Age-related Decline in Renal Function is Attenuated in Master Athletes

Abstract

This study analyzed the kidney function and biomarkers of health in lifelong-trained sprinters and endurance runners, and compared them to untrained aged-matched and young controls. Sixty-two men (21–66 yr.) were recruited and allocated as master athletes from sprints (n=25), master athletes from endurance events (n=8), untrained middle-aged (n=14) and young controls (n=15). Participants underwent anamnesis, anthropometric measures and blood sampling for biochemical analyses of klotho, FGF23 and estimated glomerular filtration rate. Master sprinters presented better kidney function in relation to endurance athletes and their untrained peers (P<0.0001). A number of biochemical variables were observed that negatively (i. e., GDF-15, TGF-Beta, IL-18) or positively (i. e., klotho/FGF23 ratio and sestrin-2) correlated with eGFR. Sestrin-2 presented the strongest association with eGFR (r=0.5, P=0.03). Results also revealed that lifelong-trained individuals presented the highest probability of having better values for cystatin C and thus an estimated glomerular filtration rate that was 37–49% higher than untrained peers. Master sprinters presented better kidney function in relation to endurance athletes and middle-aged untrained peers. Sestrin-2 may play a role in exercise-induced kidney function protection.

Key words

klotho - sestrin - FGF-23 - inflammation - oxidative stress - runners

Publication History

Received: 04 June 2020

Accepted: 25 November 2020

Article published online:
08 March 2021

• References

• 1 Kalyani RR, Golden SH, Cefalu WT. Diabetes and aging: Unique considerations and goals of care. Diabetes Care 2017; 40: 440-443
• 2 Laiteerapong N, Ham SA, Gao Y. et al. The legacy effect in type 2 diabetes: Impact of early glycemic control on future complications (the Diabetes & Aging Study). Diabetes Care 2019; 42: 416-426
• 3 Najjar SS, Scuteri A, Lakatta EG. Arterial aging: Is it an immutable cardiovascular risk factor?. Hypertension 2005; 46: 454-462
• 4 Nakayama H, Nishida K, Otsu K. Macromolecular degradation systems and cardiovascular aging. Circ Res 2016; 118: 1577-1592
• 5 Levey AS, Coresh J. Chronic kidney disease. Lancet 2012; 379: 165-180
• 6 Levey AS, Eckardt K-U, Tsukamoto Y. et al. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005; 67: 2089-2100
• 7 Jenny NS. Inflammation in aging: cause, effect, or both?. Discov Med 2012; 13: 451-460
• 8 Romano AD, Serviddio G, De Matthaeis A. et al. Oxidative stress and aging. J Nephrol 2010; 23: S29-S36
• 9 Kurosu H, Ogawa Y, Miyoshi M. et al. Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem 2006; 281: 6120-6123
• 10 Raj DS, Pecoits-Filho R, Kimmel PL. Inflammation in chronic kidney disease. In: Kimmel P, Rosenberg M. Chronic Renal Disease. 2nd ed.. Amsterdam: Elsevier; 2020: 355-373
• 11 Zhao Y, Banerjee S, Dey N. et al. Klotho depletion contributes to increased inflammation in kidney of the db/db mouse model of diabetes via RelA (serine) 536 phosphorylation. Diabetes 2011; 60: 1907-1916
• 12 Anatoliotakis N, Deftereos S, Bouras G. et al. Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease. Curr Top Med Chem 2013; 13: 115-138
• 13 Litvinov D, Mahini H, Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. N Am J Med Sci 2012; 4: 523–532
• 14 Niess A, Dickhuth H, Northoff H. et al. Free radicals and oxidative stress in exercise–immunological aspects. Exerc Immunol Rev 1999; 5: 22-56
• 15 Woods JA, Wilund KR, Martin SA. et al. Exercise, inflammation and aging. Aging Dis 2012; 3: 130
• 16 Zouhal H, Jabbour G, Jacob C. et al. Anaerobic and aerobic energy system contribution to 400-m flat and 400-m hurdles track running. J Strength Cond Res 2010; 24: 2309-2315
• 17 Lepers R, Stapley PJ. Master athletes are extending the limits of human endurance. Front Physiol 2016; 7: 613
• 18 Dubé JJ, Broskey NT, Despines AA. et al. Muscle characteristics and substrate energetics in lifelong endurance athletes. Med Sci Sports Exerc 2016; 48: 472–480
• 19 Aguiar SS, Sousa CV, Deus LA. et al. Oxidative stress, inflammatory cytokines and body composition of master athletes: The interplay. Exp Gerontol 2020; 130: 110806
• 20 Rittweger J, di Prampero PE, Maffulli N. et al. Sprint and endurance power and ageing: An analysis of master athletic world records. Proc Biol Sci 2009; 276: 683-689
• 21 Bagley L, McPhee JS, Ganse B. et al. Similar relative decline in aerobic and anaerobic power with age in endurance and power master athletes of both sexes. Scand J Med Sci Sports 2019; 29: 791-799
• 22 da Silva Aguiar S, Sousa CV, Sales MM. et al. Age-related decrease in performance of male masters athletes in sprint, sprint-endurance, and endurance events. Sport Sci Health 2020; 385-392
• 23 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817 doi:10.1055/a-1015-3123
• 24 Pedersen L, Pedersen SM, Brasen CL. et al. Soluble serum klotho levels in healthy subjects. Comparison of two different immunoassays. Clin Biochem 2013; 46: 1079-1083
• 25 Larsson A, Malm J, Grubb A. et al. Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L. Scan J Clin Lab Invest 2004; 64: 25-30
• 26 Cockcroft DW, Gault H. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41
• 27 Kusy K, Zielinski J. Sprinters versus long-distance runners: how to grow old healthy. 2015; 43: 57-64
• 28 Calles-Escandon J, Cunningham JJ, Snyder P. et al. Influence of exercise on urea, creatinine, and 3-methylhistidine excretion in normal human subjects. Am J Physiol 1984; 246: E334-E338
• 29 Refsum H, Strömme S. Urea and creatinine production and excretion in urine during and after prolonged heavy exercise. Scan J Clin Lab Invest 1974; 33: 247-254
• 30 Moll K, Gussew A, Nisser M. et al. Comparison of metabolic adaptations between endurance-and sprint-trained athletes after an exhaustive exercise in two different calf muscles using a multi-slice 31P-MR spectroscopic sequence. NMR Biomed 2018; 31: e3889
• 31 Zieliński J, Slominska EM, Król-Zielińska M. et al. Purine metabolism in sprint-vs endurance-trained athletes aged 20–90 years. Sci Rep 2019; 9: 12075
• 32 Corrêa HL, Neves RVP, Deus LA. et al. Blood flow restriction training blunts chronic kidney disease progression in humans. Med Sci Sports Exerc 2021;
• 33 Moraes MR, Rosa TS, Souza MK. et al. Resistance training downregulates macrophages infiltration in the kidney of 5/6 nephrectomized rats. Life Sci 2018; 213: 190-197
• 34 Souza MK, Neves RVP, Rosa TS. et al. Resistance training attenuates inflammation and the progression of renal fibrosis in chronic renal disease. Life Sci 2018; 206: 93-97
• 35 Passos CS, Ribeiro RS, Rosa TS. et al. Cardiovascular and renal effects of birdseed associated with aerobic exercise in rats. Med Sci Sports Exerc 2016; 48: 1925-1934
• 36 Kim M, Sujkowski A, Namkoong S. et al. Sestrins are evolutionarily conserved mediators of exercise benefits. Nat Commun 2020; 11: 190
• 37 Lee JH, Budanov AV, Park EJ. et al. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 2010; 327: 1223-1228
• 38 Lee JH, Budanov AV, Karin M. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab 2013; 18: 792-801
• 39 Spada TC, Silva JM, Francisco LS. et al. High intensity resistance training causes muscle damage and increases biomarkers of acute kidney injury in healthy individuals. PLoS One 2018; 13: e0205791