PMID- 37080342
OWN - NLM
STAT- MEDLINE
DCOM- 20230524
LR  - 20230524
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 177
DP  - 2023 Jun 15
TI  - Correlations between biomarkers of senescent cell accumulation at the systemic, 
      tissue and cellular levels in elderly patients.
PG  - 112176
LID - S0531-5565(23)00097-9 [pii]
LID - 10.1016/j.exger.2023.112176 [doi]
AB  - The aim of the study was to investigate the relationship between established 
      clinical systemic biomarkers of ageing and the development of age-associated 
      diseases and senescent cell biomarkers at tissue and cellular levels. 
      Thirty-eight patients (mean age 70 +/- 4.9 years) who were assessed for traditional 
      risk factors for cardiovascular diseases were included. From all patients we 
      obtained biomaterials (peripheral blood, skin, subcutaneous fatty tissue) and 
      isolated different cell types (peripheral blood mononuclear cells (PBMC), 
      fibroblasts (FB) and mesenchymal stem/stromal cells (MSC)). Isolated cells were 
      analyzed using several senescent cells biomarkers such as telomere length and 
      telomerase activity, proliferation rate, cell cycle inhibitor expression (p16 and 
      p21), b-galactosidase activity, gH2AX expression. CD34+ cell content in 
      peripheral blood was determined by flow cytometry. Systemic senescent 
      cell-associated factors (insulin-like growth factor 1 (IGF-1), fibroblast growth 
      factor 21 (FGF-21), osteoprogerin, ferritin, soluble vascular cell adhesion 
      molecule (VCAM-1), intercellular adhesion molecule 1 (ICAM-1)) in peripheral 
      blood as well as senescence-associated secretory phenotype (SASP) components in 
      MSC and FB secretome were evaluated by ELISA. Skin and adipose tissue biopsy 
      samples were analyzed histologically to assess senescent cell markers. A strong 
      significant association of tissue p16 expression with age (r = 0.600, p < 0.001), 
      pulse wave velocity (PWV) (r = 0.394, p = 0.015), vascular cell adhesion molecule 
      (VCAM-1) content (r = 0.312, p = 0.006) in the systemic blood stream and p16 mRNA 
      level in the blood mononuclear cells (MNCs) (r = 0.380, p = 0.046) were confirmed 
      by correlation analysis. Statistically significant correlations were found with 
      indicators of FBs and MSCs proliferation in culture and acquisition of SASP by 
      the cells. Thus, p16 expression in tissues correlated significantly with 
      interleukin-6 (IL-6) (r = 0.485, p < 0.05) and monocyte chemoattractant protein 
      type 1 (MCP-1) (r = 0.372, p < 0.05) secretion by isolated cells. The results of 
      regression analysis confirmed that, regardless of age, the expression of p16 was 
      associated with the proliferation of isolated cells and IL-6 within SASP. Based 
      on these findings, two models have been proposed to predict the level of p16 
      expression in tissues from the levels of other markers of senescent cell 
      accumulation determined by non-invasive methods and available in clinical 
      practice.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Sorokina, Anna Grigorevna
AU  - Sorokina AG
AD  - Lomonosov Moscow State University, Medical Research and Education Centre, 
      Age-associated Diseases Department, Moscow, Russian Federation. Electronic 
      address: ASorokina@mc.msu.ru.
FAU - Orlova, Yana Arturovna
AU  - Orlova YA
AD  - Lomonosov Moscow State University, Medical Research and Education Centre, 
      Age-associated Diseases Department, Moscow, Russian Federation; Lomonosov Moscow 
      State University, Faculty of Medicine, Moscow, Russian Federation.
FAU - Grigorieva, Olga Aleksandrovna
AU  - Grigorieva OA
AD  - Lomonosov Moscow State University, Medical Research and Education Center, 
      Institute for Regenerative Medicine, Tissue Repair and Regeneration Laboratory, 
      Moscow, Russian Federation.
FAU - Novoseletskaya, Ekaterina Sergeevna
AU  - Novoseletskaya ES
AD  - Lomonosov Moscow State University, Medical Research and Education Center, 
      Institute for Regenerative Medicine, Tissue Repair and Regeneration Laboratory, 
      Moscow, Russian Federation.
FAU - Basalova, Nataliya Andreevna
AU  - Basalova NA
AD  - Lomonosov Moscow State University, Medical Research and Education Center, 
      Institute for Regenerative Medicine, Tissue Repair and Regeneration Laboratory, 
      Moscow, Russian Federation; Lomonosov Moscow State University, Faculty of 
      Medicine, Department of Biochemistry and Regenerative Biomedicine, Moscow, 
      Russian Federation.
FAU - Alexandrushkina, Natalya Andreevna
AU  - Alexandrushkina NA
AD  - Lomonosov Moscow State University, Faculty of Medicine, Department of 
      Biochemistry and Regenerative Biomedicine, Moscow, Russian Federation; Lomonosov 
      Moscow State University, Medical Research and Education Centre, Institute for 
      Regenerative Medicine, Laboratory of Gene-cell Therapy, Moscow, Russian 
      Federation.
FAU - Vigovskiy, Maksim Aleksandrovich
AU  - Vigovskiy MA
AD  - Lomonosov Moscow State University, Medical Research and Education Center, 
      Institute for Regenerative Medicine, Tissue Repair and Regeneration Laboratory, 
      Moscow, Russian Federation; Lomonosov Moscow State University, Faculty of 
      Medicine, Department of Biochemistry and Regenerative Biomedicine, Moscow, 
      Russian Federation.
FAU - Kirillova, Karina Igorevna
AU  - Kirillova KI
AD  - Lomonosov Moscow State University, Medical Research and Education Centre, 
      Laboratory Diagnostics Department, Moscow, Russian Federation.
FAU - Balatsky, Alexander Vladimirovich
AU  - Balatsky AV
AD  - Lomonosov Moscow State University, Medical Research and Education Centre, 
      Laboratory Diagnostics Department, Moscow, Russian Federation.
FAU - Samokhodskaya, Larisa Mihailovna
AU  - Samokhodskaya LM
AD  - Lomonosov Moscow State University, Faculty of Medicine, Moscow, Russian 
      Federation; Lomonosov Moscow State University, Medical Research and Education 
      Centre, Laboratory Diagnostics Department, Moscow, Russian Federation; Lomonosov 
      Moscow State University, Medical Research and Education Centre, Moscow, Russian 
      Federation.
FAU - Danilova, Natalya Vladimirovna
AU  - Danilova NV
AD  - Lomonosov Moscow State University, Medical Research and Education Centre, 
      Department of Clinical Pathology, Moscow, Russian Federation; Lomonosov Moscow 
      State University, Faculty of Medicine, Department of Physiology and General 
      Pathology, Moscow, Russian Federation.
FAU - Dyachkova, Uliana Denisovna
AU  - Dyachkova UD
AD  - Lomonosov Moscow State University, Faculty of Medicine, Moscow, Russian 
      Federation.
FAU - Kakotkin, Victor Victorovich
AU  - Kakotkin VV
AD  - Lomonosov Moscow State University, Faculty of Medicine, Department of General and 
      Specialized Surgery, Moscow, Russian Federation.
FAU - Asratyan, David Albertovich
AU  - Asratyan DA
AD  - Lomonosov Moscow State University, Medical Research and Education Centre, Moscow, 
      Russian Federation.
FAU - Akopyan, Zhanna Alekseevna
AU  - Akopyan ZA
AD  - Lomonosov Moscow State University, Faculty of Medicine, Department of Clinical 
      Modeling and Manual Skills, Moscow, Russian Federation.
FAU - Efimenko, Anastasia Yurievna
AU  - Efimenko AY
AD  - Lomonosov Moscow State University, Medical Research and Education Center, 
      Institute for Regenerative Medicine, Tissue Repair and Regeneration Laboratory, 
      Moscow, Russian Federation; Lomonosov Moscow State University, Faculty of 
      Medicine, Department of Biochemistry and Regenerative Biomedicine, Moscow, 
      Russian Federation.
LA  - eng
PT  - Journal Article
DEP - 20230424
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Biomarkers)
SB  - IM
MH  - *Cellular Senescence/genetics
MH  - *Vascular Cell Adhesion Molecule-1
MH  - Leukocytes, Mononuclear/metabolism
MH  - Interleukin-6
MH  - Pulse Wave Analysis
MH  - Biomarkers/metabolism
MH  - Cells, Cultured
OTO - NOTNLM
OT  - Ageing
OT  - Biomarker
OT  - PWV
OT  - Senescence cell
OT  - p16INK
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2023/04/21 00:42
MHDA- 2023/05/24 06:42
CRDT- 2023/04/20 19:24
PHST- 2023/01/21 00:00 [received]
PHST- 2023/04/13 00:00 [revised]
PHST- 2023/04/14 00:00 [accepted]
PHST- 2023/05/24 06:42 [medline]
PHST- 2023/04/21 00:42 [pubmed]
PHST- 2023/04/20 19:24 [entrez]
AID - S0531-5565(23)00097-9 [pii]
AID - 10.1016/j.exger.2023.112176 [doi]
PST - ppublish
SO  - Exp Gerontol. 2023 Jun 15;177:112176. doi: 10.1016/j.exger.2023.112176. Epub 2023 
      Apr 24.