Affiliation:
1. Medical Research and Educational Center, Lomonosov Moscow State University; Faculty of Fundamental Medicine, Lomonosov Moscow State University
2. Medical Research and Educational Center, Lomonosov Moscow State University
3. Russian Gerontology Research Center of Pirogov Russian National Research Medical University
4. Institute of Biomedical Problems of the Russian Academy of Sciences
5. Faculty of Fundamental Medicine, Lomonosov Moscow State University
Abstract
Aim To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated. Also, biomaterials (peripheral blood, skin, subcutaneous adipose tissue) were collected during the surgery and were used for isolation of several cell types and subsequent histological analysis to determine various markers of senescent cells.Results The study included 80 patients aged 65 to 90 years. The correlation analysis identified the most significant indexes that reflected the accumulation of senescent cells at the systemic, tissue, and cellular levels (r>0.3, р<0.05) and showed positive and negative correlations with PWV. The following blood plasma factors were selected as the markers of ageing: insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF-21), and vascular endothelium adhesion molecule 1 (VCAM-1). A significant negative correlation between PWV and IGF-1 concentration was found. Among the tissue markers, P16INK, the key marker for tissue accumulation of senescent cells, predictably showed a positive correlation (r=0.394, p<0.05). A medium-strength correlation with parameters of the 96-h increment of mesenchymal stromal cells and fibroblasts and a weak correlation with IL-6 as a SASP (specific senescent-associated secretory phenotype) were noted. Results of the multifactorial linear regression analysis showed that the blood plasma marker, VCAM-1, and the cell marker, 96-h increment of fibroblasts, were associated with PWV regardless of the patient’s age.Conclusion Stiffness of great arteries as measured by PWV significantly correlates with a number of plasma, tissue, and cellular markers for accumulation of senescent cells. This fact suggests PWV as a candidate for inclusion in the panel of parameters for evaluation and monitoring of the biological age during the senolytic therapy.
Publisher
APO Society of Specialists in Heart Failure
Subject
Cardiology and Cardiovascular Medicine
Reference38 articles.
1. St Sauver JL, Boyd CM, Grossardt BR, Bobo WV, Finney Rutten LJ, Roger VL et al. Risk of developing multimorbidity across all ages in an historical cohort study: differences by sex and ethnicity. BMJ Open. 2015;5(2):e006413. DOI: 10.1136/bmjopen-2014-006413
2. Kirkland JL. Translating the Science of Aging into Therapeutic Interventions. Cold Spring Harbor Perspectives in Medicine. 2016;6(3):a025908. DOI: 10.1101/cshperspect.a025908
3. Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. Journal of Internal Medicine. 2020;288(5):518–36. DOI: 10.1111/joim.13141
4. World Health Organization. A global brief of hypertension. Silent killer, global public health crisis: World Health Day 2013. 2013. [Av. at: https://www.who.int/publications/i/item/a-global-brief-on-hypertension-silent-killer-global-public-health-crisis-world-health-day-2013]
5. Özcan S, Alessio N, Acar MB, Mert E, Omerli F, Peluso G et al. Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses. Aging. 2016;8(7):1316–29. DOI: 10.18632/aging.100971
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献