|
|
衰老的生物标志物研究进展
|
Abstract:
衰老是一个复杂且多方面的过程，其通常被认为是生命过程中各种事件和过程所带来影响的积累过程，并将导致机体功能减退、慢性疾病，最终指向死亡。衰老的生物学研究本质在于回答三个核心问题：我们有多老？我们为什么会衰老？如何延缓衰老？而作为可被定量的生物参数，衰老的生物标志物可以衡量衰老的进程，进而帮助我们探究衰老的相关机制，最终做到干预衰老。本综述总结了衰老生物标志物研究的最新进展，从细胞、器官层面上回顾了衰老标志物的特征及它们在衰老过程中的作用机制，并讨论了利用这些标志物来开发衰老干预策略的潜力，揭示了未来衰老研究的方向及所面临的挑战。
Aging is a complex and multifaceted process characterized by the cumulative effects of various biological events and processes throughout the life course, ultimately resulting in diminished physiological function, chronic diseases, and eventually death. The core of biological research on aging revolves around three fundamental questions: How do we quantify age? What are the mechanisms driving aging? How can we delay or mitigate the aging process? Biomarkers of aging, as quantifiable biological parameters, provide a means to measure and understand the aging process, thereby facilitating the exploration of underlying mechanisms and enabling potential interventions. This review synthesizes recent advancements in the study of aging biomarkers, examines the characteristics and mechanisms of these markers at both cellular and organ levels, evaluates their potential for developing intervention strategies, and outlines future directions and challenges in aging research.
| [1] | López-Otín, C., Blasco, M.A., Partridge, L., Serrano, M. and Kroemer, G. (2023) Hallmarks of Aging: An Expanding Universe. Cell, 186, 243-278. https://doi.org/10.1016/j.cell.2022.11.001 |
| [2] | Kennedy, B.K., Berger, S.L., Brunet, A., Campisi, J., Cuervo, A.M., Epel, E.S., et al. (2014) Geroscience: Linking Aging to Chronic Disease. Cell, 159, 709-713. https://doi.org/10.1016/j.cell.2014.10.039 |
| [3] | Baker, G.T. and Sprott, R.L. (1988) Biomarkers of Aging. Experimental Gerontology, 23, 223-239. https://doi.org/10.1016/0531-5565(88)90025-3 |
| [4] | Rutledge, J., Oh, H. and Wyss-Coray, T. (2022) Measuring Biological Age Using Omics Data. Nature Reviews Genetics, 23, 715-727. https://doi.org/10.1038/s41576-022-00511-7 |
| [5] | Wagner, K., Cameron-Smith, D., Wessner, B. and Franzke, B. (2016) Biomarkers of Aging: From Function to Molecular Biology. Nutrients, 8, Article No. 338. https://doi.org/10.3390/nu8060338 |
| [6] | Bao, H., Cao, J., Chen, M., Chen, M., Chen, W., Chen, X., et al. (2023) Biomarkers of Aging. Science China Life Sciences, 66, 893-1066. https://doi.org/10.1007/s11427-023-2305-0 |
| [7] | Moqri, M., Herzog, C., Poganik, J.R., Justice, J., Belsky, D.W., Higgins-Chen, A., et al. (2023) Biomarkers of Aging for the Identification and Evaluation of Longevity Interventions. Cell, 186, 3758-3775. https://doi.org/10.1016/j.cell.2023.08.003 |
| [8] | Beausejour, C.M. (2003) Reversal of Human Cellular Senescence: Roles of the P53 and P16 Pathways. The EMBO Journal, 22, 4212-4222. https://doi.org/10.1093/emboj/cdg417 |
| [9] | Shay, J. (1991) A Role for Both RB and P53 in the Regulation of Human Cellular Senescence. Experimental Cell Research, 196, 33-39. https://doi.org/10.1016/0014-4827(91)90453-2 |
| [10] | Salama, R., Sadaie, M., Hoare, M. and Narita, M. (2014) Cellular Senescence and Its Effector Programs. Genes & Development, 28, 99-114. https://doi.org/10.1101/gad.235184.113 |
| [11] | Hernandez-Segura, A., Nehme, J. and Demaria, M. (2018) Hallmarks of Cellular Senescence. Trends in Cell Biology, 28, 436-453. https://doi.org/10.1016/j.tcb.2018.02.001 |
| [12] | Takasugi, M., Okada, R., Takahashi, A., Virya Chen, D., Watanabe, S. and Hara, E. (2017) Small Extracellular Vesicles Secreted from Senescent Cells Promote Cancer Cell Proliferation through Epha2. Nature Communications, 8, Article No. 15729. https://doi.org/10.1038/ncomms15728 |
| [13] | Fafián-Labora, J.A., Rodríguez-Navarro, J.A. and O’Loghlen, A. (2020) Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage. Cell Metabolism, 32, 71-86.e5. https://doi.org/10.1016/j.cmet.2020.06.004 |
| [14] | Acosta, J.C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J.P., et al. (2013) A Complex Secretory Program Orchestrated by the Inflammasome Controls Paracrine Senescence. Nature Cell Biology, 15, 978-990. https://doi.org/10.1038/ncb2784 |
| [15] | Jaenisch, R. and Bird, A. (2003) Epigenetic Regulation of Gene Expression: How the Genome Integrates Intrinsic and Environmental Signals. Nature Genetics, 33, 245-254. https://doi.org/10.1038/ng1089 |
| [16] | Jung, M. and Pfeifer, G.P. (2015) Aging and DNA Methylation. BMC Biology, 13, Article No. 7. https://doi.org/10.1186/s12915-015-0118-4 |
| [17] | Hannum, G., Guinney, J., Zhao, L., Zhang, L., Hughes, G., Sadda, S., et al. (2013) Genome-Wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Molecular Cell, 49, 359-367. https://doi.org/10.1016/j.molcel.2012.10.016 |
| [18] | Horvath, S. (2015) Erratum to: DNA Methylation Age of Human Tissues and Cell Types. Genome Biology, 16, Article No. 96. https://doi.org/10.1186/s13059-015-0649-6 |
| [19] | Han, S., Schroeder, E.A., Silva-García, C.G., Hebestreit, K., Mair, W.B. and Brunet, A. (2017) Mono-Unsaturated Fatty Acids Link H3k4me3 Modifiers to C. elegans Lifespan. Nature, 544, 185-190. https://doi.org/10.1038/nature21686 |
| [20] | Cao, Q., Wang, W., Williams, J.B., Yang, F., Wang, Z. and Yan, Z. (2020) Targeting Histone K4 Trimethylation for Treatment of Cognitive and Synaptic Deficits in Mouse Models of Alzheimer’s Disease. Science Advances, 6, eabc8096. https://doi.org/10.1126/sciadv.abc8096 |
| [21] | Bell, O., Burton, A., Dean, C., Gasser, S.M. and Torres-Padilla, M. (2023) Heterochromatin Definition and Function. Nature Reviews Molecular Cell Biology, 24, 691-694. https://doi.org/10.1038/s41580-023-00599-7 |
| [22] | Lee, J., Demarest, T.G., Babbar, M., Kim, E.W., Okur, M.N., De, S., et al. (2019) Cockayne Syndrome Group B Deficiency Reduces H3k9me3 Chromatin Remodeler SETDB1 and Exacerbates Cellular Aging. Nucleic Acids Research, 47, 8548-8562. https://doi.org/10.1093/nar/gkz568 |
| [23] | Zhang, B., Long, Q., Wu, S., Xu, Q., Song, S., Han, L., et al. (2024) Retraction Note: KDM4 Orchestrates Epigenomic Remodeling of Senescent Cells and Potentiates the Senescence-Associated Secretory Phenotype. Nature Aging, 4, 1898-1898. https://doi.org/10.1038/s43587-024-00749-2 |
| [24] | Abuetabh, Y., Wu, H.H., Chai, C., Al Yousef, H., Persad, S., Sergi, C.M., et al. (2022) DNA Damage Response Revisited: The P53 Family and Its Regulators Provide Endless Cancer Therapy Opportunities. Experimental & Molecular Medicine, 54, 1658-1669. https://doi.org/10.1038/s12276-022-00863-4 |
| [25] | Rodier, F. and Campisi, J. (2011) Four Faces of Cellular Senescence. Journal of Cell Biology, 192, 547-556. https://doi.org/10.1083/jcb.201009094 |
| [26] | Fraga, C.G., Shigenaga, M.K., Park, J.W., Degan, P. and Ames, B.N. (1990) Oxidative Damage to DNA during Aging: 8-Hydroxy-2’-Deoxyguanosine in Rat Organ DNA and Urine. Proceedings of the National Academy of Sciences, 87, 4533-4537. https://doi.org/10.1073/pnas.87.12.4533 |
| [27] | Cusanelli, E., Romero, C.A.P. and Chartrand, P. (2013) Telomeric Noncoding RNA TERRA Is Induced by Telomere Shortening to Nucleate Telomerase Molecules at Short Telomeres. Molecular Cell, 51, 780-791. https://doi.org/10.1016/j.molcel.2013.08.029 |
| [28] | Xu, M., Senanayaka, D., Zhao, R., Chigumira, T., Tripathi, A., Tones, J., et al. (2024) TERRA-LSD1 Phase Separation Promotes R-Loop Formation for Telomere Maintenance in ALT Cancer Cells. Nature Communications, 15, Article No. 2165. https://doi.org/10.1038/s41467-024-46509-z |
| [29] | Kokoszka, J.E., Coskun, P., Esposito, L.A. and Wallace, D.C. (2001) Increased Mitochondrial Oxidative Stress in the SoD2 (+/−) Mouse Results in the Age-Related Decline of Mitochondrial Function Culminating in Increased Apoptosis. Proceedings of the National Academy of Sciences, 98, 2278-2283. https://doi.org/10.1073/pnas.051627098 |
| [30] | Herbst, A., Pak, J.W., McKenzie, D., Bua, E., Bassiouni, M. and Aiken, J.M. (2007) Accumulation of Mitochondrial DNA Deletion Mutations in Aged Muscle Fibers: Evidence for a Causal Role in Muscle Fiber Loss. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62, 235-245. https://doi.org/10.1093/gerona/62.3.235 |
| [31] | Victorelli, S., Salmonowicz, H., Chapman, J., Martini, H., Vizioli, M.G., Riley, J.S., et al. (2023) Apoptotic Stress Causes MtDNA Release during Senescence and Drives the SASP. Nature, 622, 627-636. https://doi.org/10.1038/s41586-023-06621-4 |
| [32] | Dikic, I. (2017) Proteasomal and Autophagic Degradation Systems. Annual Review of Biochemistry, 86, 193-224. https://doi.org/10.1146/annurev-biochem-061516-044908 |
| [33] | Chen, L. and Feany, M.B. (2005) Α-synuclein Phosphorylation Controls Neurotoxicity and Inclusion Formation in a Drosophila Model of Parkinson Disease. Nature Neuroscience, 8, 657-663. https://doi.org/10.1038/nn1443 |
| [34] | Meng, J., Lv, Z., Qiao, X., Li, X., Li, Y., Zhang, Y., et al. (2017) The Decay of Redox-Stress Response Capacity Is a Substantive Characteristic of Aging: Revising the Redox Theory of Aging. Redox Biology, 11, 365-374. https://doi.org/10.1016/j.redox.2016.12.026 |
| [35] | Campisi, J. (2005) Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors. Cell, 120, 513-522. https://doi.org/10.1016/j.cell.2005.02.003 |
| [36] | Shelton, D.N., Chang, E., Whittier, P.S., Choi, D. and Funk, W.D. (1999) Microarray Analysis of Replicative Senescence. Current Biology, 9, 939-945. https://doi.org/10.1016/s0960-9822(99)80420-5 |
| [37] | Aggarwal, B.B. (2003) Signalling Pathways of the TNF Superfamily: A Double-Edged Sword. Nature Reviews Immunology, 3, 745-756. https://doi.org/10.1038/nri1184 |
| [38] | Micheau, O. and Tschopp, J. (2003) Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes. Cell, 114, 181-190. https://doi.org/10.1016/s0092-8674(03)00521-x |
| [39] | Hayden, M.S. and Ghosh, S. (2012) NF-κB, the First Quarter-Century: Remarkable Progress and Outstanding Questions. Genes & Development, 26, 203-234. https://doi.org/10.1101/gad.183434.111 |
| [40] | Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J.E., et al. (2011) Control of the Senescence-Associated Secretory Phenotype by NF-κB Promotes Senescence and Enhances Chemosensitivity. Genes & Development, 25, 2125-2136. https://doi.org/10.1101/gad.17276711 |
| [41] | Wertz, I.E., O’Rourke, K.M., Zhou, H., Eby, M., Aravind, L., Seshagiri, S., et al. (2004) De-Ubiquitination and Ubiquitin Ligase Domains of A20 Downregulate NF-κB Signalling. Nature, 430, 694-699. https://doi.org/10.1038/nature02794 |
| [42] | Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C.J., et al. (2015) mTOR Regulates MAPKAPK2 Translation to Control the Senescence-Associated Secretory Phenotype. Nature Cell Biology, 17, 1205-1217. https://doi.org/10.1038/ncb3225 |
| [43] | Bi, S., Liu, Z., Wu, Z., Wang, Z., Liu, X., Wang, S., et al. (2020) SIRT7 Antagonizes Human Stem Cell Aging as a Heterochromatin Stabilizer. Protein & Cell, 11, 483-504. https://doi.org/10.1007/s13238-020-00728-4 |
| [44] | Liu, X., Liu, Z., Wu, Z., Ren, J., Fan, Y., Sun, L., et al. (2023) Resurrection of Endogenous Retroviruses during Aging Reinforces Senescence. Cell, 186, 287-304.e26. https://doi.org/10.1016/j.cell.2022.12.017 |
| [45] | Glück, S., Guey, B., Gulen, M.F., Wolter, K., Kang, T., Schmacke, N.A., et al. (2017) Innate Immune Sensing of Cytosolic Chromatin Fragments through CGAS Promotes Senescence. Nature Cell Biology, 19, 1061-1070. https://doi.org/10.1038/ncb3586 |
| [46] | Lyon, A.S., Peeples, W.B. and Rosen, M.K. (2020) A Framework for Understanding the Functions of Biomolecular Condensates across Scales. Nature Reviews Molecular Cell Biology, 22, 215-235. https://doi.org/10.1038/s41580-020-00303-z |
| [47] | Sabari, B.R., Dall’Agnese, A. and Young, R.A. (2020) Biomolecular Condensates in the Nucleus. Trends in Biochemical Sciences, 45, 961-977. https://doi.org/10.1016/j.tibs.2020.06.007 |
| [48] | Brangwynne, C.P., Eckmann, C.R., Courson, D.S., Rybarska, A., Hoege, C., Gharakhani, J., et al. (2009) Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/condensation. Science, 324, 1729-1732. https://doi.org/10.1126/science.1172046 |
| [49] | Galganski, L., Urbanek, M.O. and Krzyzosiak, W.J. (2017) Nuclear Speckles: Molecular Organization, Biological Function and Role in Disease. Nucleic Acids Research, 45, 10350-10368. https://doi.org/10.1093/nar/gkx759 |
| [50] | Buchwalter, A. and Hetzer, M.W. (2017) Nucleolar Expansion and Elevated Protein Translation in Premature Aging. Nature Communications, 8, Article No. 328. https://doi.org/10.1038/s41467-017-00322-z |
| [51] | Fox, A.H. and Lamond, A.I. (2010) Paraspeckles. Cold Spring Harbor Perspectives in Biology, 2, a000687. https://doi.org/10.1101/cshperspect.a000687 |
| [52] | Lallemand-Breitenbach, V. and de Thé, H. (2018) PML Nuclear Bodies: From Architecture to Function. Current Opinion in Cell Biology, 52, 154-161. https://doi.org/10.1016/j.ceb.2018.03.011 |
| [53] | Hall, B.M., Balan, V., Gleiberman, A.S., Strom, E., Krasnov, P., Virtuoso, L.P., et al. (2017) p16(Ink4a) and Senescence-Associated β-Galactosidase Can Be Induced in Macrophages as Part of a Reversible Response to Physiological Stimuli. Aging, 9, 1867-1884. https://doi.org/10.18632/aging.101268 |
| [54] | Akbarian, S., Beeri, M.S. and Haroutunian, V. (2013) Epigenetic Determinants of Healthy and Diseased Brain Aging and Cognition. JAMA Neurology, 70, 711-718. https://doi.org/10.1001/jamaneurol.2013.1459 |
| [55] | Li, Y., Yu, H., Chen, C., Li, S., Zhang, Z., Xu, H., et al. (2020) Proteomic Profile of Mouse Brain Aging Contributions to Mitochondrial Dysfunction, DNA Oxidative Damage, Loss of Neurotrophic Factor, and Synaptic and Ribosomal Proteins. Oxidative Medicine and Cellular Longevity, 2020, Article ID: 5408452. https://doi.org/10.1155/2020/5408452 |
| [56] | Duran‐Ortiz, S., List, E.O., Ikeno, Y., Young, J., Basu, R., Bell, S., et al. (2021) Growth Hormone Receptor Gene Disruption in Mature‐Adult Mice Improves Male Insulin Sensitivity and Extends Female Lifespan. Aging Cell, 20, e13506. https://doi.org/10.1111/acel.13506 |
| [57] | Covarrubias, A.J., Perrone, R., Grozio, A. and Verdin, E. (2020) NAD+ Metabolism and Its Roles in Cellular Processes during Ageing. Nature Reviews Molecular Cell Biology, 22, 119-141. https://doi.org/10.1038/s41580-020-00313-x |
| [58] | Chiu, M., Fan, L., Chen, T., Chen, Y., Chieh, J. and Horng, H. (2017) Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults. Frontiers in Aging Neuroscience, 9, Article No. 51. https://doi.org/10.3389/fnagi.2017.00051 |
| [59] | Cavedo, E., Lista, S., Houot, M., Vergallo, A., Grothe, M.J., Teipel, S., et al. (2020) Plasma Tau Correlates with Basal Forebrain Atrophy Rates in People at Risk for Alzheimer Disease. Neurology, 94, e30-e41. https://doi.org/10.1212/wnl.0000000000008696 |
| [60] | Kaeser, S.A., Lehallier, B., Thinggaard, M., Häsler, L.M., Apel, A., Bergmann, C., et al. (2021) A Neuronal Blood Marker Is Associated with Mortality in Old Age. Nature Aging, 1, 218-225. https://doi.org/10.1038/s43587-021-00028-4 |
| [61] | Henjum, K., Almdahl, I.S., Årskog, V., Minthon, L., Hansson, O., Fladby, T., et al. (2016) Cerebrospinal Fluid Soluble TREM2 in Aging and Alzheimer’s Disease. Alzheimer’s Research & Therapy, 8, Article No. 17. https://doi.org/10.1186/s13195-016-0182-1 |
| [62] | Zhao, A., Jiao, Y., Ye, G., Kang, W., Tan, L., Li, Y., et al. (2022) Soluble TREM2 Levels Associate with Conversion from Mild Cognitive Impairment to Alzheimer’s Disease. Journal of Clinical Investigation, 132, e158708. https://doi.org/10.1172/jci158708 |
| [63] | Abdelhak, A., Hottenrott, T., Morenas-Rodríguez, E., Suárez-Calvet, M., Zettl, U.K., Haass, C., et al. (2019) Glial Activation Markers in CSF and Serum from Patients with Primary Progressive Multiple Sclerosis: Potential of Serum GFAP as Disease Severity Marker? Frontiers in Neurology, 10, Article No. 280. https://doi.org/10.3389/fneur.2019.00280 |
| [64] | Wruck, W. and Adjaye, J. (2020) Meta-Analysis of Human Prefrontal Cortex Reveals Activation of GFAP and Decline of Synaptic Transmission in the Aging Brain. Acta Neuropathologica Communications, 8, Article No. 26. https://doi.org/10.1186/s40478-020-00907-8 |
| [65] | Pelletier, A., Bernard, C., Dilharreguy, B., Helmer, C., Le Goff, M., Chanraud, S., et al. (2017) Patterns of Brain Atrophy Associated with Episodic Memory and Semantic Fluency Decline in Aging. Aging, 9, 741-752. https://doi.org/10.18632/aging.101186 |
| [66] | Hoogendam, Y.Y., van der Lijn, F., Vernooij, M.W., Hofman, A., Niessen, W.J., van der Lugt, A., et al. (2014) Older Age Relates to Worsening of Fine Motor Skills: A Population-Based Study of Middle-Aged and Elderly Persons. Frontiers in Aging Neuroscience, 6, Article No. 259. https://doi.org/10.3389/fnagi.2014.00259 |
| [67] | Zhang, L., Guo, J., Liu, Y., Sun, S., Liu, B., Yang, Q., et al. (2023) A Framework of Biomarkers for Vascular Aging: A Consensus Statement by the Aging Biomarker Consortium. Life Medicine, 2, lnad033. https://doi.org/10.1093/lifemedi/lnad033 |
| [68] | Loessner, A., Alavi, A., Lewandrowski, K.U., et al. (1995) Regional Cerebral Function Determined by FDG-PET in Healthy Volunteers: Normal Patterns and Changes with Age. The Journal of Nuclear Medicine, 36, 1141-1149. |
| [69] | Pagani, M., Giuliani, A., Öberg, J., De Carli, F., Morbelli, S., Girtler, N., et al. (2017) Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of 18F-Fdg PET Data. Journal of Nuclear Medicine, 58, 1132-1139. https://doi.org/10.2967/jnumed.116.184309 |
| [70] | Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., et al. (2019) Length‐Independent Telomere Damage Drives Post‐Mitotic Cardiomyocyte Senescence. The EMBO Journal, 38, e100492. https://doi.org/10.15252/embj.2018100492 |
| [71] | Piera-Velazquez, S. and Jimenez, S.A. (2019) Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases. Physiological Reviews, 99, 1281-1324. https://doi.org/10.1152/physrev.00021.2018 |
| [72] | Dai, D., Chen, T., Johnson, S.C., Szeto, H. and Rabinovitch, P.S. (2012) Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease. Antioxidants & Redox Signaling, 16, 1492-1526. https://doi.org/10.1089/ars.2011.4179 |
| [73] | Ma, S., Sun, S., Li, J., Fan, Y., Qu, J., Sun, L., et al. (2020) Single-Cell Transcriptomic Atlas of Primate Cardiopulmonary Aging. Cell Research, 31, 415-432. https://doi.org/10.1038/s41422-020-00412-6 |
| [74] | Zhang, Y., Zheng, Y., Wang, S., Fan, Y., Ye, Y., Jing, Y., et al. (2022) Single-Nucleus Transcriptomics Reveals a Gatekeeper Role for FOXP1 in Primate Cardiac Aging. Protein & Cell, 14, 279-293. https://doi.org/10.1093/procel/pwac038 |
| [75] | Yoshida, Y., Nakanishi, K., Daimon, M., Ishiwata, J., Sawada, N., Hirokawa, M., et al. (2019) Alteration of Cardiac Performance and Serum B-Type Natriuretic Peptide Level in Healthy Aging. Journal of the American College of Cardiology, 74, 1789-1800. https://doi.org/10.1016/j.jacc.2019.07.080 |
| [76] | de Lemos, J.A., Drazner, M.H., Omland, T., Ayers, C.R., Khera, A., Rohatgi, A., et al. (2010) Association of Troponin T Detected with a Highly Sensitive Assay and Cardiac Structure and Mortality Risk in the General Population. JAMA, 304, 2503-2512. https://doi.org/10.1001/jama.2010.1768 |
| [77] | Zhang, W., Che, Y., Tang, X., Chen, S., Song, M., Wang, L., et al. (2023) A Biomarker Framework for Cardiac Aging: The Aging Biomarker Consortium Consensus Statement. Life Medicine, 2, lnad035. https://doi.org/10.1093/lifemedi/lnad035 |
| [78] | Zhang, L., Guo, J., Liu, Y., Sun, S., Liu, B., Yang, Q., et al. (2023) A Framework of Biomarkers for Vascular Aging: A Consensus Statement by the Aging Biomarker Consortium. Life Medicine, 2, lnad033. https://doi.org/10.1093/lifemedi/lnad033 |
| [79] | Tian, X. and Li, Y. (2014) Endothelial Cell Senescence and Age-Related Vascular Diseases. Journal of Genetics and Genomics, 41, 485-495. https://doi.org/10.1016/j.jgg.2014.08.001 |
| [80] | Yang, D., McCrann, D.J., Nguyen, H., Hilaire, C.S., DePinho, R.A., Jones, M.R., et al. (2007) Increased Polyploidy in Aortic Vascular Smooth Muscle Cells during Aging Is Marked by Cellular Senescence. Aging Cell, 6, 257-260. https://doi.org/10.1111/j.1474-9726.2007.00274.x |
| [81] | Bhayadia, R., Schmidt, B.M.W., Melk, A. and Hömme, M. (2015) Senescence-Induced Oxidative Stress Causes Endothelial Dysfunction. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 71, 161-169. https://doi.org/10.1093/gerona/glv008 |
| [82] | Gao, P., Gao, P., Choi, M., Chegireddy, K., Slivano, O.J., Zhao, J., et al. (2020) Transcriptome Analysis of Mouse Aortae Reveals Multiple Novel Pathways Regulated by Aging. Aging, 12, 15603-15623. https://doi.org/10.18632/aging.103652 |
| [83] | Yu, H., Liao, K., Hu, Y., Lv, D., Luo, M., Liu, Q., et al. (2022) Role of the CGAS-Sting Pathway in Aging-Related Endothelial Dysfunction. Aging and disease, 13, 1901-1918. https://doi.org/10.14336/ad.2022.0316 |
| [84] | Minamino, T. and Komuro, I. (2007) Vascular Cell Senescence: Contribution to Atherosclerosis. Circulation Research, 100, 15-26. https://doi.org/10.1161/01.res.0000256837.40544.4a |
| [85] | Wang, S., Hu, S. and Mao, Y. (2021) The Mechanisms of Vascular Aging. Aging Medicine, 4, 153-158. https://doi.org/10.1002/agm2.12151 |
| [86] | Aschacher, T., Geisler, D., Lenz, V., Aschacher, O., Winkler, B., Schaefer, A., et al. (2022) Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm. International Journal of Molecular Sciences, 23, Article No. 15498. https://doi.org/10.3390/ijms232415498 |
| [87] | Chen, H., Wang, F., Gao, P., Pei, J., Liu, Y., Xu, T., et al. (2016) Age-Associated Sirtuin 1 Reduction in Vascular Smooth Muscle Links Vascular Senescence and Inflammation to Abdominal Aortic Aneurysm. Circulation Research, 119, 1076-1088. https://doi.org/10.1161/circresaha.116.308895 |
| [88] | Horvath, S. (2013) DNA Methylation Age of Human Tissues and Cell Types. Genome Biology, 14, R115. https://doi.org/10.1186/gb-2013-14-10-r115 |
| [89] | Levine, M.E., Lu, A.T., Quach, A., Chen, B.H., Assimes, T.L., Bandinelli, S., et al. (2018) An Epigenetic Biomarker of Aging for Lifespan and Healthspan. Aging, 10, 573-591. https://doi.org/10.18632/aging.101414 |
| [90] | Lu, A.T., Quach, A., Wilson, J.G., Reiner, A.P., Aviv, A., Raj, K., et al. (2019) DNA Methylation Grimage Strongly Predicts Lifespan and Healthspan. Aging, 11, 303-327. https://doi.org/10.18632/aging.101684 |
| [91] | Zbieć-Piekarska, R., Spólnicka, M., Kupiec, T., Parys-Proszek, A., Makowska, Ż., Pałeczka, A., et al. (2015) Development of a Forensically Useful Age Prediction Method Based on DNA Methylation Analysis. Forensic Science International: Genetics, 17, 173-179. https://doi.org/10.1016/j.fsigen.2015.05.001 |
| [92] | Peters, M.J., Joehanes, R., Pilling, L.C., et al. (2015) The Transcriptional Landscape of Age in Human Peripheral Blood. Nature Communications, 6, Article No. 8570. |
| [93] | Fleischer, J.G., Schulte, R., Tsai, H.H., Tyagi, S., Ibarra, A., Shokhirev, M.N., et al. (2018) Predicting Age from the Transcriptome of Human Dermal Fibroblasts. Genome Biology, 19, Article No. 221. https://doi.org/10.1186/s13059-018-1599-6 |
| [94] | Tanaka, T., Biancotto, A., Moaddel, R., Moore, A.Z., Gonzalez‐Freire, M., Aon, M.A., et al. (2018) Plasma Proteomic Signature of Age in Healthy Humans. Aging Cell, 17, e12799. https://doi.org/10.1111/acel.12799 |
| [95] | Herzog, C.M.S., Goeminne, L.J.E., Poganik, J.R., Barzilai, N., Belsky, D.W., Betts-LaCroix, J., et al. (2024) Challenges and Recommendations for the Translation of Biomarkers of Aging. Nature Aging, 4, 1372-1383. https://doi.org/10.1038/s43587-024-00683-3 |
