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

Abstract

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) α-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 α, (2) APP (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) S100B (S100 calcium binding protein B), (4) TGFβ (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.

Aging Skeletal Muscle Proteomics Finds Changes in Spliceosome, Immune factors, Proteostasis and Mitochondria

“…Of note, calreticulin is used by macrophages to tag cells to be removed by programmed cell phagocytosis 66 . Consistent with this finding, CALR is considered a main biomarker of age-related diseases and frailty 67 .…”

Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches

“…The various SASP components, such as inflammatory molecules (cytokines and chemokines, extracellular damage‐associated alarmin high‐mobility group box 1 [HMGB1] protein), growth factors and regulators (transforming growth factor beta [TGFβ], insulin‐like growth factor‐binding proteins [IGFBPs]), extracellular proteinases and their inhibitors (matrix metalloproteinases [MMPs], tissue inhibitors of metalloproteinases [TIMPs], plasminogen activator inhibitor‐1 [PAI‐1]) are among candidate biomarkers of aging. [ 37,47 ] Monitoring SASP factors can constitute a promising and feasible approach for the evaluation of general tissue or cell culture senescence status [ 48 ] ; however, the profile of secreted proteins may vary significantly depending on cell type and stage of senescence, [ 37,49 ] complicating the determination of optimal threshold values for all types of cells.…”

Better be prepared

“…The latter might explain the lack of uniformity between the respondents using these type of tests in their preoperative physical fitness assessment. Moreover, besides measuring cardiorespiratory fitness, it is important to preoperatively assess muscle strength and functional mobility, as these components of physical fitness are a prerequisite for (early) mobilization and being physically active postoperatively [42].…”

“…Besides the pathophysiology of cancer cachexia, disease symptoms and anti-tumor therapies (e.g., chemo-, radio-, immunotherapy) hamper adequate food-intake (e.g., vomiting, nausea, early satiety). This influences the clinical course of the disease, the patient's physical performance, and the patient's quality of life, especially in frail elderly [39,40,42]. Frailty can be defined as a diminished adaptive capacity and increased vulnerability to cope with events (e.g., surgery, chemoradiation, hospitalization), that are stressors for the physiological system [38,43].…”

“…In There is an increasing emergence in the demand for making research relevant to patients and the wider public, thereby reducing research waste [40,41]. The embedded scientist approach allows for co-production (e.g., new forms of knowledge, values, and social relations) between patients and their support system, health care professionals, and researchers with the aim to narrow the gap between research and clinical practice [31,42]. One might debate about its methodological quality when compared to the traditional randomized controlled trial (RCT) for Therefore, a collaborative interdisciplinary approach is advocated to initiate and guide the transition and making research relevant to patients, the care system, and a wider public.…”