Comprehensive analysis of aging-related gene expression patterns and identification of potential intervention targets

被引:0
作者
Yang, Sha [1 ]
Song, Jianning [3 ]
Deng, Min [4 ]
Cheng, Si [2 ]
机构
[1] Guizhou Univ, Med Coll, Guiyang 550025, Guizhou, Peoples R China
[2] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing 400010, Peoples R China
[3] GuiQian Int Gen Hosp, Intervent Dept, Guiyang, Peoples R China
[4] Chongqing Med & Pharmaceut Coll, Affiliated Hosp 1, Chongqing 400000, Peoples R China
关键词
aging; biomarkers; Mendelian randomization; machine learning; mediators; MENDELIAN RANDOMIZATION; TELOMERE LENGTH;
D O I
10.1093/postmj/qgae131
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose This study aims to understand the molecular mechanisms underlying the aging process and identify potential interventions to mitigate age-related decline and diseases.Methods This study utilized the GSE168753 dataset to conduct comprehensive differential gene expression analysis and co-expression module analysis. Machine learning and Mendelian randomization analyses were employed to identify core aging-associated genes and potential drug targets. Molecular docking simulations and mediation analysis were also performed to explore potential compounds and mediators involved in the aging process.Results The analysis identified 4164 differentially expressed genes, with 1893 upregulated and 2271 downregulated genes. Co-expression analysis revealed 21 modules, including both positively and negatively correlated modules between older age and younger age groups. Further exploration identified 509 aging-related genes with distinct biological functions. Machine learning and Mendelian randomization analyses identified eight core genes associated with aging, including DPP9, GNAZ, and RELL2. Molecular docking simulations suggested resveratrol, folic acid, and ethinyl estradiol as potential compounds capable of attenuating aging through modulation of RELL2 expression. Mediation analysis indicated that eosinophil counts and neutrophil count might act as mediators in the causal relationship between genes and aging-related indicators.Conclusion This comprehensive study provides valuable insights into the molecular mechanisms of aging and offers important implications for the development of anti-aging therapeutics. Key Messages What is already known on this topic - Prior research outlines aging's complexity, necessitating precise molecular targets for intervention. What this study adds - This study identifies novel aging-related genes, potential drug targets, and therapeutic compounds, advancing our understanding of aging mechanisms. How this study might affect research, practice, or policy - Findings may inform targeted therapies for age-related conditions, influencing future research and clinical practices.Conclusion This comprehensive study provides valuable insights into the molecular mechanisms of aging and offers important implications for the development of anti-aging therapeutics. Key Messages What is already known on this topic - Prior research outlines aging's complexity, necessitating precise molecular targets for intervention. What this study adds - This study identifies novel aging-related genes, potential drug targets, and therapeutic compounds, advancing our understanding of aging mechanisms. How this study might affect research, practice, or policy - Findings may inform targeted therapies for age-related conditions, influencing future research and clinical practices.
引用
收藏
页码:219 / 231
页数:13
相关论文
共 57 条
  • [1] Impact of Folic Acid in Modulating Antioxidant Activity, Osmoprotectants, Anatomical Responses, and Photosynthetic Efficiency of Plectranthus amboinicus Under Salinity Conditions
    Al-Elwany, Omar A. A., I
    Hemida, Khaulood A.
    Abdel-Razek, Mohamed A.
    Abd El-Mageed, Taia A.
    El-Saadony, Mohamed T.
    AbuQamar, Synan F.
    El-Tarabily, Khaled A.
    Taha, Ragab S.
    [J]. FRONTIERS IN PLANT SCIENCE, 2022, 13
  • [2] Expression of long non-coding RNA ANRIL predicts a poor prognosis in intrahepatic cholangiocarcinoma
    Angenard, Gaelle
    Merdrignac, Aude
    Louis, Corentin
    Edeline, Julien
    Coulouarn, Cedric
    [J]. DIGESTIVE AND LIVER DISEASE, 2019, 51 (09) : 1337 - 1343
  • [3] [Anonymous], Nat Genet, V53, DOI [10.1038/s41588-021-00913-z, DOI 10.1038/S41588-021-00913-Z]
  • [4] Telomere length and frailty in older adults-A systematic review and meta-analysis
    Araujo Carvalho, Aline Carla
    Tavares Mendes, Mario Luis
    da Silva Reis, Monique Carla
    Santos, Victor Santana
    Tanajura, Diego Moura
    Saquete Martins-Filho, Paulo Ricardo
    [J]. AGEING RESEARCH REVIEWS, 2019, 54
  • [5] A genome-wide association study of the frailty index highlights brain pathways in ageing
    Atkins, Janice L.
    Jylhava, Juulia
    Pedersen, Nancy L.
    Magnusson, Patrik K.
    Lu, Yi
    Wang, Yunzhang
    Hagg, Sara
    Melzer, David
    Williams, Dylan M.
    Pilling, Luke C.
    [J]. AGING CELL, 2021, 20 (09)
  • [6] Whole-exome imputation within UK Biobank powers rare coding variant association and fine-mapping analyses
    Barton, Alison R.
    Sherman, Maxwell A.
    Mukamel, Ronen E.
    Loh, Po-Ru
    [J]. NATURE GENETICS, 2021, 53 (08) : 1260 - +
  • [7] Resveratrol and metabolic health in COPD: A proof-of-concept randomized controlled trial
    Beijers, Rosanne J. H. C. G.
    Gosker, Harry R.
    Sanders, Karin J. C.
    de Theije, Chiel
    Kelders, Marco
    Clarke, Gerard
    Cryan, John F.
    van den Borst, Bram
    Schols, Annemie M. W. J.
    [J]. CLINICAL NUTRITION, 2020, 39 (10) : 2989 - 2997
  • [8] Meta-analysis and Mendelian randomization: A review
    Bowden, Jack
    Holmes, Michael, V
    [J]. RESEARCH SYNTHESIS METHODS, 2019, 10 (04) : 486 - 496
  • [9] Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic
    Bowden, Jack
    Del Greco, Fabiola M.
    Minelli, Cosetta
    Smith, George Davey
    Sheehan, Nuala A.
    Thompson, John R.
    [J]. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2016, 45 (06) : 1961 - 1974
  • [10] Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator
    Bowden, Jack
    Smith, George Davey
    Haycock, Philip C.
    Burgess, Stephen
    [J]. GENETIC EPIDEMIOLOGY, 2016, 40 (04) : 304 - 314