Evaluation of potential aging biomarkers in healthy individuals: telomerase, AGEs, GDF11/15, sirtuin 1, NAD+, NLRP3, DNA/RNA damage, and klotho

. 2023 Dec ; 24 (6) : 937-955. [epub] 20230731

Jazyk angličtina Země Nizozemsko Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid37523061
Odkazy

PubMed 37523061
PubMed Central PMC10615959
DOI 10.1007/s10522-023-10054-x
PII: 10.1007/s10522-023-10054-x
Knihovny.cz E-zdroje

Aging is a natural process of gradual decrease in physical and mental capacity. Biological age (accumulation of changes and damage) and chronological age (years lived) may differ. Biological age reflects the risk of various types of disease and death from any cause. We selected potential biomarkers of aging - telomerase, AGEs, GDF11 and 15 (growth differentiation factor 11/15), sirtuin 1, NAD+ (nicotinamide adenine dinucleotide), inflammasome NLRP3, DNA/RNA damage, and klotho to investigate changes in their levels depending on age and sex. We included 169 healthy volunteers and divided them into groups according to age (under 35; 35-50; over 50) and sex (male, female; male and female under 35; 35-50, over 50). Markers were analyzed using commercial ELISA kits. We found differences in values depending on age and gender. GDF15 increased with age (under 30 and 35-50 p < 0.002; 35-50 and over 50; p < 0.001; under 35 and over 50; p < 0.001) as well as GDF11 (35-50 and over 50; p < 0.03; under 35 and over 50; p < 0.02), AGEs (under 30 and 35-50; p < 0.005), NLRP3 (under 35 over 50; p < 0.03), sirtuin 1 (35-50 and over 50; p < 0.0001; under 35 and over 50; p < 0.004). AGEs and GDF11 differed between males and females. Correlations were identified between individual markers, markers and age, and markers and sex. Markers that reflect the progression of biological aging vary with age (GDF15, GDF11, AGEs, NLRP3, sirtuin) and sex (AGEs, GDF11). Their levels could be used in clinical practice, determining biological age, risk of age-related diseases and death of all-causes, and initiating or contraindicating a therapy in the elderly based on the patient's health status.

Zobrazit více v PubMed

Akhter F, Chen D, Akhter A, Yan SF, Du YSS. Age-dependent accumulation of dicarbonyls and advanced glycation endproducts (AGEs) associates with mitochondrial stress. Free Radic Biol Med. 2021;164:429–438. doi: 10.1016/J.FREERADBIOMED.2020.12.021. PubMed DOI PMC

Alcazar J, Frandsen U, Prokhorova T, et al. Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia study. J Cachexia Sarcopenia Muscle. 2021;12(6):1418. doi: 10.1002/JCSM.12823. PubMed DOI PMC

Alves-Fernandes DK, Jasiulionis MG. The role of SIRT1 on DNA damage response and epigenetic alterations in cancer. Int J Mol Sci. 2019;20(13):3153. doi: 10.3390/IJMS20133153. PubMed DOI PMC

Amaro-Gahete FJ, De-la-O A, Jurado-Fasoli L, Gutiérrez Á, Ruiz JR, Castillo MJ. Association of physical activity and fitness with S-Klotho plasma levels in middle-aged sedentary adults: the FIT-AGEING study. Maturitas. 2019;123:25–31. doi: 10.1016/j.maturitas.2019.02.001. PubMed DOI

Añón-Hidalgo J, Catalán V, Rodríguez A, et al. Circulating GDF11 levels are decreased with age but are unchanged with obesity and type 2 diabetes. Aging. 2019;11(6):1733–1744. doi: 10.18632/aging.101865. PubMed DOI PMC

Bodiga VL, Eda SR, Bodiga S. Advanced glycation end products: role in pathology of diabetic cardiomyopathy. Hear Fail Rev. 2013;19(1):49–63. doi: 10.1007/S10741-013-9374-Y. PubMed DOI

Borska L, Kremlacek J, Andrys C, et al. Systemic inflammation, oxidative damage to nucleic acids, and metabolic syndrome in the pathogenesis of psoriasis. Int J Mol Sci. 2017 doi: 10.3390/IJMS18112238. PubMed DOI PMC

Brenière C, Méloux A, Pédard M, et al. Growth Differentiation Factor-15 (GDF-15) is associated with mortality in ischemic stroke patients treated with acute revascularization therapy. Front Neurol. 2019;10:611. doi: 10.3389/FNEUR.2019.00611/BIBTEX. PubMed DOI PMC

Buchanan S, Combet E, Stenvinkel P, Shiels PG. Klotho, Aging, and the failing kidney. Front Endocrinol. 2020;11:560. doi: 10.3389/FENDO.2020.00560/BIBTEX. PubMed DOI PMC

Chaudhuri J, Bains Y, Guha S, et al. The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality. Cell Metab. 2018;28(3):337–352. doi: 10.1016/j.cmet.2018.08.014. PubMed DOI PMC

Chen L, Luo G, Liu Y, et al. Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity. Cell Death Dis. 2021 doi: 10.1038/S41419-021-03954-8. PubMed DOI PMC

Chuang YC, Chen SD, Jou SB, et al. Sirtuin 1 regulates mitochondrial biogenesis and provides an endogenous neuroprotective mechanism against seizure-induced neuronal cell death in the hippocampus following status epilepticus. Int J Mol Sci. 2019;20(14):3588. doi: 10.3390/ijms20143588. PubMed DOI PMC

Clemens Z, Sivakumar S, Pius A, et al. The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function. Elife. 2021 doi: 10.7554/ELIFE.61138. PubMed DOI PMC

Clement J, Wong M, Poljak A, Sachdev P, Braidy N. The plasma NAD+ metabolome is dysregulated in “normal” aging. Rejuvenation Res. 2019;22(2):121. doi: 10.1089/REJ.2018.2077. PubMed DOI PMC

Cohen E, Margalit I, Shochat T, Goldberg E, Krause I. Markers of chronic inflammation in overweight and obese individuals and the role of gender: a cross-sectional study of a large cohort. J Inflamm Res. 2021;14:567–573. doi: 10.2147/JIR.S294368. PubMed DOI PMC

Colleluori G, Villareal DT. Aging, obesity, sarcopenia and the effect of diet and exercise intervention. Exp Gerontol. 2021;155:111561. doi: 10.1016/j.exger.2021.111561. PubMed DOI PMC

Colloca G, Di Capua B, Bellieni A, et al. Biological and functional biomarkers of aging: definition, characteristics, and how they can impact everyday cancer treatment. Curr Oncol Rep. 2020;22(11):1–12. doi: 10.1007/S11912-020-00977-W/TABLES/3. PubMed DOI PMC

Conte M, Martucci M, Mosconi G, et al. GDF15 plasma level is inversely associated with level of physical activity and correlates with markers of inflammation and muscle weakness. Front Immunol. 2020 doi: 10.3389/fimmu.2020.00915. PubMed DOI PMC

Cornelius C, Trovato Salinaro A, Scuto M, et al. Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes. Immun Ageing. 2013 doi: 10.1186/1742-4933-10-41. PubMed DOI PMC

Ebert H, Lacruz ME, Kluttig A, et al. Advanced glycation end products and their ratio to soluble receptor are associated with limitations in physical functioning only in women: results from the CARLA cohort. BMC Geriatr. 2019;19(1):1–8. doi: 10.1186/S12877-019-1323-8/FIGURES/2. PubMed DOI PMC

Egerman MA, Glass DJ. The role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis. Crit Rev Biochem Mol Biol. 2019 doi: 10.1080/10409238.2019.1610722. PubMed DOI

Freeman DW, Noren Hooten N, Kim Y, et al. Association between GDF15, poverty and mortality in urban middle-aged African American and white adults. PLoS One. 2020;15(8):e0237059. doi: 10.1371/JOURNAL.PONE.0237059. PubMed DOI PMC

Fujita Y, Taniguchi Y, Shinkai S, Tanaka M, Ito M. Secreted growth differentiation factor 15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders. Geriatr Gerontol Int. 2016;16:17–29. doi: 10.1111/GGI.12724. PubMed DOI

Gaudioso G, Collotta D, Chiazza F, et al. Advanced glycation end products (AGEs) in metabolic disease: linking diet, inflammation and microbiota. Proc Nutr Soc. 2020 doi: 10.1017/S002966512000316X. PubMed DOI PMC

González-Dominguez A, Montañez R, Castejón-Vega B, et al. Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson-Gilford Progeria. EMBO Mol Med. 2021;13(10):e14012. doi: 10.15252/EMMM.202114012. PubMed DOI PMC

Gonzalez-Hunt CP, Wadhwa M, Sanders LH. DNA damage by oxidative stress: measurement strategies for two genomes. Curr Opin Toxicol. 2018;7:87–94. doi: 10.1016/J.COTOX.2017.11.001. DOI

Gritsenko A, Green JP, Brough D, Lopez-Castejon G. Mechanisms of NLRP3 priming in inflammaging and age related diseases. Cytokine Growth Factor Rev. 2020;55:15–25. doi: 10.1016/j.cytogfr.2020.08.003. PubMed DOI PMC

Hartmann A, Hartmann C, Secci R, Hermann A, Fuellen G, Walter M. Ranking Biomarkers of aging by citation profiling and effort scoring. Front Genet. 2021 doi: 10.3389/FGENE.2021.686320/FULL. PubMed DOI PMC

Hartmann A, Hartmann C, Secci R, Hermann A, Fuellen G, Walter M. Ranking biomarkers of aging by citation profiling and effort scoring. Front Genet. 2021 doi: 10.3389/FGENE.2021.686320. PubMed DOI PMC

Hertzog RG, Popescu DM, Călborean O. Telomerase level: a useful tool to predict longevity. J Aging Sci. 2021;9(3):1–4. doi: 10.35248/2329-8847.21.9.251. DOI

Hosseninia S, Ameli A, Aslani MR, Pourfarzi F, Ghobadi H. Serum levels of sirtuin-1 in patients with lung cancer and its association with karnofsky performance status. Acta Biomed. 2021 doi: 10.23750/ABM.V92I2.10712. PubMed DOI PMC

Imai SI, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464–471. doi: 10.1016/J.TCB.2014.04.002. PubMed DOI PMC

Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2(1):16017. doi: 10.1038/NPJAMD.2016.17. PubMed DOI PMC

Jia Q, Liu B, Dang X, et al. Growth differentiation factor-11 downregulates steroidogenic acute regulatory protein expression through ALK5-mediated SMAD3 signaling pathway in human granulosa-lutein cells. Reprod Biol Endocrinol. 2022;20(1):1–13. doi: 10.1186/s12958-022-00912-7. PubMed DOI PMC

Johann K, Kleinert M, Klaus S. The role of gdf15 as a myomitokine. Cells. 2021;10(11):2990. doi: 10.3390/cells10112990. PubMed DOI PMC

Jylhävä J, Pedersen NL, Hägg S. Biol Age Predictors Ebiomed. 2017;21:29–36. doi: 10.1016/J.EBIOM.2017.03.046. PubMed DOI PMC

Kane AE, Sinclair DA. Sirtuins and NAD+ in the development and treatment of metabolic and cardiovascular diseases. Circ Res. 2018;123(7):868–885. doi: 10.1161/CIRCRESAHA.118.312498. PubMed DOI PMC

Karas A, Holmannova D, Borsky P, et al. Significantly altered serum levels of NAD, AGE, RAGE, CRP, and elastin as potential biomarkers of psoriasis and aging—a case-control study. Biomedicines. 2022;10(5):1133. doi: 10.3390/BIOMEDICINES10051133. PubMed DOI PMC

Kaur I, Rawal P, Rohilla S, et al. Endothelial progenitor cells from aged subjects display decreased expression of sirtuin 1, angiogenic functions, and increased senescence. Cell Biol Int. 2018;42(9):1212–1220. doi: 10.1002/CBIN.10999. PubMed DOI

Khanh VC, Zulkifli AF, Tokunaga C, Yamashita T, Hiramatsu Y, Ohneda O. Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1. Biochem Biophys Res Commun. 2018;500(3):682–690. doi: 10.1016/J.BBRC.2018.04.136. PubMed DOI

Kidir V, Aynali A, Altuntas A, et al. Actividad de la telomerasa en pacientes en etapas de 2–5D con enfermedad renal crónica. Nefrol. 2017;37(6):592–597. doi: 10.1016/J.NEFRO.2017.03.025. PubMed DOI

Kilhovd BK, Juutilainen A, Lehto S, et al. High serum levels of advanced glycation end products predict increased coronary heart disease mortality in nondiabetic women but not in nondiabetic men: a population-based 18-year follow-up study. Arterioscler Thromb Vasc Biol. 2005;25(4):815–820. doi: 10.1161/01.ATV.0000158380.44231.FE. PubMed DOI

Kilic U, Gok O, Erenberk U, et al. A remarkable age-related increase in sirt1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PLoS One. 2015;10(3):e0117954. doi: 10.1371/JOURNAL.PONE.0117954. PubMed DOI PMC

Lagunas-Rangel FA. Current role of mammalian sirtuins in DNA repair. DNA Repair. 2019;80:85–92. doi: 10.1016/j.dnarep.2019.06.009. PubMed DOI

Liu J, He MH, Peng J, et al. Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast. Aging. 2016;8(11):2827–2847. doi: 10.18632/aging.101095. PubMed DOI PMC

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2022 doi: 10.1016/J.CELL.2022.11.001. PubMed DOI

Manetti M, Rosa I, Fioretto BS, Matucci-Cerinic M, Romano E. Decreased serum levels of SIRT1 and SIRT3 correlate with severity of skin and lung fibrosis and peripheral microvasculopathy in systemic sclerosis. J Clin Med. 2022;11(5):1362. doi: 10.3390/jcm11051362. PubMed DOI PMC

Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012 doi: 10.1371/journal.pone.0042357. PubMed DOI PMC

McNally EJ, Luncsford PJ, Armanios M. Long telomeres and cancer risk: the price of cellular immortality. J Clin Invest. 2019;129(9):3474–3481. doi: 10.1172/JCI120851. PubMed DOI PMC

Milan-Mattos JC, Anibal FF, Perseguini NM, et al. Effects of natural aging and gender on pro-inflammatory markers. Brazilian J Med Biol Res. 2019 doi: 10.1590/1414-431x20198392. PubMed DOI PMC

Mostafidi E, Moeen A, Nasri H, Hagjo AG, Ardalan M. Serum klotho levels in trained athletes. Nephro-Urology Mon. 2018;8(1):30245. doi: 10.5812/NUMONTHLY.30245. PubMed DOI PMC

Navarro-Pando JM, Alcocer-Gómez E, Castejón-Vega B, et al. Inhibition of the NLRP3 inflammasome prevents ovarian aging. Sci Adv. 2021 doi: 10.1126/SCIADV.ABC7409/SUPPL_FILE/ABC7409_SM.PDF. PubMed DOI PMC

Niedrist T, Pailer S, Jahrbacher R, Gruber H-J, Herrmann M, Renner W. Intensity-dependent stimulation of leukocyte telomerase activity by endurance exercise—a pilot study. LaboratoriumsMedizin. 2022;46(3):179–185. doi: 10.1515/LABMED-2022-0054. DOI

Noureen N, Wu S, Lv Y, et al. Integrated analysis of telomerase enzymatic activity unravels an association with cancer stemness and proliferation. Nat Commun. 2021;12(1):1–11. doi: 10.1038/s41467-020-20474-9. PubMed DOI PMC

Palacios JA, Herranz D, De Bonis ML, Velasco S, Serrano M, Blasco MA. SIRT1 contributes to telomere maintenance and augments global homologous recombination. J Cell Biol. 2010;191(7):1299–1313. doi: 10.1083/JCB.201005160. PubMed DOI PMC

Poggioli T, Vujic A, Yang P, et al. Circulating growth differentiation factor 11/8 levels decline with age. Circ Res. 2016;118(1):29–37. doi: 10.1161/CIRCRESAHA.115.307521. PubMed DOI PMC

Preston J, Biddell B. The physiology of ageing and how these changes affect older people. Medicine. 2021;49(1):1–5. doi: 10.1016/J.MPMED.2020.10.011. DOI

Razgonova MP, Zakharenko AM, Golokhvast KS, et al. Telomerase and telomeres in aging theory and chronographic aging theory (review) Mol Med Rep. 2020;22(3):1679–1694. doi: 10.3892/mmr.2020.11274. PubMed DOI PMC

Rungratanawanich W, Qu Y, Wang X, Essa MM, Song BJ. Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury. Exp Mol Med. 2021;53(2):168–188. doi: 10.1038/s12276-021-00561-7. PubMed DOI PMC

Sanz B, Arrieta H, Rezola-Pardo C, et al. Low serum klotho concentration is associated with worse cognition, psychological components of frailty, dependence, and falls in nursing home residents. Sci Reports. 2021;11(1):1–10. doi: 10.1038/s41598-021-88455-6. PubMed DOI PMC

Schafer MJ, Atkinson EJ, Vanderboom PM, et al. Quantification of GDF11 and myostatin in human aging and cardiovascular disease. Cell Metab. 2016;23(6):1207–1215. doi: 10.1016/j.cmet.2016.05.023. PubMed DOI PMC

Schiewer MJ, Knudsen KE. Linking DNA damage and hormone signaling pathways in cancer. Trends Endocrinol Metab. 2016;27(4):216–225. doi: 10.1016/J.TEM.2016.02.004. PubMed DOI PMC

Schwarzmann L, Pliquett RU, Simm A, Bartling B. 2021. Sex-related differences in human plasma NAD+/NADH levels depend on age. Biosci Rep. PubMed DOI PMC

Sharifi-Zahabi E, Sharafabad FH, Abdollahzad H, Malekahmadi M, Rad NB. Circulating advanced glycation end products and their soluble receptors in relation to all-cause and cardiovascular mortality: a systematic review and meta-analysis of prospective observational studies. Adv Nutr. 2021;12(6):2157–2171. doi: 10.1093/ADVANCES/NMAB072. PubMed DOI PMC

Song L, Wu F, Li C, Zhang S. Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway. Biogerontology. 2022 doi: 10.1007/s10522-022-09967-w. PubMed DOI PMC

Stamatovic SM, Martinez-Revollar G, Hu A, Choi J, Keep RF, Andjelkovic AV. Decline in Sirtuin-1 expression and activity plays a critical role in blood-brain barrier permeability in aging. Neurobiol Dis. 2019;126:105–116. doi: 10.1016/j.nbd.2018.09.006. PubMed DOI PMC

Tan KCB, Shiu SWM, Wong Y, Tam X. Serum advanced glycation end products (AGEs) are associated with insulin resistance. Diabetes Metab Res Rev. 2011;27(5):488–492. doi: 10.1002/DMRR.1188. PubMed DOI

Tanaka R, Koarai A, Yamada M, et al. Longitudinal relationship between growth differentiation factor 11 and physical activity in chronic obstructive pulmonary disease. Int J COPD. 2021;16:999–1006. doi: 10.2147/COPD.S301690. PubMed DOI PMC

Tsuchiya T, Takei A, Tsujikado K, Inukai T. Effects of androgens and estrogens on sirtuin 1 gene expression in human aortic endothelial cells. Saudi Med J. 2020;41(4):361. doi: 10.15537/SMJ.2020.4.25006. PubMed DOI PMC

Ullah M, Sun Z, Hare JM. Klotho deficiency accelerates stem cells aging by impairing telomerase activity. J Gerontol—Ser A Biol Sci Med Sci. 2019;74(9):1396–1407. doi: 10.1093/gerona/gly261. PubMed DOI PMC

Vaiserman A, Krasnienkov D. Telomere length as a marker of biological age: state-of-the-art, open issues, and future perspectives. Front Genet. 2021;11:1816. doi: 10.3389/fgene.2020.630186. PubMed DOI PMC

Wang DX, Zhu XD, Ma XR, et al. Loss of growth differentiation factor 11 shortens telomere length by downregulating telomerase activity. Front Physiol. 2021;12:1501. doi: 10.3389/FPHYS.2021.726345/BIBTEX. PubMed DOI PMC

Wischhusen J, Melero I, Fridman WH. Growth/differentiation factor-15 (GDF-15): from biomarker to novel targetable immune checkpoint. Front Immunol. 2020;11:951. doi: 10.3389/FIMMU.2020.00951/BIBTEX. PubMed DOI PMC

Xu C, Wang L, Fozouni P, et al. SIRT1 is downregulated by autophagy in senescence and ageing. Nat Cell Biol. 2020;22(10):1170–1179. doi: 10.1038/s41556-020-00579-5. PubMed DOI PMC

Yang F, Deng X, Yu Y, et al. Association of human whole blood NAD+ Contents with aging. Front Endocrinol. 2022;13:318. doi: 10.3389/FENDO.2022.829658/BIBTEX. PubMed DOI PMC

Youm YH, Kanneganti TD, Vandanmagsar B, et al. The NLRP3 inflammasome promotes age-related thymic demise and immunosenescence. Cell Rep. 2012;1(1):56–68. doi: 10.1016/J.CELREP.2011.11.005. PubMed DOI PMC

Zbroch E, Bazyluk A, Malyszko J, et al. The serum concentration of anti-aging proteins, sirtuin1 and αKlotho in patients with end-stage kidney disease on maintenance hemodialysis. Clin Interv Aging. 2020;15:387–393. doi: 10.2147/CIA.S236980. PubMed DOI PMC

Zhang C, Lin Y, Zhang K, et al. GDF11 enhances therapeutic functions of mesenchymal stem cells for angiogenesis. Stem Cell Res Ther. 2021;12(1):1–17. doi: 10.1186/S13287-021-02519-Y/FIGURES/8. PubMed DOI PMC

Zhao L, Zhang S, Cui J, et al. TERT assists GDF11 to rejuvenate senescent VEGFR2+/CD133+ cells in elderly patients with myocardial infarction. Lab Investig. 2019;99(11):1661–1688. doi: 10.1038/s41374-019-0290-1. PubMed DOI

Zhu HZ, Zhang LY, Zhai ME, et al. GDF11 alleviates pathological myocardial remodeling in diabetic cardiomyopathy through SIRT1-dependent regulation of oxidative stress and apoptosis. Front Cell Dev Biol. 2021;9:1644. doi: 10.3389/fcell.2021.686848. PubMed DOI PMC

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...