Publication

Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases

Cardoso, A. L., Fernandes, A., Aguilar-Pimentel, J. A., de Angelis, M. H., Guedes, J. R., Brito, M. A., Ortolano, S., Pani, G., Athanasopoulou, S., Gonos, E. S., Schosserer, M., Grillari, J., Peterson, P., Tuna, B. G., Dogan, S., Meyer, A., van Os, R. & Trendelenburg, A-U., Nov-2018, In : Ageing Research Reviews. 47, p. 214-277 64 p.

Research output: Contribution to journalReview articleAcademicpeer-review

APA

Cardoso, A. L., Fernandes, A., Aguilar-Pimentel, J. A., de Angelis, M. H., Guedes, J. R., Brito, M. A., Ortolano, S., Pani, G., Athanasopoulou, S., Gonos, E. S., Schosserer, M., Grillari, J., Peterson, P., Tuna, B. G., Dogan, S., Meyer, A., van Os, R., & Trendelenburg, A-U. (2018). Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases. Ageing Research Reviews, 47, 214-277. https://doi.org/10.1016/j.arr.2018.07.004

Author

Cardoso, Ana Luisa ; Fernandes, Adelaide ; Aguilar-Pimentel, Juan Antonio ; de Angelis, Martin Hrabe ; Guedes, Joana Ribeiro ; Brito, Maria Alexandra ; Ortolano, Saida ; Pani, Giovambattista ; Athanasopoulou, Sophia ; Gonos, Efstathios S. ; Schosserer, Markus ; Grillari, Johannes ; Peterson, Part ; Tuna, Bilge Guvenc ; Dogan, Soner ; Meyer, Angelika ; van Os, Ronald ; Trendelenburg, Anne-Ulrike. / Towards frailty biomarkers : Candidates from genes and pathways regulated in aging and age-related diseases. In: Ageing Research Reviews. 2018 ; Vol. 47. pp. 214-277.

Harvard

Cardoso, AL, Fernandes, A, Aguilar-Pimentel, JA, de Angelis, MH, Guedes, JR, Brito, MA, Ortolano, S, Pani, G, Athanasopoulou, S, Gonos, ES, Schosserer, M, Grillari, J, Peterson, P, Tuna, BG, Dogan, S, Meyer, A, van Os, R & Trendelenburg, A-U 2018, 'Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases', Ageing Research Reviews, vol. 47, pp. 214-277. https://doi.org/10.1016/j.arr.2018.07.004

Standard

Towards frailty biomarkers : Candidates from genes and pathways regulated in aging and age-related diseases. / Cardoso, Ana Luisa; Fernandes, Adelaide; Aguilar-Pimentel, Juan Antonio; de Angelis, Martin Hrabe; Guedes, Joana Ribeiro; Brito, Maria Alexandra; Ortolano, Saida; Pani, Giovambattista; Athanasopoulou, Sophia; Gonos, Efstathios S.; Schosserer, Markus; Grillari, Johannes; Peterson, Part; Tuna, Bilge Guvenc; Dogan, Soner; Meyer, Angelika; van Os, Ronald; Trendelenburg, Anne-Ulrike.

In: Ageing Research Reviews, Vol. 47, 11.2018, p. 214-277.

Research output: Contribution to journalReview articleAcademicpeer-review

Vancouver

Cardoso AL, Fernandes A, Aguilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA et al. Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases. Ageing Research Reviews. 2018 Nov;47:214-277. https://doi.org/10.1016/j.arr.2018.07.004


BibTeX

@article{4265af8828044ea48fa158929efd461c,
title = "Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases",
abstract = "Objective: Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel.Methods: Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several {"}hallmark of aging{"} pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six {"}hallmark of aging{"} pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers.Results: A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified.Conclusion: Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) CXCL10 (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), CX3CL1 (C-X3-C motif chemokine ligand 1), (2) GDF15 (growth differentiation factor 15), FNDC5 (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) PLAU (plasminogen activator, urokinase), AGT (angiotensinogen), (5) BDNF (brain derived neurotrophic factor), progranulin (PGRN), (6) alpha-klotho (KL), FGF23 (fibroblast growth factor 23), FGF21, leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), AHCY (adenosylhomocysteinase) and KRT18 (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin alpha, (2) APP (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) S100B (S100 calcium binding protein B), (4) TGF beta (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), TGM2 (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), HMGB1 (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (REIN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.",
keywords = "Frailty, Biomarker panel, Hallmark of aging pathways, Age-related diseases, GROWTH-FACTOR 21, GLYCATION END-PRODUCTS, DIFFERENTIATION FACTOR 15, TERMINAL-AGRIN FRAGMENT, CHRONIC KIDNEY-DISEASE, NF-KAPPA-B, PLASMINOGEN-ACTIVATOR INHIBITOR-1, MILD COGNITIVE IMPAIRMENT, FATTY LIVER-DISEASE, CHRONIC HEART-FAILURE",
author = "Cardoso, {Ana Luisa} and Adelaide Fernandes and Aguilar-Pimentel, {Juan Antonio} and {de Angelis}, {Martin Hrabe} and Guedes, {Joana Ribeiro} and Brito, {Maria Alexandra} and Saida Ortolano and Giovambattista Pani and Sophia Athanasopoulou and Gonos, {Efstathios S.} and Markus Schosserer and Johannes Grillari and Part Peterson and Tuna, {Bilge Guvenc} and Soner Dogan and Angelika Meyer and {van Os}, Ronald and Anne-Ulrike Trendelenburg",
note = "Copyright {\textcopyright} 2018 The Authors. Published by Elsevier B.V. All rights reserved.",
year = "2018",
month = nov,
doi = "10.1016/j.arr.2018.07.004",
language = "English",
volume = "47",
pages = "214--277",
journal = "Ageing Research Reviews",
issn = "1568-1637",
publisher = "ELSEVIER IRELAND LTD",

}

RIS

TY - JOUR

T1 - Towards frailty biomarkers

T2 - Candidates from genes and pathways regulated in aging and age-related diseases

AU - Cardoso, Ana Luisa

AU - Fernandes, Adelaide

AU - Aguilar-Pimentel, Juan Antonio

AU - de Angelis, Martin Hrabe

AU - Guedes, Joana Ribeiro

AU - Brito, Maria Alexandra

AU - Ortolano, Saida

AU - Pani, Giovambattista

AU - Athanasopoulou, Sophia

AU - Gonos, Efstathios S.

AU - Schosserer, Markus

AU - Grillari, Johannes

AU - Peterson, Part

AU - Tuna, Bilge Guvenc

AU - Dogan, Soner

AU - Meyer, Angelika

AU - van Os, Ronald

AU - Trendelenburg, Anne-Ulrike

N1 - Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2018/11

Y1 - 2018/11

N2 - Objective: Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel.Methods: Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers.Results: A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified.Conclusion: Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) CXCL10 (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), CX3CL1 (C-X3-C motif chemokine ligand 1), (2) GDF15 (growth differentiation factor 15), FNDC5 (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) PLAU (plasminogen activator, urokinase), AGT (angiotensinogen), (5) BDNF (brain derived neurotrophic factor), progranulin (PGRN), (6) alpha-klotho (KL), FGF23 (fibroblast growth factor 23), FGF21, leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), AHCY (adenosylhomocysteinase) and KRT18 (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin alpha, (2) APP (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) S100B (S100 calcium binding protein B), (4) TGF beta (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), TGM2 (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), HMGB1 (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (REIN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.

AB - Objective: Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel.Methods: Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers.Results: A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified.Conclusion: Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) CXCL10 (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), CX3CL1 (C-X3-C motif chemokine ligand 1), (2) GDF15 (growth differentiation factor 15), FNDC5 (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) PLAU (plasminogen activator, urokinase), AGT (angiotensinogen), (5) BDNF (brain derived neurotrophic factor), progranulin (PGRN), (6) alpha-klotho (KL), FGF23 (fibroblast growth factor 23), FGF21, leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), AHCY (adenosylhomocysteinase) and KRT18 (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin alpha, (2) APP (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) S100B (S100 calcium binding protein B), (4) TGF beta (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), TGM2 (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), HMGB1 (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (REIN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.

KW - Frailty

KW - Biomarker panel

KW - Hallmark of aging pathways

KW - Age-related diseases

KW - GROWTH-FACTOR 21

KW - GLYCATION END-PRODUCTS

KW - DIFFERENTIATION FACTOR 15

KW - TERMINAL-AGRIN FRAGMENT

KW - CHRONIC KIDNEY-DISEASE

KW - NF-KAPPA-B

KW - PLASMINOGEN-ACTIVATOR INHIBITOR-1

KW - MILD COGNITIVE IMPAIRMENT

KW - FATTY LIVER-DISEASE

KW - CHRONIC HEART-FAILURE

U2 - 10.1016/j.arr.2018.07.004

DO - 10.1016/j.arr.2018.07.004

M3 - Review article

C2 - 30071357

VL - 47

SP - 214

EP - 277

JO - Ageing Research Reviews

JF - Ageing Research Reviews

SN - 1568-1637

ER -

ID: 64746843