    CAS  PubMed  Google Scholar 

  • Wang, X. H. & Mitch, W. E. Muscle wasting from kidney failure—a model for catabolic conditions. Int. J. Biochem. Cell. Biol. 45, 2230–2238 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • McIntire, K. L. et al. Acute uremia suppresses leucine-induced signal transduction in skeletal muscle. Kidney Int. 85, 374–382 (2014).

    CAS  PubMed  Google Scholar 

  • Sandri, M. et al. Signalling pathways regulating muscle mass in ageing skeletal muscle. The role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology 14, 303–323 (2013).

    CAS  PubMed  Google Scholar 

  • Reed, S. A. et al. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J. 26, 987–1000 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hussain, S. N. & Sandri, M. Role of autophagy in COPD skeletal muscle dysfunction. J. Appl. Physiol. (1985) 114, 1273–1281 (2013).

    CAS  Google Scholar 

  • Guo, Y. et al. Autophagy in locomotor muscles of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 118, 1313–1320 (2013).

    Google Scholar 

  • Castellano, G. et al. The GH/IGF-1 axis and heart failure. Curr. Cardiol. Rev. 5, 203–215 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stark, M. The sandpile model: optimal stress and hormesis. Dose Response 10, 66–74 (2012).

    PubMed  Google Scholar 

  • Johansen, K. L. et al. Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: a randomized, controlled trial. J. Am. Soc. Nephrol. 17, 2307–2314 (2006).

    CAS  PubMed  Google Scholar 

  • Fouque, D. et al. Recombinant human insulin-like growth factor-1 induces an anabolic response in malnourished CAPD patients. Kidney Int. 57, 646–654 (2000).

    CAS  PubMed  Google Scholar 

  • Kotzmann, H. et al. Differential effects of growth hormone therapy in malnourished hemodialysis patients. Kidney Int. 60, 1578–1585 (2001).

    CAS  PubMed  Google Scholar 

  • Blagosklonny, M. V. Calorie restriction. Decelerating mTOR-driven aging from cells to organisms (including humans). Cell Cycle 9, 683–688 (2010).

    CAS  PubMed  Google Scholar 

  • Mendelsohn, A. R. & Larrick, J. W. Rapamycin as an antiaging therapeutic? Targeting mammalian target of rapamycin to treat Hutchinson-Gilford progeria and neurodegenerative diseases. Rejuvenation Res. 14, 437–441 (2011).

    CAS  PubMed  Google Scholar 

  • Ikizler, T. A. et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int. 84, 1096–1107 (2013).

    CAS  PubMed  Google Scholar 

  • Charansonney, O. L. Physical activity and aging: a life-long story. Discov. Med. 12, 177–185 (2011).

    PubMed  Google Scholar 

  • Sanchis-Gomar, F. Sestrins: novel antioxidant and AMPK-modulating functions regulated by exercise? J. Cell. Physiol. 228, 1647–1650 (2013).

    CAS  PubMed  Google Scholar 

  • Ribeiro, F. et al. Should all patients with COPD be exercise trained? J. Appl. Physiol. (1985) 114, 1300–1308 (2013).

    Google Scholar 

  • Kuro-o, M. A potential link between phosphate and aging-lessons from Klotho-deficient mice. Mech. Ageing Dev. 131, 270–275 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu, M. C. et al. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu. Rev. Physiol. 75, 503–533 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dai, X. Y. et al. Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release. Kidney Int. 83, 1042–1051 (2013).

    CAS  PubMed  Google Scholar 

  • Ketteler, M. et al. Phosphate: a novel cardiovascular risk factor. Eur. Heart J. 34, 1099–1010 (2013).

    PubMed  Google Scholar 

  • Merideth, M. A. et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N. Engl. J. Med. 358, 592–604 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Warren, D. T. & Shanahan, C. M. Defective DNA-damage repair induced by nuclear lamina dysfunction is a key mediator of smooth muscle cell aging. Bioch. Soc. Trans. 39, 1780–1785 (2011).

    CAS  Google Scholar 

  • Villa-Bellasto, R. et al. Defective extracellular pyrophosphate metabolism promotes vascular calcification in a mouse model of Hutchingson-Gilford progeria syndrome that is ameliorated on pyrophosphate treatment. Circulation 127, 2442–2451 (2013).

    Google Scholar 

  • Persy, V. P. & McKee, M. D. Prevention of vascular calcification: is pyrophosphate therapy a solution? Kidney Int. 79, 490–493 (2011).

    CAS  PubMed  Google Scholar 

  • O'Neill, W. C. et al. Treatment with pyrophosphate inhibits uremic vascular calcification. Kidney Int. 79, 512–517 (2011).

    CAS  PubMed  Google Scholar 

  • Bhan, I. Phosphate management in chronic kidney disease. Curr. Opin. Nephrol. Hypertens. 23, 174–179 (2014).

    CAS  PubMed  Google Scholar 

  • Shrikrishna, D. et al. Renin-angiotensin system blockade: a novel therapeutic approach in chronic obstructive pulmonary disease. Clin. Sci. (Lond.) 123, 487–498 (2012).

    CAS  Google Scholar 

  • Flammer, A. J. et al. Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis. Circulation 117, 2262–2269 (2008).

    CAS  PubMed  Google Scholar 

  • Boccara, F. et al. HIV protease inhibitors activate the adipocyte renin angiotensin system. Antivir. Ther. 15, 363–375 (2010).

    CAS  PubMed  Google Scholar 

  • Yoshida, T. et al. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia. Int. J. Biochem. Cell. Biol. 45, 2322–2332 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Titze, J. et al. Spooky sodium balance. Kidney Int. 85, 759–767 (2014).

    CAS  PubMed  Google Scholar 

  • Wiig, H. et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J. Clin. Invest. 123, 2803–2815 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Machnik, A. et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat. Med. 15, 545–552 (2009).

    CAS  PubMed  Google Scholar 

  • Kleinewietfeld, M. et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496, 518–522 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Drüeke, T. B. & Massy, Z. A. Circulating Klotho levels: clinical relevance and relationship with tissue Klotho expression. Kidney Int. 83, 13–15 (2013).

    PubMed  Google Scholar 

  • Lindberg, K. et al. The kidney is the principal organ mediating klotho effects. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2013111209.

  • Razzaque, M. S. The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat. Rev. Endocrinol. 5, 611–619 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Desjardins, L. et al. European Uremic Toxin (EUTox) Work Group. FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages. Osteoporos. Int. 23, 2017–2025 (2012).

    CAS  PubMed  Google Scholar 

  • Sun, C. Y. et al. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 81, 640–650 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tang, C. et al. Downregulation of Klotho expression by dehydration. Am. J. Physiol. Renal Physiol. 301, F745–F750 (2011).

    CAS  PubMed  Google Scholar 

  • Zhou, X., Chen, K., Lei, H. & Sun, Z. Klotho gene deficiency causes salt-sensitive hypertension via monocyte chemotactic protein-1/CC chemokine receptor 2-mediated inflammation. J. Am. Soc Nephrol. http://dx.doi.org/101681/ASN.2013101033.

  • Balasubramanian, P. & Longo, V. D. Linking Klotho, Nrf2, MAP kinases and aging. Aging (Albany NY) 2, 632–633 (2010).

    Google Scholar 

  • Jeong, S. J. et al. Plasma klotho levels were inversely associated with subclinical carotid atherosclerosis in HIV-infected patients receiving combined antiretroviral therapy. AIDS Res. Hum. Retroviruses 29, 1575–1581 (2013).

    CAS  PubMed  Google Scholar 

  • Witkowski, J. M. et al. Klotho—a common link in physiological and rheumatoid arthritis-related aging of human CD4+ lymphocytes. J. Immunol. 178, 771–777 (2007).

    CAS  PubMed  Google Scholar 

  • Semba, R. D. et al. Plasma klotho and cardiovascular disease in adults. J. Am. Geriatr. Soc. 59, 1596–1601 (2011).

    PubMed  PubMed Central  Google Scholar 

  • Semba, R. D. et al. Relationship of low plasma klotho with poor grip strength in older community-dwelling adults: the InCHIANTI study. Eur. J. Appl. Physiol. 112, 1215–1220 (2012).

    PubMed  Google Scholar 

  • Dobnig, H. et al. Independent association of low serum 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch. Intern. Med. 168, 1340–1349 (2008).

    CAS  PubMed  Google Scholar 

  • Richards, J. B. et al. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am. J. Clin. Nutr. 86, 1420–1425 (2007).

    CAS  PubMed  Google Scholar 

  • Lee, S. Y. et al. 25-hydroxyvitamin D levels and vascular calcification in predialysis and dialysis patients with chronic kidney disease. Kidney Blood Press. Res. 3, 349–354 (2012).

    Google Scholar 

  • Argacha, J. F. et al. Vitamin D deficiency-induced hypertension is associated with vascular oxidative stress and altered heart gene expression. J. Cardiovasc. Pharmacol. 58, 65–71 (2011).

    CAS  PubMed  Google Scholar 

  • McGuinness, D. et al. Sirtuins, bioageing, and cancer. J. Aging Res. 2011, 235754 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gomes, A. P. et al. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Saldanha, J. F. et al. Resveratrol: why is it a promising therapy for chronic kidney disease patients? Oxid. Med. Cell. Longev. 2013, 963217 (2013).

    PubMed  PubMed Central  Google Scholar 

  • Momchilova, A. et al. Resveratrol alters the lipid composition, metabolism and peroxide level in senescent rat hepatocytes. Chem. Biol. Interact. 207, 74–80 (2014).

    CAS  PubMed  Google Scholar 

  • Kramer, H. Dietary patterns, calories and kidney disease. Adv. Chr. Kidney Dis. 20, 135–140 (2013).

    Google Scholar 

  • Wolfe, R. A. et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N. Engl. J. Med. 341, 1725–1730 (1999).

    CAS  PubMed  Google Scholar 

  • Ciancolo, G. et al. Importance of vascular calcification in kidney transplant recipients. Am. J. Nephrol. 39, 418–426 (2014).

    Google Scholar 

  • Bahous, S. A. et al. Aortic pulse wave velocity in renal transplant patients. Kidney Int. 66, 1486–1492 (2004).

    PubMed  Google Scholar 

  • van den Ham, E. C. et al. Similarities in skeletal muscle strength and exercise capacity between renal transplant and hemodialysis patients. Am. J. Transplant. 5, 1957–1965 (2005).

    PubMed  Google Scholar 

  • van den Ham, E. C. et al. The functional, metabolic, and anabolic responses to exercise training in renal transplant and hemodialysis patients. Transplantation 83, 1059–1068 (2007).

    PubMed  Google Scholar 

  • Vostálová, J. et al. Stabilization of oxidative stress 1 year after kidney transplantation: effect of calcineurin immunosuppressives. Ren. Fail. 34, 952–959 (2012).

    PubMed  Google Scholar 

  • Nafar, M. Oxidative stress in kidney transplantation: causes, consequences, and potential treatment. Iran. J. Kidney Dis. 5, 357–372 (2011).

    PubMed  Google Scholar 

  • Kunlin, J. Modern biological theories of aging. Aging Dis. 1, 72–74 (2010).

    Google Scholar 

  • Crowley, L. E. et al. Tissue advanced glycation end product deposition after kidney transplantation. Nephron Clin. Pract. 124, 54–59 (2013).

    CAS  PubMed  Google Scholar 

  • Mansell, H. et al. Evidence of enhanced systemic inflammation in stable kidney transplant recipients with low Framingham risk scores. Clin. Transplant. 27, E391–E399 (2013).

    PubMed  Google Scholar 

  • Krajisnik, T. et al. Parathyroid klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients. Kidney Int. 78, 1024–1032 (2010).

    CAS  PubMed  Google Scholar 

  • Tataranni, T. et al. Rapamycin-induced hypophosphatemia and insulin resistance are associated with mTORC2 activation and klotho expression. Am. J. Transpl. 11, 1656–1664 (2011).

    CAS  Google Scholar 

  • Getliffe, K. M. et al. Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: effect of drugs and smoking. Aliment. Pharmacol. Ther. 21, 121–131 (2005).

    CAS  PubMed  Google Scholar 

  • Bauer, M. E. et al. The role of stress factors during aging of the immune system. Ann. NY Acad. Sci. 1153, 139–152 (2009).

    CAS  PubMed  Google Scholar 

  • Muteliefu, G. et al. Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21, and prelamin A through oxidative stress. Am. J. Physiol. Cell. Physiol. 303, C126–C134 (2012).

    CAS  PubMed  Google Scholar 

  • Ragnauth, C. D. et al. Prelamin-A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 121, 2200–2210 (2010).

    CAS  PubMed  Google Scholar 

  • El Assar, M. et al. Oxidative stress and vascular inflammation in aging. Free Radic. Biol. Med. 65, 380–401 (2013).

    CAS  PubMed  Google Scholar 

  • Anthony, D. F. & Shiels, P. G. Exploiting paracrine mechanisms of tissue regeneration to repair damaged organs. Transpl. Proc. 2, 10 (2013).

    CAS  Google Scholar 

  • Martini, S. et al. Integrative biology identifies shared transcriptional networks in CKD. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2013080906.

  • Bousquet, J. et al. Systems medicine and integrated care to combat chronic noncommunicable diseases. Genome Med. 3, 43 (2011).

    PubMed  PubMed Central  Google Scholar 

  • Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 14, R115 (2013).

    PubMed  PubMed Central  Google Scholar 

  • Finkel, T. Radical medicine: treating ageing to cure disease. Nat. Rev. Mol. Cell. Biol. 6, 971–976 (2005).

    CAS  PubMed  Google Scholar 

  • Katsimpardi, L. et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344, 630–634 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sinha, M. et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 344, 649–652 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu, S. C. et al. Testosterone increases renal anti-aging klotho gene expression via the androgen receptor-mediated pathway. Biochem. J. http://dx.doi.org/10.1042/BJ20140739.