Biological Aging and Venous Thromboembolism: A Review of Telomeres and Beyond

Overview

Journal Biomedicines

Date 2025 Jan 25

PMID 39857599

Authors

Rafaela Vostatek

Cihan Ay

Affiliations

Soon will be listed here.

Abstract

Although venous thromboembolism (VTE) is the third most common cardiovascular disease, and the risk of VTE increases sharply with advancing age, approximately 40% of VTE cases are currently classified as unprovoked, highlighting the importance of risk factor research. While chronological aging is associated with the risk of VTE, the association with biological aging remains unclear. Biological aging is highly complex, influenced by several dysregulated cellular and biochemical mechanisms. In the last decade, advancements in omics methodologies provided insights into the molecular complexity of biological aging. Techniques such as high-throughput genomics, epigenomics, transcriptomics, proteomics, and metabolomics analyses identified and quantified numerous epigenetic markers, transcripts, proteins, and metabolites. These methods have also revealed the molecular alterations organisms undergo as they age. Despite the progress, there is still a lack of consensus regarding the methods for assessing and validating these biomarkers, and their application lacks standardization. This review gives an overview of biomarkers of biological aging, including telomere length, and their potential role for VTE. Furthermore, we critically examine the advantages and disadvantages of the proposed methods and discuss possible future directions for investigating biological aging in VTE.

References

Vaiserman A, Krasnienkov D . Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives. Front Genet. 2021; 11:630186. PMC: 7859450. DOI: 10.3389/fgene.2020.630186. View

Nguyen D, Jeon H, Lee J . Tissue factor links inflammation, thrombosis, and senescence in COVID-19. Sci Rep. 2022; 12(1):19842. PMC: 9673213. DOI: 10.1038/s41598-022-23950-y. View

Mari D, Ogliari G, Castaldi D, Vitale G, Bollini E, Lio D . Hemostasis and ageing. Immun Ageing. 2008; 5:12. PMC: 2602988. DOI: 10.1186/1742-4933-5-12. View

Aissi D, Dennis J, Ladouceur M, Truong V, Zwingerman N, Rocanin-Arjo A . Genome-wide investigation of DNA methylation marks associated with FV Leiden mutation. PLoS One. 2014; 9(9):e108087. PMC: 4179266. DOI: 10.1371/journal.pone.0108087. View

Herbig U, Jobling W, Chen B, Chen D, Sedivy J . Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004; 14(4):501-13. DOI: 10.1016/s1097-2765(04)00256-4. View

Versteeg H, Heemskerk J, Levi M, Reitsma P . New fundamentals in hemostasis. Physiol Rev. 2013; 93(1):327-58. DOI: 10.1152/physrev.00016.2011. View

Jain M, Rivera S, Monclus E, Synenki L, Zirk A, Eisenbart J . Mitochondrial reactive oxygen species regulate transforming growth factor-β signaling. J Biol Chem. 2012; 288(2):770-7. PMC: 3543026. DOI: 10.1074/jbc.M112.431973. View

Benincasa G, Costa D, Infante T, Lucchese R, Donatelli F, Napoli C . Interplay between genetics and epigenetics in modulating the risk of venous thromboembolism: A new challenge for personalized therapy. Thromb Res. 2019; 177:145-153. DOI: 10.1016/j.thromres.2019.03.008. View

Di Leonardo A, Linke S, Clarkin K, Wahl G . DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev. 1994; 8(21):2540-51. DOI: 10.1101/gad.8.21.2540. View

10.

Tracy R, Bovill E . Thrombosis and cardiovascular risk in the elderly. Arch Pathol Lab Med. 1992; 116(12):1307-12. View

11.

Schaum N, Lehallier B, Hahn O, Palovics R, Hosseinzadeh S, Lee S . Ageing hallmarks exhibit organ-specific temporal signatures. Nature. 2020; 583(7817):596-602. PMC: 7757734. DOI: 10.1038/s41586-020-2499-y. View

12.

Tanaka T, Basisty N, Fantoni G, Candia J, Moore A, Biancotto A . Plasma proteomic biomarker signature of age predicts health and life span. Elife. 2020; 9. PMC: 7723412. DOI: 10.7554/eLife.61073. View

13.

Wang Y, Fuller G . The putative role of fibrin fragments in the biosynthesis of fibrinogen by hepatoma cells. Biochem Biophys Res Commun. 1991; 175(2):562-7. DOI: 10.1016/0006-291x(91)91602-9. View

14.

Samani N, Boultby R, Butler R, Thompson J, Goodall A . Telomere shortening in atherosclerosis. Lancet. 2001; 358(9280):472-3. DOI: 10.1016/S0140-6736(01)05633-1. View

15.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

16.

Sanchez-Santos A, Martinez-Hernandez M, Contreras-Ramos A, Ortega-Camarillo C, Baiza-Gutman L . Hyperglycemia-induced mouse trophoblast spreading is mediated by reactive oxygen species. Mol Reprod Dev. 2018; 85(4):303-315. DOI: 10.1002/mrd.22965. View

17.

Tofler G, Massaro J, Levy D, Mittleman M, Sutherland P, Lipinska I . Relation of the prothrombotic state to increasing age (from the Framingham Offspring Study). Am J Cardiol. 2005; 96(9):1280-3. DOI: 10.1016/j.amjcard.2005.06.072. View

18.

Christiansen L, Lenart A, Tan Q, Vaupel J, Aviv A, McGue M . DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell. 2015; 15(1):149-54. PMC: 4717264. DOI: 10.1111/acel.12421. View

19.

Choi J, Lyons D, Kim M, Moore J, Zilberman D . DNA Methylation and Histone H1 Jointly Repress Transposable Elements and Aberrant Intragenic Transcripts. Mol Cell. 2019; 77(2):310-323.e7. DOI: 10.1016/j.molcel.2019.10.011. View

20.

Bruzelius M, Iglesias M, Hong M, Sanchez-Rivera L, Gyorgy B, Souto J . PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study. Blood. 2016; 128(23):e59-e66. DOI: 10.1182/blood-2016-05-711846. View