PMID- 30071357
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20211204
IS  - 1872-9649 (Electronic)
IS  - 1568-1637 (Linking)
VI  - 47
DP  - 2018 Nov
TI  - Towards frailty biomarkers: Candidates from genes and pathways regulated in aging 
      and age-related diseases.
PG  - 214-277
LID - S1568-1637(18)30093-X [pii]
LID - 10.1016/j.arr.2018.07.004 [doi]
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) TGFbeta 
      (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 (RETN), 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.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Cardoso, Ana Luisa
AU  - Cardoso AL
AD  - Center for Neurosciences, Cell Biology, Faculty of Medicine - Polo I, University 
      of Coimbra, Coimbra, Portugal.
FAU - Fernandes, Adelaide
AU  - Fernandes A
AD  - iMed.ULisboa, Research Institute for Medicines, Department of Biochemistry and 
      Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal.
FAU - Aguilar-Pimentel, Juan Antonio
AU  - Aguilar-Pimentel JA
AD  - German Mouse Clinic, Institute for Experimental Genetics, Helmholtz Zentrum 
      Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
FAU - de Angelis, Martin Hrabe
AU  - de Angelis MH
AD  - German Mouse Clinic, Institute for Experimental Genetics, Helmholtz Zentrum 
      Muenchen, German Research Center for Environmental Health and German Center for 
      Diabetes Research (DZD), Chair of Experimental Genetics, School of Life Science 
      Weihenstephan, Technische University Munich, Neuherberg, Germany.
FAU - Guedes, Joana Ribeiro
AU  - Guedes JR
AD  - Center for Neurosciences, Cell Biology, Faculty of Medicine - Polo I, University 
      of Coimbra, Coimbra, Portugal.
FAU - Brito, Maria Alexandra
AU  - Brito MA
AD  - iMed.ULisboa, Research Institute for Medicines, Department of Biochemistry and 
      Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal.
FAU - Ortolano, Saida
AU  - Ortolano S
AD  - Rare Diseases and Pediatric Medicine Research Group, Galicia Sur Health Research 
      Institute-SERGAS-UVIGO, Vigo, Spain.
FAU - Pani, Giovambattista
AU  - Pani G
AD  - Insititute of General Pathology, Universita Cattolica del Sacro Cuore, Faculty of 
      Medicine, Rome, Italy.
FAU - Athanasopoulou, Sophia
AU  - Athanasopoulou S
AD  - Molecular and Cellular Aging Laboratory, Institute of Biology, Medicinal 
      Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, 
      Greece.
FAU - Gonos, Efstathios S
AU  - Gonos ES
AD  - Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic 
      Research Foundation, Athens, Greece.
FAU - Schosserer, Markus
AU  - Schosserer M
AD  - Department of Biotechnology, University of Natural Resources and Life Sciences, 
      Vienna, Austria.
FAU - Grillari, Johannes
AU  - Grillari J
AD  - Christian Doppler Laboratory on Biotechnology of Skin Aging, Department of 
      Biotechnology, University of Natural Resources and Life Sciences, Vienna, 
      Austria.
FAU - Peterson, Part
AU  - Peterson P
AD  - Institute of Biomedicine and Translational Medicine, University of Tartu, 
      Estonia.
FAU - Tuna, Bilge Guvenc
AU  - Tuna BG
AD  - School of Medicine, Yeditepe University, Istanbul, Turkey.
FAU - Dogan, Soner
AU  - Dogan S
AD  - Department of Medical Biology, School of Medicine, Yeditepe University, Istanbul, 
      Turkey.
FAU - Meyer, Angelika
AU  - Meyer A
AD  - Novartis Institutes for Biomedical Research, Musculoskeletal Disease Area, Muscle 
      Research, Basel, Switzerland.
FAU - van Os, Ronald
AU  - van Os R
AD  - Central Animal Facility, Mouse Clinic for Cancer and Aging, University Medical 
      Center Groningen, University of Groningen, Groningen, The Netherlands.
FAU - Trendelenburg, Anne-Ulrike
AU  - Trendelenburg AU
AD  - Novartis Institutes for Biomedical Research, Musculoskeletal Disease Area, Muscle 
      Research, Cambridge, USA. Electronic address: 
      anne-ulrike.trendelenburg@novartis.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180730
PL  - England
TA  - Ageing Res Rev
JT  - Ageing research reviews
JID - 101128963
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Biomarkers)
RN  - 0 (FGF23 protein, human)
RN  - 0 (FNDC5 protein, human)
RN  - 0 (Fgf23 protein, mouse)
RN  - 0 (Fibronectins)
RN  - 0 (GDF15 protein, human)
RN  - 0 (Growth Differentiation Factor 15)
RN  - 0 (IGF1 protein, human)
RN  - 0 (IL1RL1 protein, human)
RN  - 0 (Interleukin-1 Receptor-Like 1 Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (MicroRNAs)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 7Q7P4S7RRE (Fibroblast Growth Factor-23)
MH  - Aged
MH  - Aging/genetics/*metabolism
MH  - Amyloid beta-Peptides/genetics
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Apoptosis/physiology
MH  - Biomarkers/metabolism
MH  - Fibroblast Growth Factor-23
MH  - Fibronectins/genetics/metabolism
MH  - Frailty/genetics/*metabolism
MH  - Genetic Association Studies/*methods/trends
MH  - Growth Differentiation Factor 15/genetics/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Interleukin-1 Receptor-Like 1 Protein/genetics/metabolism
MH  - Membrane Glycoproteins/genetics/metabolism
MH  - MicroRNAs/genetics/metabolism
MH  - Signal Transduction/*physiology
OTO - NOTNLM
OT  - *Age-related diseases
OT  - *Biomarker panel
OT  - *Frailty
OT  - *Hallmark of aging pathways
EDAT- 2018/08/03 06:00
MHDA- 2019/08/06 06:00
CRDT- 2018/08/03 06:00
PHST- 2018/04/06 00:00 [received]
PHST- 2018/07/08 00:00 [revised]
PHST- 2018/07/10 00:00 [accepted]
PHST- 2018/08/03 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2018/08/03 06:00 [entrez]
AID - S1568-1637(18)30093-X [pii]
AID - 10.1016/j.arr.2018.07.004 [doi]
PST - ppublish
SO  - Ageing Res Rev. 2018 Nov;47:214-277. doi: 10.1016/j.arr.2018.07.004. Epub 2018 
      Jul 30.