Association between telomere length, frailty and death in older adults.
Ageing
Biomarker
Frailty
Functional decline
Mortality
Telomere
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
10
07
2020
accepted:
20
10
2020
pubmed:
16
11
2020
medline:
1
6
2021
entrez:
15
11
2020
Statut:
ppublish
Résumé
Frailty is considered a clinical marker of functional ageing. Telomere length (TL) has been proposed as a biomarker of biological age but its role in human ageing is controversial. The main aim of the study was to evaluate the longitudinal association of TL with incident frailty and mortality in two cohorts of Spanish community-dwelling older adults. TL was determined at baseline in blood samples from older adults included in Toledo Study for Healthy Aging and ENRICA cohorts while frailty was determined by frailty phenotype (FP) at baseline and at follow-up (3.5 years). Deaths occurring during follow-up were also recorded. Associations of TL with frailty and mortality were analysed by logistic regression with progressive adjustment. Data were separately analysed in the two cohorts and in all subjects by performing a meta-analysis. TL was not different between frail and non-frail subjects. Longer telomeres were not associated with lower risk of prevalent frailty. Similarly, TL at baseline failed to predict incident frailty (OR: 1.04 [0.88-1.23]) or even the development of a new FP criterion (OR: 0.97 [0.90-1.05]) at follow-up. Lack of association was also observed when analysing the development of specific FP criteria. Finally, while frailty at baseline was significantly associated with higher risk of death at follow-up (OR: 4.08 [1.97-8.43], p < 0.001), TL did not significantly change the mortality risk (OR: 1.05 [0.94-1.16]). Results show that TL does not predict incident frailty or mortality in older adults. This suggests that TL is not a reliable biomarker of functional age.
Identifiants
pubmed: 33190211
doi: 10.1007/s11357-020-00291-0
pii: 10.1007/s11357-020-00291-0
pmc: PMC8110679
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1015-1027Références
United Nations. World population ageing (2019). https://www.un.org/en/development/desa/population/publications/pdf/ageing/WorldPopulationAgeing2019-Highlights.pdf .
Dzau VJ, Inouye SK, Rowe JW, Finkelman E, Yamada T. Enabling healthful aging for all - the National Academy of Medicine Grand Challenge in Healthy Longevity. N Engl J Med. 2019;381:1699–701. https://doi.org/10.1056/NEJMp1912298 .
doi: 10.1056/NEJMp1912298
pubmed: 31633895
Brivio P, Paladini MS, Racagni G, Riva MA, Calabrese F, Molteni R. From healthy aging to frailty: in search of the underlying mechanisms. Curr Med Chem. 2019;26:3685–701. https://doi.org/10.2174/0929867326666190717152739 .
doi: 10.2174/0929867326666190717152739
pubmed: 31333079
Dent E, Martin FC, Bergman H, Woo J, Romero-Ortuño R, Walston JD. Management of frailty: opportunities, challenges, and future directions. Lancet. 2019;394:1376–86. https://doi.org/10.1016/S0140-6736(19)31785-4 .
doi: 10.1016/S0140-6736(19)31785-4
pubmed: 31609229
Angulo J, El Assar M, Rodriguez-Manas L. Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. Mol Asp Med. 2016;50:1–32. https://doi.org/10.1016/j.mam.2016.06.001 .
doi: 10.1016/j.mam.2016.06.001
Lorenzi M, Bonassi S, Lorenzi T, Giovannini S, Bernabei R, Onder G. A review of telomere length in sarcopenia and frailty. Biogerontology. 2018;19:209–21.
doi: 10.1007/s10522-018-9749-5
pubmed: 29549539
Ferrucci L, Gonzalez-Freire M, Fabbri E, Simonsick E, Tanaka T, Moore Z, et al. Measuring biological aging in humans: a quest. Aging Cell. 2020;19:e13080. https://doi.org/10.1111/acel.13080 .
doi: 10.1111/acel.13080
pubmed: 31833194
Fasching CL. Telomere length measurement as a clinical biomarker of aging and disease. Crit Rev Clin Lab Sci. 2018;55:443–65. https://doi.org/10.1080/10408363.2018.1504274 .
doi: 10.1080/10408363.2018.1504274
pubmed: 30265166
Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361:393–5. https://doi.org/10.1016/S0140-6736(03)12384-7 .
doi: 10.1016/S0140-6736(03)12384-7
pubmed: 12573379
El Assar M, Angulo J, Rodríguez-Mañas L. Frailty as a phenotypic manifestation of underlying oxidative stress. Free Radic Biol Med. 2020;149:72–7. https://doi.org/10.1016/j.freeradbiomed.2019.08.011 .
doi: 10.1016/j.freeradbiomed.2019.08.011
pubmed: 31422077
Yu R, Tang N, Leung J, Woo J. Telomere length is not associated with frailty in older Chinese elderly: cross-sectional and longitudinal analysis. Mech Ageing Dev. 2015;152:74–9. https://doi.org/10.1016/j.mad.2015.10.002 .
doi: 10.1016/j.mad.2015.10.002
pubmed: 26483096
Breitling LP, Saum KU, Perna L, Schottker B, Holleczek B, Brenner H. Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. Clin Epigenetics. 2016;8:21. https://doi.org/10.1186/s13148-016-0186-5 .
doi: 10.1186/s13148-016-0186-5
pubmed: 26925173
pmcid: 4768341
Ortiz-Ramírez M, Sánchez-García S, García-De la Torre P, Reyes-Maldonado E, Sánchez-Arenas R, Rosas-Vargas H. Telomere shortening and frailty in Mexican older adults. Geriatr Gerontol Int. 2018;18:1286–92. https://doi.org/10.1111/ggi.13463 .
doi: 10.1111/ggi.13463
pubmed: 29989281
Vetter VM, Spira D, Banszerus VL, Demuth I. Epigenetic clock and leukocyte telomere length are associated with vitamin D status, but not with functional assessments and frailty in the Berlin Aging Study II. J Gerontol A Biol Sci Med Sci. 2020; (On-line ahead of print). https://doi.org/10.1093/gerona/glaa101 .
García-García FJ, Gutiérrez Avila G, Alfaro-Acha A, et al. The prevalence of frailty syndrome in an older population from Spain. The Toledo Study for Healthy Aging. J Nutr Health Aging. 2011;15:852–6. https://doi.org/10.1007/s12603-011-0075-8 .
doi: 10.1007/s12603-011-0075-8
pubmed: 22159772
Sánchez-Sánchez JL, Izquierdo M, Carnicero-Carreño JA, García-García FJ, Rodríguez-Mañas L. Physical activity trajectories, mortality, hospitalization, and disability in the Toledo Study of Healthy Aging. J Cachexia Sarcopenia Muscle. 2020; (On-line ahead of print). https://doi.org/10.1002/jcsm.12566 .
Rodríguez-Artalejo F, Graciani A, Guallar-Castillón P, León-Muñoz LM, Zuluaga MC, López-García E, et al. Rationale and methods of the study on nutrition and cardiovascular risk in Spain (ENRICA). Rev Esp Cardiol. 2011;64:876–82. https://doi.org/10.1016/j.recesp.2011.05.019 .
doi: 10.1016/j.recesp.2011.05.019
pubmed: 21821340
Ortolá R, Struijk EA, García-Esquinas E, Rodríguez-Artalejo F, López-García E. Changes in dietary intake of animal and vegetable protein and unhealthy aging. Am J Med. 2019;132:1091–102. e9. https://doi.org/10.1016/j.amjmed.2019.06.051 .
doi: 10.1016/j.amjmed.2019.06.051
pubmed: 30981558
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56. https://doi.org/10.1093/gerona/56.3.m146 .
doi: 10.1093/gerona/56.3.m146
pubmed: 11253156
Ottenbacher KJ, Branch LG, Ray L, Gonzales VA, Peek MK, Hinman MR. The reliability of upper- and lower-extremity strength testing in a community survey of older adults. Arch Phys Med Rehabil. 2002;83:1423–7. https://doi.org/10.1053/apmr.2002.34619 .
doi: 10.1053/apmr.2002.34619
pubmed: 12370879
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49:M85–94. https://doi.org/10.1093/geronj/49.2.m85 .
doi: 10.1093/geronj/49.2.m85
pubmed: 8126356
Washburn RA, Smith KW, Jette AM, Janney CA. The physical activity scale for the elderly (PASE): development and evaluation. J Clin Epidemiol. 1993;46:153–62. https://doi.org/10.1016/0895-4356(93)90053-4 .
doi: 10.1016/0895-4356(93)90053-4
pubmed: 8437031
Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA. 1963;185:914–9. https://doi.org/10.1001/jama.1963.03060120024016 .
doi: 10.1001/jama.1963.03060120024016
pubmed: 14044222
de Pedro N, Díez M, García I, García J, Otero L, Fernández L, et al. Analytical Validation of Telomere Analysis Technology® for the high-throughput analysis of multiple telomere-associated variables. Biol Proced Online. 2020;22:2. https://doi.org/10.1186/s12575-019-0115-z .
doi: 10.1186/s12575-019-0115-z
pubmed: 31956299
pmcid: 6961256
Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30:e47. https://doi.org/10.1093/nar/30.10.e47 .
doi: 10.1093/nar/30.10.e47
pubmed: 12000852
pmcid: 115301
O'Callaghan NJ, Fenech M. A quantitative PCR method for measuring absolute telomere length. Biol Proced Online. 2011;13:3. https://doi.org/10.1186/1480-9222-13-3 .
doi: 10.1186/1480-9222-13-3
pubmed: 21369534
pmcid: 3047434
Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48. https://doi.org/10.18637/jss.v036.i03 .
doi: 10.18637/jss.v036.i03
Muezzinler A, Zaineddin AK, Brenner H. A systematic review of leukocyte telomere length and age in adults. Ageing Res Rev. 2013;12:509–19. https://doi.org/10.1016/j.arr.2013.01.003 .
doi: 10.1016/j.arr.2013.01.003
pubmed: 23333817
Blackburn EH, Epel ES, Lin J. Human telomere biology: a contributory and interactive factor in aging, disease risk, and protection. Science. 2015;350:1193–8. https://doi.org/10.1126/science.aab3389 .
doi: 10.1126/science.aab3389
pubmed: 26785477
Svensson J, Karlsson MK, Ljunggren O, Tivesten A, Mellstrom D, Moverare-Skrtic S. Leukocyte telomere length is not associated with mortality in older men. Exp Gerontol. 2014;57:6–12. https://doi.org/10.1016/j.exger.2014.04.013 .
doi: 10.1016/j.exger.2014.04.013
pubmed: 24793325
Needham BL, Rehkopf D, Adler N, Gregorich S, Lin J, Blackburn EH, et al. Leukocyte telomere length and mortality in the National Health and Nutrition Examination Survey, 1999-2002. Epidemiology. 2015;26:528–35. https://doi.org/10.1097/EDE.0000000000000299 .
doi: 10.1097/EDE.0000000000000299
pubmed: 26039272
pmcid: 4679150
Woo J, Yu R, Tang N, Leung J. Telomere length is associated with decline in grip strength in older persons aged 65 years and over. Age (Dordr). 2014;36:9711. https://doi.org/10.1007/s11357-014-9711-7 .
doi: 10.1007/s11357-014-9711-7
Risques RA, Arbeev KG, Yashin AI, Ukraintseva SV, Martin GM, Rabinovitch PS, et al. Leukocyte telomere length is associated with disability in older U.S. population. J Am Geriatr Soc. 2010;58:1289–98. https://doi.org/10.1111/j.1532-5415.2010.02948.x .
doi: 10.1111/j.1532-5415.2010.02948.x
pubmed: 20579170
pmcid: 2918372
Marzetti E, Lorenzi M, Antocicco M, Bonassi S, Celi M, Mastropaolo S, et al. Shorter telomeres in peripheral blood mononuclear cells from older persons with sarcopenia: results from an exploratory study. Front Aging Neurosci. 2014;6:233. https://doi.org/10.3389/fnagi.2014.00233 .
doi: 10.3389/fnagi.2014.00233
pubmed: 25221511
pmcid: 4147848
Saum KU, Dieffenbach AK, Muezzinler A, et al. Frailty and telomere length: cross-sectional analysis in 3537 older adults from the ESTHER cohort. Exp Gerontol. 2014;58:250–5. https://doi.org/10.1016/j.exger.2014.08.009 .
doi: 10.1016/j.exger.2014.08.009
pubmed: 25150678
Zhou J, Wang J, Shen Y, Yang Y, Huang P, Chen S, et al. The association between telomere length and frailty: a systematic review and meta-analysis. Exp Gerontol. 2018;106:16–20. https://doi.org/10.1016/j.exger.2018.02.030 .
doi: 10.1016/j.exger.2018.02.030
pubmed: 29518479
Wang Q, Zhan Y, Pedersen NL, Fang F, Hagg S. Telomere length and all-cause mortality: a meta-analysis. Ageing Res Rev. 2018;48:11–20. https://doi.org/10.1016/j.arr.2018.09.002 .
doi: 10.1016/j.arr.2018.09.002
pubmed: 30254001
Gardner MP, Martin-Ruiz C, Cooper R, Hardy R, Sayer AA, Cooper C, et al. Telomere length and physical performance at older ages: an individual participant meta-analysis. PLoS One. 2013;8:e69526. https://doi.org/10.1371/journal.pone.0069526 .
doi: 10.1371/journal.pone.0069526
pubmed: 23922731
pmcid: 3724915
Haapanen MJ, Perala MM, Salonen MK, et al. Telomere length and frailty: the Helsinki Birth Cohort study. J Am Med Dir Assoc. 2018;19:658–62. https://doi.org/10.1016/j.jamda.2018.05.011 .
doi: 10.1016/j.jamda.2018.05.011
pubmed: 30056950
Diez Roux AV, Ranjit N, Jenny NS, Shea S, Cushman M, Fitzpatrick A, et al. Race/ethnicity and telomere length in the Multi-Ethnic Study of Atherosclerosis. Aging Cell. 2009;8:251–7. https://doi.org/10.1111/j.1474-9726.2009.00470.x .
doi: 10.1111/j.1474-9726.2009.00470.x
pubmed: 19302371
Araujo Carvalho AC, Tavares Mendes ML, da Silva Reis MC, Santos VS, Tanajura DM, Martins-Filho PRS. Telomere length and frailty in older adults-a systematic review and meta-analysis. Ageing Res Rev. 2019;54:100914. https://doi.org/10.1016/j.arr.2019.100914 .
doi: 10.1016/j.arr.2019.100914
pubmed: 31170457
Arts MHL, Collard RM, Comijs HC, de Jonge L, Penninx BWJH, Naarding P, et al. Leucocyte telomere length is no molecular marker of physical frailty in late-life depression. Exp Gerontol. 2018;111:229–34. https://doi.org/10.1016/j.exger.2018.07.016 .
doi: 10.1016/j.exger.2018.07.016
pubmed: 30071286
Zhan Y, Liu XR, Reynolds CA, Pedersen NL, Hagg S, Clements MS. Leukocyte telomere length and all-cause mortality: a between-within twin study with time-dependent effects using generalized survival models. Am J Epidemiol. 2018;187:2186–91. https://doi.org/10.1093/aje/kwy128 .
doi: 10.1093/aje/kwy128
pubmed: 29961868
Martin-Ruiz CM, Gussekloo J, van Heemst D, von Zglinicki T, Westendorp RG. Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population-based study. Aging Cell. 2005;4:287–90. https://doi.org/10.1111/j.1474-9726.2005.00171.x .
doi: 10.1111/j.1474-9726.2005.00171.x
pubmed: 16300480
Rodríguez-Mañas L, Féart C, Mann G, Viña J, Chatterji S, Chodzko-Zajko W, et al. Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. J Gerontol A Biol Sci Med Sci. 2013;68:62–7. https://doi.org/10.1093/gerona/gls119 .
doi: 10.1093/gerona/gls119
pubmed: 22511289
Fitzpatrick AL, Kronmal RA, Kimura M, Gardner JP, Psaty BM, Jenny NS, et al. Leukocyte telomere length and mortality in the Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci. 2011;66:421–9. https://doi.org/10.1093/gerona/glq224 .
doi: 10.1093/gerona/glq224
pubmed: 21289018
Gladyshev VN. Aging progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes. Aging Cell. 2016;15:594–602. https://doi.org/10.1111/acel.12480 .
doi: 10.1111/acel.12480
pubmed: 27060562
pmcid: 4933668
Galkin F, Mamoshina P, Aliper A, de Magalhaes JP, Gladyshev VN, Zhavoronkov A. Biohorology and biomarkers of aging: current state-of-the-art, challenges and opportunities. Ageing Res Rev. 2020;60:101050. https://doi.org/10.1016/j.arr.2020.101050 .
doi: 10.1016/j.arr.2020.101050
pubmed: 32272169