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A preliminary candidate approach identifies the combination of chemerin, fetuin-A, and fibroblast growth factors 19 and 21 as a potential biomarker panel of successful aging

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Abstract

Although the number of centenarians is growing worldwide, the potential factors influencing the aging process remain only partially elucidated. Researchers are increasingly focusing toward biomarkers as tools to shed more light on the pathophysiology of complex phenotypes, including the ability to reach successful aging, i.e., free of major chronic diseases. We therefore conducted a case-control study examining the potential associations of multiple candidate biomarkers in healthy centenarians and sex-matched healthy elderly controls. Using a case-control study of 81 centenarians (aged ≥ 100 years) selected based on the fact that they were disease-free and 46 healthy elderly controls (aged 70–80 years), serum levels of 15 different candidate biomarkers involved in the regulation of metabolism, angiogenesis, inflammation, and bone formation were measured. Of the 15 biomarkers tested, four molecules (chemerin, fetuin-A, and fibroblast growth factors [FGF] 19 and 21) were found to be independently associated with successful aging regardless of sex. Logistic regression analysis confirmed that chemerin, fetuin-A, FGF19, and FGF21 were independently associated with successful aging [predicted probability (PP) = 1 / [1 + 1 / exp (11.832 − 0.027 × (chemerin) − 0.009 × (fetuin-A) + 0.014 × (FGF19) − 0.007 × (FGF21)]. The area under the curve (AUC) of predicted probability values for the four-biomarker panel revealed that it can discriminate between centenarians and elderly controls with excellent accuracy (AUC > 0.94, P < 0.001). Although preliminary in essence and limited by the low sample size and lack of replication in other independent cohorts, our data suggest an independent association between successful aging and serum chemerin, fetuin-A, FGF19, and FGF21, which may provide novel information on the mechanisms behind the human aging process. Whether the four-biomarker panel may predict successful aging deserves further scrutiny.

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References

  • Adams AC, Cheng CC, Coskun T, Kharitonenkov A (2012) FGF21 requires betaklotho to act in vivo. PLoS ONE 7:e49977

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ailshire JA, Beltran-Sanchez H, Crimmins EM (2014) Becoming Centenarians: Disease and Functioning Trajectories of Older U.S. Adults as They Survive to 100. J Gerontol A Biol Sci Med Sci

  • Barutcuoglu B, Basol G, Cakir Y, Cetinkalp S, Parildar Z, Kabaroglu C, Ozmen D, Mutaf I, Bayindir O (2011) Fibroblast growth factor-19 levels in type 2 diabetic patients with metabolic syndrome. Ann Clin Lab Sci 41:390–396

    CAS  PubMed  Google Scholar 

  • Basile G, Paffumi I, D’Angelo AG, Figliomeni P, Cucinotta MD, Pace E, Ferraro M, Saitta S, Lasco A, Gangemi S (2012) Healthy centenarians show high levels of circulating interleukin-22 (IL-22). Arch Gerontol Geriatr 54:459–461

    Article  CAS  PubMed  Google Scholar 

  • Bik W, Baranowska-Bik A, Wolinska-Witort E, Kalisz M, Broczek K, Mossakowska M, Baranowska B (2013) Assessment of adiponectin and its isoforms in Polish centenarians. Exp Gerontol 48:401–407

    Article  CAS  PubMed  Google Scholar 

  • Christensen K, McGue M, Petersen I, Jeune B, Vaupel JW (2008) Exceptional longevity does not result in excessive levels of disability. Proc Natl Acad Sci U S A 105:13274–13279

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Emanuele E, Lista S, Ghidoni R, Binetti G, Cereda C, Benussi L, Maletta R, Bruni AC, Politi P (2011) Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer’s disease. Neurobiol Aging 32:1231–1235

    Article  CAS  PubMed  Google Scholar 

  • Emanuele E, Minoretti P, Pareja-Galeano H, Sanchis-Gomar F, Garatachea N, Lucia A (2014a) Serum irisin levels, precocious myocardial infarction, and healthy exceptional longevity. Am J Med 127:888–890

    Article  CAS  PubMed  Google Scholar 

  • Emanuele E, Minoretti P, Sanchis-Gomar F, Pareja-Galeano H, Yilmaz Y, Garatachea N , Lucia A (2014b) Can Enhanced Autophagy be Associated with Human Longevity? Serum Levels of the Autophagy Biomarker Beclin-1 are Increased in Healthy Centenarians. Rejuvenation Res

  • Fang Q, Li H, Song Q, Yang W, Hou X, Ma X, Lu J, Xu A, Jia W (2013) Serum fibroblast growth factor 19 levels are decreased in Chinese subjects with impaired fasting glucose and inversely associated with fasting plasma glucose levels. Diabetes Care 36:2810–2814

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fatima SS, Rehman R, Baig M, Khan TA (2014) New roles of the multidimensional adipokine: Chemerin. Peptides 62C:15–20

    Article  Google Scholar 

  • Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191

    Article  PubMed  Google Scholar 

  • Gangemi S, Basile G, Merendino RA, Minciullo PL, Novick D, Rubinstein M, Dinarello CA, Lo Balbo C, Franceschi C, Basili S, DU E, Davi G, Nicita-Mauro V, Romano M (2003) Increased circulating Interleukin-18 levels in centenarians with no signs of vascular disease: another paradox of longevity? Exp Gerontol 38:669–672

    Article  CAS  PubMed  Google Scholar 

  • Gavrilova NS, Gavrilov LA (2010) Search for mechanisms of exceptional human longevity. Rejuvenation Res 13:262–264

    Article  PubMed Central  PubMed  Google Scholar 

  • Gerli R, Monti D, Bistoni O, Mazzone AM, Peri G, Cossarizza A, Di Gioacchino M, Cesarotti ME, Doni A, Mantovani A, Franceschi C, Paganelli R (2000) Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev 121:37–46

    Article  CAS  PubMed  Google Scholar 

  • Geroldi D, Falcone C, Minoretti P, Emanuele E, Arra M, D’Angelo A (2006) High levels of soluble receptor for advanced glycation end products may be a marker of extreme longevity in humans. J Am Geriatr Soc 54:1149–1150

    Article  PubMed  Google Scholar 

  • Gremeaux V, Gayda M, Lepers R, Sosner P, Juneau M, Nigam A (2012) Exercise and longevity. Maturitas 73:312–317

    Article  PubMed  Google Scholar 

  • Hao Y, Zhou J, Zhou M, Ma X, Lu Z, Gao M, Pan X, Tang J, Bao Y, Jia W (2013) Serum levels of fibroblast growth factor 19 are inversely associated with coronary artery disease in chinese individuals. PLoS ONE 8:e72345

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Heinrichsdorff J, Olefsky JM (2012) Fetuin-A: the missing link in lipid-induced inflammation. Nat Med 18:1182–1183

    Article  CAS  PubMed  Google Scholar 

  • Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ (2011) FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science 331:1621–1624

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kuro-o M (2010) Klotho. Pflugers Arch 459:333–343

    Article  CAS  PubMed  Google Scholar 

  • Leeson GW (2014) Future prospects for longevity. Post Reprod Health 20:11–15

    Article  PubMed  Google Scholar 

  • Malin SK, Navaneethan SD, Mulya A, Huang H, Kirwan JP (2014) Exercise-induced lowering of chemerin is associated with reduced cardiometabolic risk and glucose-stimulated insulin secretion in older adults. J Nutr Health Aging 18:608–615

    Article  CAS  PubMed  Google Scholar 

  • Mathews ST, Rakhade S, Zhou X, Parker GC, Coscina DV, Grunberger G (2006) Fetuin-null mice are protected against obesity and insulin resistance associated with aging. Biochem Biophys Res Commun 350:437–443

    Article  CAS  PubMed  Google Scholar 

  • Mori K, Emoto M, Inaba M (2012) Fetuin-A and the cardiovascular system. Adv Clin Chem 56:175–195

    Article  CAS  PubMed  Google Scholar 

  • Nolen B, Velikokhatnaya L, Marrangoni A, De Geest K, Lomakin A, Bast RC Jr, Lokshin A (2010) Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol 117:440–445

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rasul S, Wagner L, Kautzky-Willer A (2012) Fetuin-A and angiopoietins in obesity and type 2 diabetes mellitus. Endocrine 42:496–505

    Article  CAS  PubMed  Google Scholar 

  • Robert L, Fulop T (2014) Longevity and its regulation: centenarians and beyond. Interdiscip Top Gerontol 39:198–211

    Article  CAS  PubMed  Google Scholar 

  • Stefanov T, Bluher M, Vekova A, Bonova I, Tzvetkov S, Kurktschiev D, Temelkova-Kurktschiev T (2014) Circulating chemerin decreases in response to a combined strength and endurance training. Endocrine 45:382–391

    Article  CAS  PubMed  Google Scholar 

  • Terry DF, Sebastiani P, Andersen SL, Perls TT (2008) Disentangling the roles of disability and morbidity in survival to exceptional old age. Arch Intern Med 168:277–283

    Article  PubMed Central  PubMed  Google Scholar 

  • Tomiyama K, Maeda R, Urakawa I, Yamazaki Y, Tanaka T, Ito S, Nabeshima Y, Tomita T, Odori S, Hosoda K, Nakao K, Imura A (2010) Relevant use of Klotho in FGF19 subfamily signaling system in vivo. Proc Natl Acad Sci U S A 107:1666–1671

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Trost SG, Fees BS, Haar SJ, Murray AD, Crowe LK (2012) Identification and validity of accelerometer cut-points for toddlers. Obesity (Silver Spring) 20:2317–2319

    Article  Google Scholar 

  • Wang D, Zhu W, Li J, An C, Wang Z (2013) Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history. PLoS ONE 8:e81190

    Article  PubMed Central  PubMed  Google Scholar 

  • Wojcik M, Janus D, Dolezal-Oltarzewska K, Kalicka-Kasperczyk A, Poplawska K, Drozdz D, Sztefko K, Starzyk JB (2012) A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents. J Pediatr Endocrinol Metab 25:1089–1093

    CAS  PubMed  Google Scholar 

  • Woo YC, Xu A, Wang Y, Lam KS (2013) Fibroblast growth factor 21 as an emerging metabolic regulator: clinical perspectives. Clin Endocrinol (Oxf) 78:489–496

    Article  CAS  Google Scholar 

  • Wu AL, Coulter S, Liddle C, Wong A, Eastham-Anderson J, French DM, Peterson AS, Sonoda J (2011) FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways. PLoS ONE 6:e17868

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, Katafuchi T, Xiao G, Potthoff MJ, Wei W, Wan Y, Yu RT, Evans RM, Kliewer SA, Mangelsdorf DJ (2012) The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. Elife 1:e00065

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Conflicts of interest

None declared. All listed authors have made a significant research contribution to the study and approved the submission.

Author information

Authors and Affiliations

  1. Research Institute of Hospital 12 de Octubre (‘i+12’), Avda. de Córdoba s/n, 28041, Madrid, Spain

    Fabian Sanchis-Gomar, Helios Pareja-Galeano, Alejandro Santos-Lozano, Nuria Garatachea, Carmen Fiuza-Luces & Alejandro Lucia

  2. Universidad Europea de Madrid, Madrid, Spain

    Helios Pareja-Galeano, Carmen Fiuza-Luces & Alejandro Lucia

  3. Facultad de Ciencias de la Salud y del Deporte, Universidad de Zaragoza, Huesca, Spain

    Nuria Garatachea

  4. Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

    Letizia Venturini & Giovanni Ricevuti

  5. Cellular Pathophysiology and Clinical Immunology Laboratory, University of Pavia, Pavia, Italy

    Letizia Venturini & Giovanni Ricevuti

  6. 2E Science. Robbio, Pavia, Italy

    Enzo Emanuele

Authors
  1. Fabian Sanchis-Gomar
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  2. Helios Pareja-Galeano
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  3. Alejandro Santos-Lozano
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  4. Nuria Garatachea
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  5. Carmen Fiuza-Luces
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  6. Letizia Venturini
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  7. Giovanni Ricevuti
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  8. Alejandro Lucia
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  9. Enzo Emanuele
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Correspondence to Fabian Sanchis-Gomar.

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Alejandro Lucia and Enzo Emanuele share senior authorship.

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Sanchis-Gomar, F., Pareja-Galeano, H., Santos-Lozano, A. et al. A preliminary candidate approach identifies the combination of chemerin, fetuin-A, and fibroblast growth factors 19 and 21 as a potential biomarker panel of successful aging. AGE 37, 42 (2015). https://doi.org/10.1007/s11357-015-9776-y

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