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AGE

, 36:9639 | Cite as

Select aging biomarkers based on telomere length and chronological age to build a biological age equation

  • Wei-Guang Zhang
  • Shu-Ying Zhu
  • Xiao-Juan Bai
  • De-Long Zhao
  • Shi-Min Jiang
  • Juan Li
  • Zuo-Xiang Li
  • Bo Fu
  • Guang-Yan Cai
  • Xue-Feng SunEmail author
  • Xiang-Mei ChenEmail author
Article

Abstract

The purpose of this study is to build a biological age (BA) equation combining telomere length with chronological age (CA) and associated aging biomarkers. In total, 139 healthy volunteers were recruited from a Chinese Han cohort in Beijing. A genetic index, renal function indices, cardiovascular function indices, brain function indices, and oxidative stress and inflammation indices (C-reactive protein [CRP]) were measured and analyzed. A BA equation was proposed based on selected parameters, with terminal telomere restriction fragment (TRF) and CA as the two principal components. The selected aging markers included mitral annulus peak E anterior wall (MVEA), intima-media thickness (IMT), cystatin C (CYSC), D-dimer (DD), and digital symbol test (DST). The BA equation was: BA = −2.281TRF + 26.321CYSC + 0.025DD − 104.419MVEA + 34.863IMT − 0.265DST + 0.305CA + 26.346. To conclude, telomere length and CA as double benchmarks may be a new method to build a BA.

Keywords

Telomere length Biological age Chronological age Aging markers 

Notes

Acknowledgments

We are grateful for those who participated in this research. This work was supported by the National Basic Research Program of China (No. 2103CB530800) and the National Key Technology R&D Program (No. 2011BAI10B00).

References

  1. AihieSayer A, Osmond C, Briggs R, Cooper C (1999) Do all systems age together? Gerontology 45(2):83–86CrossRefGoogle Scholar
  2. Bae C-Y, Kang YG, Kim S, Cho C, Kang HC, Yu BY, Lee S-W, Cho KH, Lee DC, Lee K (2008) Development of models for predicting biological age (BA) with physical, biochemical, and hormonal parameters. Arch Gerontol Geriatr 47(2):253–265PubMedCrossRefGoogle Scholar
  3. Bai X, Han L, Liu Q, Shan H, Lin H, Sun X, Chen X (2010) Evaluation of biological aging process—a population-based study of healthy people in China. Gerontology 56(2):129–140PubMedCrossRefGoogle Scholar
  4. Baker GT 3rd, Sprott RL (1988) Biomarkers of aging. Exp Gerontol 23(4–5):223–239PubMedCrossRefGoogle Scholar
  5. Baldassarre D, Veglia F, Hamsten A, Humphries SE, Rauramaa R, de Faire U, Smit AJ, Giral P, Kurl S, Mannarino E (2013) Progression of carotid intima-media thickness as predictor of vascular events results from the IMPROVE study. Arterioscler Thromb Vasc Biol 33(9):2273–2279PubMedCrossRefGoogle Scholar
  6. Bansal N, Whooley MA, Regan M, McCulloch CE, Ix JH, Epel E, Blackburn E, Lin J, C-y H (2012) Association between kidney function and telomere length: the heart and soul study. Am J Nephrol 36(5):405–411PubMedCentralPubMedCrossRefGoogle Scholar
  7. Bekaert S, De Meyer T, Van Oostveldt P (2005) Telomere attrition as ageing biomarker. Anticancer Res 25(4):3011–3021PubMedGoogle Scholar
  8. Benetos A, Okuda K, Lajemi M, Kimura M, Thomas F, Skurnick J, Labat C, Bean K, Aviv A (2001) Telomere length as an indicator of biological aging the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 37(2):381–385PubMedCrossRefGoogle Scholar
  9. Blackburn EH (1991) Structure and function of telomeres. Nature 350(6319):569–573PubMedCrossRefGoogle Scholar
  10. Blagosklonny MV (2009) Validation of anti-aging drugs by treating age-related diseases. Aging 1(3):281PubMedCentralPubMedGoogle Scholar
  11. Boonekamp JJ, Simons MJ, Hemerik L, Verhulst S (2013) Telomere length behaves as biomarker of somatic redundancy rather than biological age. Aging Cell 2(2):330–332CrossRefGoogle Scholar
  12. Butler RN, Sprott R, Warner H, Bland J, Feuers R, Forster M, Fillit H, Harman SM, Hewitt M, Hyman M (2004) Biomarkers of aging: from primitive organisms to humans. J Gerontol Ser A 59:560–567CrossRefGoogle Scholar
  13. Cuende JI, Cuende N, Calaveras-Lagartos J (2010) How to calculate vascular age with the SCORE project scales: a new method of cardiovascular risk evaluation. Eur Heart J 31(19):2351–2358PubMedCrossRefGoogle Scholar
  14. De Meyer T, Rietzschel ER, De Buyzere ML, Langlois MR, De Bacquer D, Segers P, Van Damme P, De Backer GG, Van Oostveldt P, Van Criekinge W (2009) Systemic telomere length and preclinical atherosclerosis: the Asklepios Study. Eur Heart J 30(24):3074–3081PubMedCrossRefGoogle Scholar
  15. Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40(2):221–226PubMedCrossRefGoogle Scholar
  16. Dubina TL, Mints AYa, Zhuk, EV (1984) Biological age and its estimation. III. Introduction of a correction to the multiple regression model of biological age in cross-sectional and longitudinal studies. Exp Gerontol 19(2):133–143Google Scholar
  17. Emberson J, Haynes R, Dasgupta T, Mafham M, Landray M, Baigent C, Clarke R (2010) Cystatin C and risk of vascular and nonvascular mortality: a prospective cohort study of older men. J Intern Med 268(2):145–154PubMedCrossRefGoogle Scholar
  18. Fitzpatrick AL, Kronmal RA, Gardner JP, Psaty BM, Jenny NS, Tracy RP, Walston J, Kimura M, Aviv A (2007) Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol 165(1):14–21PubMedCrossRefGoogle Scholar
  19. Fossel M (2012) Use of telomere length as a biomarker for aging and age-related disease. Curr Transl Geriatr Gerontol Rep 1(2):121–127CrossRefGoogle Scholar
  20. Guarente L, Kenyon C (2000) Genetic pathways that regulate ageing in model organisms. Nature 408(6809):255–262PubMedCrossRefGoogle Scholar
  21. Guinot C, Malvy DJ-M, Ambroisine L, Latreille J, Mauger E, Tenenhaus M, Morizot F, Lopez S, Le Fur I, Tschachler E (2002) Relative contribution of intrinsic vs extrinsic factors to skin aging as determined by a validated skin age score. Arch Dermatol 138(11):1454PubMedCrossRefGoogle Scholar
  22. Gunn DA, Rexbye H, Griffiths CE, Murray PG, Fereday A, Catt SD, Tomlin CC, Strongitharm BH, Perrett DI, Catt M (2009) Why some women look young for their age. PLoS ONE 4(12):e8021PubMedCentralPubMedCrossRefGoogle Scholar
  23. Gupta M, Divyashree R, Abhilash P, Bijle MNA, Murali K (2013) Correlation between chronological age, dental age and skeletal age among monozygoyic and dizygotic twins. J Int Oral Health: JIOH 5(1):16PubMedCentralPubMedGoogle Scholar
  24. Hägg U, Matsson L (1985) Dental maturity as an indicator of chronological age: the accuracy and precision of three methods. Eur J Orthod 7(1):25PubMedCrossRefGoogle Scholar
  25. Halcox JP, Donald AE, Ellins E, Witte DR, Shipley MJ, Brunner EJ, Marmot MG, Deanfield JE (2009) Endothelial function predicts progression of carotid intima-media thickness. Circulation 119(7):1005–1012PubMedCrossRefGoogle Scholar
  26. Harris SE, Deary IJ, MacIntyre A, Lamb KJ, Radhakrishnan K, Starr JM, Whalley LJ, Shiels PG (2006) The association between telomere length, physical health, cognitive ageing, and mortality in non-demented older people. Neurosci Lett 406(3):260–264PubMedCrossRefGoogle Scholar
  27. Hodkinson H (1972) Evaluation of a mental test score for assessment of mental impairment in the elderly. Age Ageing 1(4):233–238PubMedCrossRefGoogle Scholar
  28. Hodkinson H (2012) Evaluation of a mental test score for assessment of mental impairment in the elderly. Age Ageing 41(suppl_3):iii35–iii40PubMedCrossRefGoogle Scholar
  29. Hollingsworth JW, Hashizume A, Jablon S (1965) Correlations between tests of aging in Hiroshima subjects—an attempt to define "physiologic age". Yale J Biol Med 38(1):11PubMedCentralPubMedGoogle Scholar
  30. Hong S-J, Lui CSM, Hahn J, Moon JY, Kim TK (2013) How old are you really? Cognitive age in technology acceptance. Decis Support Syst 56:122–130Google Scholar
  31. Jee H, Jeon BH, Kim YH, Kim H-K, Choe J, Park J, Jin Y (2012) Development and application of biological age prediction models with physical fitness and physiological components in Korean adults. Gerontology 58(4):344–353PubMedCrossRefGoogle Scholar
  32. Johnson TE (2006) Recent results: biomarkers of aging. Exp Gerontol 41(12):1243–1246PubMedCrossRefGoogle Scholar
  33. Jones DM, Song X, Rockwood K (2004) Operationalizing a frailty index from a standardized comprehensive geriatric assessment. J Am Geriatr Soc 52(11):1929–1933PubMedCrossRefGoogle Scholar
  34. Lee M, Saver JL, Huang W-H, Chow J, Chang K-H, Ovbiagele B (2010) Impact of elevated cystatin C level on cardiovascular disease risk in predominantly high cardiovascular risk populations a meta-analysis. Circ: Cardiovasc Qual Outcome 3(6):675–683Google Scholar
  35. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217PubMedCentralPubMedCrossRefGoogle Scholar
  36. MacDonald SWS, Dixon RA, Cohen AL, Hazlitt JE (2004) Biological age and 12-year cognitive change in older adults: findings from the Victoria longitudinal study. Gerontology 50(2):64–81PubMedCrossRefGoogle Scholar
  37. Majkić-Singh N (2011) What is a biomarker? From its discovery to clinical application. J Med Biochem 30(3):186–192Google Scholar
  38. Mak K (2013) The normal physiology of aging. Colorectal cancer in the elderly. Springer, HeidelbergGoogle Scholar
  39. Mather KA, Jorm AF, Milburn PJ, Tan X, Easteal S, Christensen H (2010) No associations between telomere length and age-sensitive indicators of physical function in mid and later life. J Gerontol A: Biol Med Sci 65(8):792–799CrossRefGoogle Scholar
  40. Mather KA, Jorm AF, Parslow RA, Christensen H (2011) Is telomere length a biomarker of aging? A review. J Gerontol A: Biol Med Sci 66(2):202–213CrossRefGoogle Scholar
  41. McClearn GE (1997) Biomarkers of age and aging. Exp Gerontol 32(1–2):87–94PubMedCrossRefGoogle Scholar
  42. Mitchell BD, Hsueh WC, King TM, Pollin TI, Sorkin J, Agarwala R, SchaÈffer AA, Shuldiner AR (2001) Heritability of life span in the Old Order Amish. Am J Med Genet 102(4):346–352PubMedCrossRefGoogle Scholar
  43. Mitnitski A, Song X, Rockwood K (2013) Assessing biological aging: the origin of deficit accumulation. Biogerontology 14(6):709–717Google Scholar
  44. Mooradian AD (1990) Biomarkers of aging: do we know what to look for? J Gerontol 45(6):B183–B186PubMedCrossRefGoogle Scholar
  45. Müezzinler A, Zaineddin AK, Brenner H (2013) A systematic review of leukocyte telomere length and age in adults. Ageing Res Rev 12(2):509–519PubMedCrossRefGoogle Scholar
  46. Nakamura E, Miyao K (2007) A method for identifying biomarkers of aging and constructing an index of biological age in humans. J Gerontol A: Biol Med Sci 62(10):1096–1105CrossRefGoogle Scholar
  47. Nakamura E, Miyao K (2008) Sex differences in human biological aging. J Gerontol A: Biol Med Sci 63(9):936–944CrossRefGoogle Scholar
  48. Nakamura E, Miyao K, Ozeki T (1988) Assessment of biological age by principal component analysis. Mech Ageing Dev 46(1):1–18PubMedCrossRefGoogle Scholar
  49. Nakamura E, Lane MA, Roth GS, Cutler RG, Ingram DK (1994) Evaluating measures of hematology and blood chemistry in male rhesus monkeys as biomarkers of aging. Exp Gerontol 29(2):151–177PubMedCrossRefGoogle Scholar
  50. Nakamura E, Lane MA, Roth GS, Ingram DK (1998) A strategy for identifying biomarkers of aging: further evaluation of hematology and blood chemistry data from a calorie restriction study in rhesus monkeys. Exp Gerontol 33(5):421–443PubMedCrossRefGoogle Scholar
  51. O’Donnell CJ, Demissie S, Kimura M, Levy D, Gardner JP, White C, D’Agostino RB, Wolf PA, Polak J, Cupples LA (2008) Leukocyte telomere length and carotid artery intimal medial thickness the Framingham heart study. Arterioscler Thromb Vasc Biol 28(6):1165–1171PubMedCentralPubMedCrossRefGoogle Scholar
  52. Park J, Cho B, Kwon H, Lee C (2009) Developing a biological age assessment equation using principal component analysis and clinical biomarkers of aging in Korean men. Arch Gerontol Geriatr 49(1):7–12PubMedCrossRefGoogle Scholar
  53. Polak JF, Pencina MJ, O'Leary DH, D'Agostino RB (2011) Common carotid artery intima-media thickness progression as a predictor of stroke in multi-ethnic study of atherosclerosis. Stroke 42(11):3017–3021PubMedCentralPubMedCrossRefGoogle Scholar
  54. Pradhan AD, LaCroix AZ, Langer RD, Trevisan M, Lewis CE, Hsia JA, Oberman A, Kotchen JM, Ridker PM (2004) Tissue plasminogen activator antigen and D-dimer as markers for atherothrombotic risk among healthy postmenopausal women. Circulation 110(3):292–300PubMedCrossRefGoogle Scholar
  55. Quinn T, Gallacher J, Deary I, Lowe G, Fenton C, Stott D (2011) Association between circulating hemostatic measures and dementia or cognitive impairment: systematic review and meta‐analyzes. J Thromb Haemost 9(8):1475–1482PubMedCrossRefGoogle Scholar
  56. Rattan SI (2013) Healthy ageing, but what is health? Biogerontology 14(6):673–677Google Scholar
  57. Reff ME, Schneider EL, Health E-UNIo (1982) Biological markers of aging. Dept. of Health and Human ServicesGoogle Scholar
  58. Rippon I, Kneale D, de Oliveira C, Demakakos P, Steptoe A (2013) Perceived age discrimination in older adults. Age Ageing. doi: 10.1093/ageing/aft146 PubMedCentralPubMedGoogle Scholar
  59. Saeed M, Berlin RM, Cruz TD (2012) Exploring the utility of genetic markers for predicting biological age. Legal Med 14(6):279–285PubMedCrossRefGoogle Scholar
  60. Sanders JL, Newman AB (2013) Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither? Epidemiol Rev 35(1):112–131CrossRefGoogle Scholar
  61. Sanders JL, Cauley JA, Boudreau RM, Zmuda JM, Strotmeyer ES, Opresko PL, Hsueh WC, Cawthon RM, Li R, Harris TB (2009) Leukocyte telomere length is not associated with BMD, osteoporosis, or fracture in older adults: results from the health, aging and body composition study. J Bone Miner Res 24(9):1531–1536PubMedCentralPubMedCrossRefGoogle Scholar
  62. Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K (2008) A standard procedure for creating a frailty index. BMC Geriatr 8(1):24PubMedCentralPubMedCrossRefGoogle Scholar
  63. Simm A, Johnson TE (2010) Biomarkers of ageing: a challenge for the future. Exp Gerontol 45(10):731–732PubMedCrossRefGoogle Scholar
  64. Skytthe A, Pedersen NL, Kaprio J, Stazi MA, Iachine I, Vaupel JW, Christensen K (2003) Longevity studies in GenomEUtwin. Twin Res 6(5):448–454PubMedCrossRefGoogle Scholar
  65. Sprott RL (2010) Biomarkers of aging and disease: introduction and definitions. Exp Gerontol 45(1):2–4PubMedCrossRefGoogle Scholar
  66. Sternberg SA, Wershof Schwartz A, Karunananthan S, Bergman H, Clarfield AM (2011) The identification of frailty: a systematic literature review. J Am Geriatr Soc 59(11):2129–2138PubMedCrossRefGoogle Scholar
  67. Tang N, Woo J, Suen E, Liao C, Leung J, Leung P (2010) The effect of telomere length, a marker of biological aging, on bone mineral density in elderly population. Osteoporos Int 21(1):89–97PubMedCrossRefGoogle Scholar
  68. Tita-Nwa F, Bos A, Adjei A, Ershler WB, Longo DL, Ferrucci L (2010) Correlates of D-dimer in older persons. Aging Clin Exp Res 22(1):20PubMedCentralPubMedCrossRefGoogle Scholar
  69. Tsuji A, Ishiko A, Takasaki T, Ikeda N (2002) Estimating age of humans based on telomere shortening. Forensic Sci Int 126(3):197–199PubMedCrossRefGoogle Scholar
  70. Ueno LM, Yamashita Y, Moritani T, Nakamura E (2003) Biomarkers of aging in women and the rate of longitudinal changes. J Physiol Anthropol Appl Hum Sci 22(1):37–46CrossRefGoogle Scholar
  71. Valdes A, Richards J, Gardner J, Swaminathan R, Kimura M, Xiaobin L, Aviv A, Spector T (2007) Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis. Osteoporos Int 18(9):1203–1210PubMedCrossRefGoogle Scholar
  72. Valdes A, Deary I, Gardner J, Kimura M, Lu X, Spector T, Aviv A, Cherkas L (2010) Leukocyte telomere length is associated with cognitive performance in healthy women. Neurobiol Aging 31(6):986–992PubMedCentralPubMedCrossRefGoogle Scholar
  73. Wannamethee SG, Whincup PH, Lennon L, Rumley A, Lowe GD (2012) Fibrin D-dimer, tissue-type plasminogen activator, von Willebrand factor, and risk of incident stroke in older men. Stroke 43(5):1206–1211PubMedCrossRefGoogle Scholar
  74. Yashin AI, Iachine IA, Harris JR (1999) Half of the variation in susceptibility to mortality is genetic: findings from Swedish twin survival data. Behav Genet 29(1):11–19PubMedCrossRefGoogle Scholar
  75. Yashin AI, Arbeev KG, Akushevich I, Arbeeva L, Kravchenko J, Il’yasova D, Kulminski A, Akushevich L, Culminskaya I, Wu D (2010) Dynamic determinants of longevity and exceptional health. Curr Gerontol Geriatr Res. doi: 10.1155/2010/381637
  76. Zglinicki T, Martin-Ruiz C (2005) Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med 5(2):197–203CrossRefGoogle Scholar
  77. Zhang Z, Lu B, Sheng X, Jin N (2011) Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am J Kidney Dis 58(3):356–365PubMedCrossRefGoogle Scholar
  78. Zhang WG, Bai XJ, Sun XF, Cai GY, Bai XY, Zhu SY, Zhang M, Chen XM (2014) Construction of an integral formula of biological age for a healthy chinese population using principle component analysis. J Nutr Health Aging. 18(2):137–142Google Scholar

Copyright information

© American Aging Association 2014

Authors and Affiliations

  • Wei-Guang Zhang
    • 1
  • Shu-Ying Zhu
    • 2
  • Xiao-Juan Bai
    • 3
  • De-Long Zhao
    • 1
  • Shi-Min Jiang
    • 1
  • Juan Li
    • 4
  • Zuo-Xiang Li
    • 1
  • Bo Fu
    • 1
  • Guang-Yan Cai
    • 1
  • Xue-Feng Sun
    • 1
    Email author
  • Xiang-Mei Chen
    • 1
    Email author
  1. 1.Department of Nephrology, State Key Laboratory of Kidney Diseases (2011DAV00088), State Chronic Kidney Disease Clinical Research Center (2013BAI09B05)Chinese PLA General HospitalBeijingChina
  2. 2.Department of NephrologyThe Second Affiliated Hospital of Nanchang Medical UniversityNanchangChina
  3. 3.Departments of Gerontology and GeriatricsShengjing Hospital of China Medical UniversityShenyangChina
  4. 4.Department of CardiovascularChinese PLA General Hospital, State Key Laboratory of Kidney DiseasesBeijingChina

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