CoChat
Sign Up
Cited by 88

The DOI matches its Crossref record; 117 of the 117 references it cites were found in a registry or an index.

Emerging insights in senescence: pathways from preclinical models to therapeutic innovations

Mansfield, Luke, Ramponi, Valentina, Gupta, Kavya, Stevenson, Thomas, Mathew, Abraham Binoy, Barinda, Agian Jeffilano, Herbstein, Florencia, Morsli, Samir·2024·npj Aging
DOI 10.1038/s41514-024-00181-1PMC PMC11584693
Open this paper in CoChat — free account

Abstract

Senescence is a crucial hallmark of ageing and a significant contributor to the pathology of age-related disorders. As committee members of the young International Cell Senescence Association (yICSA), we aim to synthesise recent advancements in the identification, characterisation, and therapeutic targeting of senescence for clinical translation. We explore novel molecular techniques that have enhanced our understanding of senescent cell heterogeneity and their roles in tissue regeneration and pathology. Additionally, we delve into in vivo models of senescence, both non-mammalian and mammalian, to highlight tools available for advancing the contextual understanding of in vivo senescence. Furthermore, we discuss innovative diagnostic tools and senotherapeutic approaches, emphasising their potential for clinical application. Future directions of senescence research are explored, underscoring the need for precise, context-specific senescence classification and the integration of advanced technologies such as machine learning, long-read sequencing, and multifunctional senoprobes and senolytics. The dual role of senescence in promoting tissue homoeostasis and contributing to chronic diseases highlights the complexity of targeting these cells for improved clinical outcomes.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41514-024-00181-1

Cites

117 of 117 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 345

  1. Hayflick, L. & Moorhead, P. S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621 (1961). · DOI · Paper page
  2. Georgakopoulou, E., Evangelou, K. & Gorgoulis, V. G. Premalignant lesions and cellular senescence. In Cellular Senescence in Disease 29–60 (Elsevier, 2022). · DOI
  3. He, S. & Sharpless, N. E. Senescence in health and disease. Cell 169, 1000–1011 (2017). · DOI · Paper page
  4. Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018). · DOI · Paper page
  5. Coppé, J.-P., Desprez, P.-Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010). · DOI · Paper page
  6. Lopes-Paciencia, S. et al. The senescence-associated secretory phenotype and its regulation. Cytokine 117, 15–22 (2019). · DOI · Paper page
  7. Herbstein, F., et al. The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway. Aging Cell https://doi.org/10.1111/acel.14258 (2024). · DOI
  8. Wiley, C. D. et al. Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis. Cell Metab. 33, 1124–1136.e5 (2021). · DOI · Paper page
  9. Khosla, S. A pipeline for senolytics. J. Clin. Invest. https://doi.org/10.1172/JCI180558 (2024). · DOI
  10. Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017). · DOI · Paper page
  11. Austad, S. N. & Bartke, A. Sex differences in longevity and in responses to anti-aging interventions: a mini-review. Gerontology 62, 40–46 (2015). · DOI
  12. Kohli, J. et al. Algorithmic assessment of cellular senescence in experimental and clinical specimens. Nat. Protoc. 16, 2471–2498 (2021). · DOI · Paper page
  13. Engeland, K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ. 29, 946–960 (2022). · DOI
  14. El-Deiry, W. S. et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 54, 1169–1174 (1994).
  15. Rayess, H., Wang, M. B. & Srivatsan, E. S. Cellular senescence and tumor suppressor gene p16. Int. J. Cancer 130, 1715–1725 (2012). · DOI · Paper page
  16. Martínez-Zamudio, R. I. et al. Senescence-associated β-galactosidase reveals the abundance of senescent CD8 + T cells in aging humans. Aging Cell 20, e13344 (2021). · DOI · Paper page
  17. Piechota, M. et al. Is senescence-associated β-galactosidase a marker of neuronal senescence? Oncotarget 7, 81099–81109 (2016). · DOI
  18. Gréchez-Cassiau, A., Rayet, B., Guillaumond, F., Teboul, M. & Delaunay, F. The circadian clock component BMAL1 is a critical regulator of p21WAF1/CIP1 expression and hepatocyte proliferation. J. Biol. Chem. 283, 4535–4542 (2008). · DOI
  19. Avelar, R. A. et al. A multidimensional systems biology analysis of cellular senescence in aging and disease. Genome Biol. 21, 91 (2020). · DOI · Paper page
  20. Scanlan, R. L. et al. Systematic transcriptomic analysis and temporal modelling of human fibroblast senescence. Front. Aging 5, 1448543 (2024). · DOI
  21. Guduric‐Fuchs, J. et al. A new gene signature for endothelial senescence identifies self‐RNA sensing by retinoic acid‐inducible gene I as a molecular facilitator of vascular aging. Aging Cell https://doi.org/10.1111/acel.14240 (2024). · DOI
  22. Hughes, B. et al. SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify senescent cells for the detection of an in vivo senescent cell burden. Preprint at bioRxiv https://doi.org/10.1101/2023.10.23.563515 (2023). · DOI
  23. Berardi, D. et al. Integration of mass-spectrometry-based global metabolomics and proteomics analysis to characterise different senescence induced molecular sub-phenotypes. Preprint at bioRxiv https://doi.org/10.1101/2022.11.30.518588 (2022). · DOI
  24. Kim, J. Y., Atanassov, I., Dethloff, F., Kroczek, L. & Langer, T. Time-resolved proteomic analyses of senescence highlight metabolic rewiring of mitochondria. Life Sci. Alliance https://doi.org/10.26508/lsa.202302127 (2023). · DOI
  25. Zhang, L. et al. Analysis of somatic mutations in senescent cells using single-cell whole-genome sequencing. Aging Biol. 1, 20230005 (2023). · DOI
  26. Nelson, D. M. et al. Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability. Genome Biol. 17, 158 (2016). · DOI
  27. Chandra, T. et al. Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Mol. Cell 47, 203–214 (2012). · DOI · Paper page
  28. Zhang, B. et al. KDM4 orchestrates epigenomic remodeling of senescent cells and potentiates the senescence-associated secretory phenotype. Nat. Aging 1, 454–472 (2021). · DOI
  29. Xie, W. et al. DNA methylation patterns separate senescence from transformation potential and indicate cancer risk. Cancer Cell 33, 309–321.e5 (2018). · DOI · Paper page
  30. Matsudaira, T. et al. Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype. Commun. Biol. 6, 665 (2023). · DOI · Paper page
  31. Bigagli, E. et al. Long-term neuroglial cocultures as a brain aging model: hallmarks of senescence, MicroRNA expression profiles, and comparison with in vivo models. J. Gerontol. A Biol. Sci. Med. Sci. 71, 50–60 (2016). · DOI
  32. Chou, S.-M., Yen, Y.-H., Yuan, F., Zhang, S.-C. & Chong, C.-M. Neuronal senescence in the aged brain. Aging Dis. 14, 1618–1632 (2023). · DOI
  33. Palmer, A. et al. Expression of p16 within myenteric neurons of the aged colon: a potential marker of declining function. Front. Neurosci. 15, 747067 (2021). · DOI
  34. Grosse, L. et al. Defined p16High senescent cell types are indispensable for mouse healthspan. Cell Metab. 32, 87–99.e6 (2020). · DOI · Paper page
  35. Poisson, J. et al. Liver sinusoidal endothelial cells: physiology and role in liver diseases. J. Hepatol. 66, 212–227 (2017). · DOI · Paper page
  36. Wang, B. et al. An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo. Nat. Aging 1, 962–973 (2021). · DOI · Paper page
  37. Saul, D. et al. Distinct secretomes in p16- and p21- positive senescent cells across tissues. Preprint at bioRxiv https://doi.org/10.1101/2023.12.05.569858 (2023). · DOI · Paper page
  38. Evans, S. A. et al. Single-Cell Transcriptomics Reveals Global Markers of Transcriptional Diversity across Different Forms of Cellular Senescence. Aging Biol. 1, 20230008 (2023). · DOI
  39. Yousefzadeh, M. J. et al. Mouse models of accelerated cellular senescence. Methods Mol. Biol. 1896, 203–230 (2019). · DOI
  40. Koon, A. C. & Chan, H. Y. E. Drosophila melanogaster as a model organism to study RNA toxicity of repeat expansion-associated neurodegenerative and neuromuscular diseases. Front. Cell. Neurosci. 11, 70 (2017). · DOI
  41. Lohr, J. N., Galimov, E. R. & Gems, D. Does senescence promote fitness in Caenorhabditis elegans by causing death? Ageing Res. Rev. 50, 58–71 (2019). · DOI
  42. Ezcurra, M. et al. C. elegans eats its own intestine to make yolk leading to multiple senescent pathologies. Curr. Biol. 28, 2544–2556.e5 (2018). · DOI
  43. Wang, J. et al. A senomorphlytic three-drug combination discovered in Salsola collina for delaying aging phenotypes and extending healthspan. Adv. Sci. https://doi.org/10.1002/advs.202401862 (2024). · DOI
  44. Zhang, S., Li, F., Zhou, T., Wang, G. & Li, Z. Caenorhabditis elegans as a useful model for studying aging mutations. Front. Endocrinol. 11, 554994 (2020). · DOI
  45. Kim, Y., Park, Y., Hwang, J. & Kwack, K. Comparative genomic analysis of the human and nematode Caenorhabditis elegans uncovers potential reproductive genes and disease associations in humans. Physiol. Genom. 50, 1002–1014 (2018). · DOI
  46. Venz, R. et al. In-vivo screening implicates endoribonuclease Regnase-1 in modulating senescence-associated lysosomal changes. Geroscience 46, 1499–1514 (2024). · DOI
  47. Kern, C. C. et al. C. elegans ageing is accelerated by a self-destructive reproductive programme. Nat. Commun. 14, 4381 (2023). · DOI
  48. Jennings, B. H. Drosophila – a versatile model in biology & medicine. Mater. Today 14, 190–195 (2011). · DOI
  49. Ito, T. & Igaki, T. Dissecting cellular senescence and SASP in Drosophila. Inflamm. Regen. 36, 25 (2016). · DOI
  50. Garcia-Arias, J. M., Pinal, N., Cristobal-Vargas, S., Estella, C. & Morata, G. Lack of apoptosis leads to cellular senescence and tumorigenesis in Drosophila epithelial cells. Cell Death Discov. 9, 281 (2023). · DOI · Paper page
  51. Lorjiim, W. M. et al. Senescence and oxidative stress toxicities induced by lamivudine and tenofovir in Drosophila melanogaster. Ann. Pharm. Fr. 80, 864–875 (2022). · DOI
  52. Byrns, C. N. et al. Senescent glia link mitochondrial dysfunction and lipid accumulation. Nature 630, 475–483 (2024). · DOI
  53. Poeschla, M. & Valenzano, D. R. The turquoise killifish: a genetically tractable model for the study of aging. J. Exp. Biol. https://doi.org/10.1242/jeb.209296 (2020). · DOI
  54. Krug, J. et al. Generation of a transparent killifish line through multiplex CRISPR/Cas9mediated gene inactivation. eLife https://doi.org/10.7554/eLife.81549 (2023). · DOI
  55. Ruparelia, A. A. et al. The African killifish: a short-lived vertebrate model to study the biology of sarcopenia and longevity. Aging Cell 23, e13862 (2024). · DOI
  56. Harel, I. The turquoise killifish. Nat. Methods 19, 1150–1151 (2022). · DOI
  57. Van Houcke, J. et al. A short dasatinib and quercetin treatment is sufficient to reinstate potent adult neuroregenesis in the aged killifish. npj Regen. Med. 8, 31 (2023). · DOI · Paper page
  58. Moses, E. et al. The killifish germline regulates longevity and somatic repair in a sex-specific manner. Nat. Aging 4, 791–813 (2024). · DOI
  59. Lieschke, G. J. & Currie, P. D. Animal models of human disease: zebrafish swim into view. Nat. Rev. Genet. 8, 353–367 (2007). · DOI
  60. Choi, T.-Y., Choi, T.-I., Lee, Y.-R., Choe, S.-K. & Kim, C.-H. Zebrafish as an animal model for biomedical research. Exp. Mol. Med. 53, 310–317 (2021). · DOI
  61. Gilbert, M. J. H., Zerulla, T. C. & Tierney, K. B. Zebrafish (Danio rerio) as a model for the study of aging and exercise: physical ability and trainability decrease with age. Exp. Gerontol. 50, 106–113 (2014). · DOI
  62. Van Houcke, J., De Groef, L., Dekeyster, E. & Moons, L. The zebrafish as a gerontology model in nervous system aging, disease, and repair. Ageing Res. Rev. 24, 358–368 (2015). · DOI
  63. Wang, G. et al. First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass. eLife https://doi.org/10.7554/eLife.08261 (2015). · DOI
  64. Patton, E. E., Zon, L. I. & Langenau, D. M. Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials. Nat. Rev. Drug Discov. 20, 611–628 (2021). · DOI
  65. Carneiro, M. C. et al. Short telomeres in key tissues initiate local and systemic aging in zebrafish. PLoS Genet. 12, e1005798 (2016). · DOI
  66. Biessmann, H. & Mason, J. M. Telomere maintenance without telomerase. Chromosoma 106, 63–69 (1997). · DOI
  67. Wienholds, E. et al. Efficient target-selected mutagenesis in zebrafish. Genome Res. 13, 2700–2707 (2003). · DOI
  68. El Maï, M. et al. Gut-specific telomerase expression counteracts systemic aging in telomerase-deficient zebrafish. Nat. Aging 3, 567–584 (2023). · DOI
  69. Gerhard, G. S. et al. Life spans and senescent phenotypes in two strains of Zebrafish (Danio rerio). Exp. Gerontol. 37, 1055–1068 (2002). · DOI
  70. Kishi, S. et al. The identification of zebrafish mutants showing alterations in senescence-associated biomarkers. PLoS Genet. 4, e1000152 (2008). · DOI
  71. Kishi, S. et al. The zebrafish as a vertebrate model of functional aging and very gradual senescence. Exp. Gerontol. 38, 777–786 (2003). · DOI
  72. Koshimizu, E. et al. Embryonic senescence and laminopathies in a progeroid zebrafish model. PLoS ONE 6, e17688 (2011). · DOI
  73. Almaida-Pagán, P. F., Lucas-Sánchez, A. & Tocher, D. R. Changes in mitochondrial membrane composition and oxidative status during rapid growth, maturation and aging in zebrafish, Danio rerio. Biochim. Biophys. Acta 1841, 1003–1011 (2014). · DOI
  74. Ruhl, T. et al. Oxidation and cognitive impairment in the aging zebrafish. Gerontology 62, 47–57 (2015). · DOI
  75. Da Silva-Álvarez, S. et al. Developmentally-programmed cellular senescence is conserved and widespread in zebrafish. Aging 12, 17895–17901 (2020). · DOI
  76. Rosa, J. G. S., Lima, C. & Lopes-Ferreira, M. Zebrafish larvae behavior models as a tool for drug screenings and pre-clinical trials: a review. Int. J. Mol. Sci. https://doi.org/10.3390/ijms23126647 (2022). · DOI
  77. Min, S. & Whited, J. L. Limb blastema formation: how much do we know at a genetic and epigenetic level? J. Biol. Chem. 299, 102858 (2023). · DOI
  78. Yun, M. H., Davaapil, H. & Brockes, J. P. Recurrent turnover of senescent cells during regeneration of a complex structure. eLife https://doi.org/10.7554/eLife.05505 (2015). · DOI · Paper page
  79. Davaapil, H., Brockes, J. P. & Yun, M. H. Conserved and novel functions of programmed cellular senescence during vertebrate development. Development 144, 106–114 (2017).
  80. Villiard, É. et al. Senescence gives insights into the morphogenetic evolution of anamniotes. Biol. Open 6, 891–896 (2017).
  81. Yun, M. H. Salamander insights into ageing and rejuvenation. Front. Cell Dev. Biol. 9, 689062 (2021). · DOI
  82. Mounkes, L. C., Kozlov, S., Hernandez, L., Sullivan, T. & Stewart, C. L. A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 423, 298–301 (2003). · DOI
  83. Ramírez, C. L., Cadiñanos, J., Varela, I., Freije, J. M. P. & López-Otín, C. Human progeroid syndromes, aging and cancer: new genetic and epigenetic insights into old questions. Cell. Mol. Life Sci. 64, 155–170 (2007). · DOI
  84. Gurkar, A. U. & Niedernhofer, L. J. Comparison of mice with accelerated aging caused by distinct mechanisms. Exp. Gerontol. 68, 43–50 (2015). · DOI
  85. Bramwell, L. R. & Harries, L. W. Senescence, regulators of alternative splicing and effects of trametinib treatment in progeroid syndromes. Geroscience 46, 1861–1879 (2024). · DOI
  86. Zhang, N. et al. Unique progerin C-terminal peptide ameliorates Hutchinson-Gilford progeria syndrome phenotype by rescuing BUBR1. Nat. Aging 3, 185–201 (2023). · DOI
  87. Park, S.-H., Xie, S., Rao, C. V. & Dai, W. Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence. J. Hematol. Oncol. 9, 7 (2016). · DOI
  88. Kim, D. E. et al. Deficiency in the DNA repair protein ERCC1 triggers a link between senescence and apoptosis in human fibroblasts and mouse skin. Aging Cell 19, e13072 (2020). · DOI
  89. Yousefzadeh, M. J. et al. Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging Cell 19, e13094 (2020). · DOI · Paper page
  90. Zhang, J. et al. Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice. Cell Death Dis. 15, 380 (2024). · DOI
  91. Han, Z. Z., Fleet, A. & Larrieu, D. Can accelerated ageing models inform us on age-related tauopathies? Aging Cell 22, e13830 (2023). · DOI
  92. Rall-Scharpf, M. et al. Sex-specific differences in DNA double-strand break repair of cycling human lymphocytes during aging. Aging 13, 21066–21089 (2021). · DOI
  93. Fischer, K. E. & Riddle, N. C. Sex differences in aging: genomic instability. J. Gerontol. A Biol. Sci. Med. Sci. 73, 166–174 (2018). · DOI
  94. de Boer, J. et al. Premature aging in mice deficient in DNA repair and transcription. Science 296, 1276–1279 (2002). · DOI · Paper page
  95. Stewart, C. L., Kozlov, S., Fong, L. G. & Young, S. G. Mouse models of the laminopathies. Exp. Cell Res. 313, 2144–2156 (2007). · DOI
  96. Gonzalo, S. & Coll-Bonfill, N. Genomic instability and innate immune responses to self-DNA in progeria. Geroscience 41, 255–266 (2019). · DOI
  97. Wang, Y. et al. Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2118695119 (2022). · DOI
  98. Leung, G. K. et al. Biochemical studies of Zmpste24-deficient mice. J. Biol. Chem. 276, 29051–29058 (2001). · DOI
  99. Bergo, M. O. et al. Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc. Natl Acad. Sci. USA 99, 13049–13054 (2002). · DOI
  100. Lanske, B. & Razzaque, M. S. Premature aging in klotho mutant mice: cause or consequence? Ageing Res. Rev. 6, 73–79 (2007). · DOI
  101. Akiguchi, I. et al. SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda’s legacy and future directions. Neuropathology 37, 293–305 (2017). · DOI
  102. Austad, S. N. Methusaleh’s Zoo: how nature provides us with clues for extending human health span. J. Comp. Pathol. 142, S10–S21 (2010). · DOI
  103. Brunet-Rossinni, A. K. & Austad, S. N. Ageing studies on bats: a review. Biogerontology 5, 211–222 (2004). · DOI
  104. Fleischer, T., Gampe, J., Scheuerlein, A. & Kerth, G. Rare catastrophic events drive population dynamics in a bat species with negligible senescence. Sci. Rep. 7, 7370 (2017). · DOI
  105. Brunet Rossinni, A. K. Testing the free radical theory of aging in bats. Ann. N. Y. Acad. Sci. 1019, 506–508 (2004). · DOI
  106. Foley, N. M. et al. Growing old, yet staying young: the role of telomeres in bats’ exceptional longevity. Sci. Adv. 4, eaao0926 (2018). · DOI
  107. Oka, K., Yamakawa, M., Kawamura, Y., Kutsukake, N. & Miura, K. The naked mole-rat as a model for healthy aging. Annu. Rev. Anim. Biosci. 11, 207–226 (2023). · DOI
  108. Evdokimov, A. et al. Naked mole rat cells display more efficient excision repair than mouse cells. Aging 10, 1454–1473 (2018). · DOI
  109. MacRae, S. L. et al. DNA repair in species with extreme lifespan differences. Aging 7, 1171–1184 (2015). · DOI
  110. Buffenstein, R. Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species. J. Comp. Physiol. B 178, 439–445 (2008). · DOI · Paper page
  111. Zhao, Y. et al. Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence. Proc. Natl Acad. Sci. USA 115, 1801–1806 (2018). · DOI
  112. Kawamura, Y. et al. Cellular senescence induction leads to progressive cell death via the INK4a-RB pathway in naked mole-rats. EMBO J. 42, e111133 (2023). · DOI
  113. Burd, C. E. et al. Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model. Cell 152, 340–351 (2013). · DOI · Paper page
  114. Hori, N. et al. Shaving black fur uncovers hidden issues in p16-3MR mice. Preprint at bioRxiv https://doi.org/10.1101/2024.06.24.600181 (2024). · DOI
  115. Liu, J.-Y. et al. Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence. Proc. Natl Acad. Sci. USA 116, 2603–2611 (2019). · DOI · Paper page
  116. Prieto, L. I. et al. Senescent alveolar macrophages promote early-stage lung tumorigenesis. Cancer Cell 41, 1261–1275.e6 (2023). · DOI · Paper page
  117. Yi, Z. et al. Generation of a p21 reporter mouse and its use to identify and eliminate p21high cells in vivo. Int. J. Mol. Sci. https://doi.org/10.3390/ijms24065565 (2023). · DOI
  118. Mikawa, R. et al. Elimination of p19ARF -expressing cells protects against pulmonary emphysema in mice. Aging Cell 17, e12827 (2018). · DOI
  119. Kawaguchi, K. et al. Protocol for assessing senescence-associated lung pathologies in mice. STAR Protoc. 2, 100993 (2021). · DOI
  120. Sun, J. et al. A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice. Nat. Commun. 13, 7028 (2022). · DOI · Paper page
  121. Lee, B. Y. et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 5, 187–195 (2006). · DOI · Paper page
  122. Minamino, T. et al. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation 105, 1541–1544 (2002). · DOI · Paper page
  123. Barinda, A. J. et al. Endothelial progeria induces adipose tissue senescence and impairs insulin sensitivity through senescence associated secretory phenotype. Nat. Commun. 11, 481 (2020). · DOI
  124. Stefanova, N. A. et al. Senescence-accelerated OXYS rats: a model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease. Cell Cycle 13, 898–909 (2014). · DOI
  125. Takahashi, K. et al. Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome. Nagoya J. Med. Sci. 76, 35–49 (2014).
  126. Krzystyniak, A. et al. Combination of dasatinib and quercetin improves cognitive abilities in aged male Wistar rats, alleviates inflammation and changes hippocampal synaptic plasticity and histone H3 methylation profile. Aging 14, 572–595 (2022). · DOI · Paper page
  127. Wanner, N., Barnhart, J., Apostolakis, N., Zlojutro, V. & Asosingh, K. Using the autofluorescence finder on the sony ID7000TM spectral cell analyzer to identify and unmix multiple highly autofluorescent murine lung populations. Front. Bioeng. Biotechnol. 10, 827987 (2022). · DOI
  128. Ansari, A. M. et al. Cellular GFP toxicity and immunogenicity: potential confounders in in vivo cell tracking experiments. Stem Cell Rev. 12, 553–559 (2016). · DOI
  129. Song, A. J. & Palmiter, R. D. Detecting and avoiding problems when using the Cre-lox system. Trends Genet. 34, 333–340 (2018). · DOI
  130. Hagemann-Jensen, M., Ziegenhain, C. & Sandberg, R. Scalable single-cell RNA sequencing from full transcripts with Smart-seq3xpress. Nat. Biotechnol. 40, 1452–1457 (2022). · DOI
  131. Clark, S. J. et al. scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells. Nat. Commun. 9, 781 (2018). · DOI · Paper page
  132. Gilson, P., Merlin, J.-L. & Harlé, A. Deciphering tumour heterogeneity: from tissue to liquid biopsy. Cancers https://doi.org/10.3390/cancers14061384 (2022). · DOI
  133. SenNet Consortium. NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health. Nat. Aging 2, 1090–1100 (2022). · DOI · Paper page
  134. Morsli, S., Doherty, G. J. & Muñoz-Espín, D. Activatable senoprobes and senolytics: Novel strategies to detect and target senescent cells. Mech. Ageing Dev. 202, 111618 (2022). · DOI
  135. He, Z. et al. Molecularly targeted fluorescent sensors for visualizing and tracking cellular senescence. Biosensors https://doi.org/10.3390/bios13090838 (2023). · DOI
  136. Li, J. et al. Recent advances in strategies for imaging detection and intervention of cellular senescence. Chembiochem 24, e202200364 (2023). · DOI
  137. Dimri, G. P. et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl Acad. Sci. USA 92, 9363–9367 (1995). · DOI · Paper page
  138. Dedic, B. et al. Senescence detection using reflected light. Aging Cell https://doi.org/10.1111/acel.14295 (2024). · DOI
  139. Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J. & Toussaint, O. Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat. Protoc. 4, 1798–1806 (2009). · DOI · Paper page
  140. Flor, A., Pagacz, J., Thompson, D. & Kron, S. Far-red fluorescent senescence-associated β-galactosidase probe for identification and enrichment of senescent tumor cells by flow cytometry. J. Vis. Exp. https://doi.org/10.3791/64176 (2022). · DOI
  141. Doura, T. et al. Detection of LacZ-positive cells in living tissue with single-cell resolution. Angew. Chem. Int. Ed. 55, 9620–9624 (2016). · DOI
  142. Lee, H. W. et al. Ratiometric two-photon fluorescent probe for quantitative detection of β-galactosidase activity in senescent cells. Anal. Chem. 86, 10001–10005 (2014). · DOI
  143. Zhang, J. et al. A novel near-infrared fluorescent probe for sensitive detection of β-galactosidase in living cells. Anal. Chim. Acta 968, 97–104 (2017). · DOI · Paper page
  144. Lozano-Torres, B. et al. An OFF-ON two-photon fluorescent probe for tracking cell senescence in vivo. J. Am. Chem. Soc. 139, 8808–8811 (2017). · DOI
  145. Lozano-Torres, B. et al. A two-photon probe based on naphthalimide-styrene fluorophore for the in vivo tracking of cellular senescence. Anal. Chem. 93, 3052–3060 (2021). · DOI
  146. Gu, K. et al. An enzyme-activatable probe liberating AIEgens: on-site sensing and long-term tracking of β-galactosidase in ovarian cancer cells. Chem. Sci. 10, 398–405 (2019). · DOI
  147. Cen, P. et al. Cellular senescence imaging and senolysis monitoring in cancer therapy based on a β-galactosidase-activated aggregation-induced emission luminogen. Acta Biomater. 179, 340–353 (2024). · DOI
  148. Rojas-Vázquez, S. et al. A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis. Nat. Commun. 15, 775 (2024). · DOI
  149. Agostini, A. et al. Targeted cargo delivery in senescent cells using capped mesoporous silica nanoparticles. Angew. Chem. Int. Ed. 51, 10556–10560 (2012). · DOI
  150. Lozano-Torres, B. et al. Real-time in vivo detection of cellular senescence through the controlled release of the NIR fluorescent dye nile blue. Angew. Chem. Int. Ed. 59, 15152–15156 (2020). · DOI
  151. Lozano-Torres, B. et al. β-galactosidase-activatable nile blue-based NIR senoprobe for the real-time detection of cellular senescence. Anal. Chem. 95, 1643–1651 (2023). · DOI
  152. Chu, J. C. H. et al. Detection and elimination of senescent cells with a self-assembled senescence-associated β-galactosidase-activatable nanophotosensitizer. J. Med. Chem. 67, 234–244 (2024). · DOI
  153. Yu, J. & Mason, R. P. Synthesis and characterization of novel lacZ gene reporter molecules: detection of beta-galactosidase activity by 19F nuclear magnetic resonance of polyglycosylated fluorinated vitamin B6. J. Med. Chem. 49, 1991–1999 (2006). · DOI
  154. Rabinowitz, Z. M. & Cui, L. Detecting cellular senescence in vivo: imagining imaging better. Aging Cancer 4, 97–1 (2023). · DOI
  155. Xiang, X. et al. Novel PET imaging probe for quantitative detection of senescence in vivo. J. Med. Chem. 67, 5924–5934 (2024). · DOI · Paper page
  156. Daldrup-Link, H. E. et al. Musculoskeletal imaging of senescence. Skeletal Radiol. https://doi.org/10.1007/s00256-024-04585-8 (2024). · DOI
  157. LaFougere, C. et al. Abstract CT095: update: a phase 1/2, open-label study to assess safety, tolerability, biodistribution, radiation dosimetry and PET imaging characteristics of [18F]FPyGal in comparison to in-vitro diagnostic for the assessment of senescence in oncological patients (NCT04536454). Cancer Res. 83, CT095–CT095 (2023). · DOI
  158. Krueger, M. A. et al. (2019). Abstract 1146: [18 F]FPyGal: a novel ß-galactosidase specific PET tracer for in vivo imaging of tumor senescence. In Tumor Biology 1146–1146 (American Association for Cancer Research, 2019). · DOI
  159. Krueger, M. A. et al. Abstract LB-369: In vivo imaging of tumor senescence with a novel beta-galactosidase specific PET tracer. In Tumor Biology LB-369-LB-369 (American Association for Cancer Research, 2018). · DOI
  160. Duclos, V., Iep, A., Gomez, L., Goldfarb, L. & Besson, F. L. PET molecular imaging: a holistic review of current practice and emerging perspectives for diagnosis, therapeutic evaluation and prognosis in clinical oncology. Int. J. Mol. Sci. https://doi.org/10.3390/ijms22084159 (2021). · DOI
  161. Suryadevara, V. et al. A multimodality based imaging approach using a novel radiotracer, [18f]-pygal to detect senescence in small and large animal models. Osteoarthr. Imaging 3, 100107 (2023). · DOI
  162. Odgren, P. R. et al. False-positive beta-galactosidase staining in osteoclasts by endogenous enzyme: studies in neonatal and month-old wild-type mice. Connect. Tissue Res. 47, 229–234 (2006). · DOI
  163. Kopp, H. G., Hooper, A. T., Shmelkov, S. V. & Rafii, S. Beta-galactosidase staining on bone marrow. The osteoclast pitfall. Histol. Histopathol. 22, 971–976 (2007).
  164. De Mera-Rodríguez, J. A. et al. Is senescence-associated β-galactosidase a reliable in vivo marker of cellular senescence during embryonic development? Front. Cell Dev. Biol. 9, 623175 (2021). · DOI
  165. Minami, A. et al. The function of sialidase revealed by sialidase activity imaging probe. Int. J. Mol. Sci. https://doi.org/10.3390/ijms22063187 (2021). · DOI
  166. Zhu, R., Wang, S., Xue, Z., Han, J. & Han, S. Senescence-associated sialidase revealed by an activatable fluorescence-on labeling probe. Chem. Commun. 54, 11566–11569 (2018). · DOI
  167. Hildebrand, D. G. et al. α-Fucosidase as a novel convenient biomarker for cellular senescence. Cell Cycle 12, 1922–1927 (2013). · DOI
  168. Koo, S. et al. Harnessing α-l-fucosidase for in vivo cellular senescence imaging. Chem. Sci. 12, 10054–10062 (2021). · DOI
  169. Baker, A. G. et al. An indocyanine green-based nanoprobe for in vivo detection of cellular senescence. Angew. Chem. Int. Ed. 63, e202404885 (2024). · DOI
  170. Rossi, M. & Abdelmohsen, K. The emergence of senescent surface biomarkers as senotherapeutic targets. Cells 10, 1740 (2021). · DOI · Paper page
  171. Althubiti, M. et al. Characterization of novel markers of senescence and their prognostic potential in cancer. Cell Death Dis. 5, e1528 (2014). · DOI · Paper page
  172. Ekpenyong-Akiba, A. E. et al. Detecting and targeting senescent cells using molecularly imprinted nanoparticles. Nanoscale Horiz. 4, 757–768 (2019). · DOI
  173. Poblocka, M. et al. Targeted clearance of senescent cells using an antibody-drug conjugate against a specific membrane marker. Sci. Rep. 11, 20358 (2021). · DOI · Paper page
  174. Li, S. et al. Chiral Cux Coy S nanoparticles under magnetic field and NIR light to eliminate senescent. Cells Angew. Chem. Int. Ed. 59, 13915–13922 (2020). · DOI
  175. Qu, A. et al. An NIR-responsive DNA-mediated nanotetrahedron enhances the clearance of senescent cells. Adv. Mater. 32, e2000184 (2020). · DOI
  176. Wang, H., Liu, B. & Wei, J. Beta2-microglobulin(B2M) in cancer immunotherapies: biological function, resistance and remedy. Cancer Lett. 517, 96–104 (2021). · DOI
  177. Ondruššek, R. et al. Prognostic value and multifaceted roles of tetraspanin CD9 in cancer. Front. Oncol. 13, 1140738 (2023). · DOI
  178. Nishida, M. et al. Localization of CD9, an enhancer protein for proheparin-binding epidermal growth factor-like growth factor, in human atherosclerotic plaques: possible involvement of juxtacrine growth mechanism on smooth muscle cell proliferation. Arterioscler. Thromb. Vasc. Biol. 20, 1236–1243 (2000). · DOI
  179. Cho, J. H. et al. CD9 induces cellular senescence and aggravates atherosclerotic plaque formation. Cell Death Differ. 27, 2681–2696 (2020). · DOI
  180. Nguyen, H. T. et al. CD9 monoclonal antibody-conjugated PEGylated liposomes for targeted delivery of rapamycin in the treatment of cellular senescence. Nanotechnology 28, 095101 (2017). · DOI
  181. Pham, L. M. et al. Targeting and clearance of senescent foamy macrophages and senescent endothelial cells by antibody-functionalized mesoporous silica nanoparticles for alleviating aorta atherosclerosis. Biomaterials 269, 120677 (2021). · DOI
  182. Kim, T. W. et al. Identification of replicative senescence-associated genes in human umbilical vein endothelial cells by an annealing control primer system. Exp. Gerontol. 43, 286–295 (2008). · DOI
  183. Belcastro, E. et al. Fluorescent nanocarriers targeting VCAM-1 for early detection of senescent endothelial cells. Nanomedicine 34, 102379 (2021). · DOI
  184. Fairweather-Tait, S. J., Wawer, A. A., Gillings, R., Jennings, A. & Myint, P. K. Iron status in the elderly. Mech. Ageing Dev. 136–137, 22–28 (2014). · DOI · Paper page
  185. Baker, J. R. et al. Altered iron metabolism and elevated cellular senescence in COPD small airway epithelial cells. In Airway cell biology and Immunopathology 3707 (European Respiratory Society, 2020). · DOI
  186. Amengual, J. et al. Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression. Cell Death Dis. 15, 680 (2024). · DOI
  187. Thamarath, S. S. et al. Rapid and live-cell detection of senescence in mesenchymal stem cells by micro magnetic resonance relaxometry. Stem Cells Transl. Med. 12, 266–280 (2023). · DOI
  188. Lewinska, A. et al. AMPK-mediated senolytic and senostatic activity of quercetin surface functionalized Fe3O4 nanoparticles during oxidant-induced senescence in human fibroblasts. Redox Biol. 28, 101337 (2020). · DOI
  189. Evangelou, K. & Gorgoulis, V. G. Sudan black B, the specific histochemical stain for lipofuscin: a novel method to detect senescent cells. Methods Mol. Biol. 1534, 111–119 (2017). · DOI · Paper page
  190. Jung, T., Bader, N. & Grune, T. Lipofuscin: formation, distribution, and metabolic consequences. Ann. N. Y. Acad. Sci. 1119, 97–111 (2007). · DOI · Paper page
  191. Giatromanolaki, A., Kouroupi, M., Balaska, K. & Koukourakis, M. I. A novel lipofuscin-detecting marker of senescence relates with hypoxia, dysregulated autophagy and with poor prognosis in non-small-cell-lung cancer. Vivo 34, 3187–3193 (2020). · DOI
  192. Malavolta, M. et al. Simple detection of unstained live senescent cells with imaging flow cytometry. Cells 11, 2506 (2022). · DOI
  193. Bertolo, A., Baur, M., Guerrero, J., Pötzel, T. & Stoyanov, J. Autofluorescence is a reliable in vitro marker of cellular senescence in human mesenchymal stromal cells. Sci. Rep. 9, 2074 (2019). · DOI
  194. Lozano-Torres, B., Blandez, J. F., García-Fernández, A., Sancenón, F. & Martínez-Máñez, R. Lipofuscin labeling through biorthogonal strain-promoted azide-alkyne cycloaddition for the detection of senescent cells. FEBS J. 290, 1314–1325 (2023). · DOI
  195. Magkouta, S. et al. One-step rapid tracking and isolation of senescent cells in cellular systems, tissues, or animal models via GLF16. STAR Protoc. 5, 102929 (2024). · DOI
  196. Victorelli, S. et al. Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature 622, 627–636 (2023). · DOI
  197. Santin, Y., Resta, J., Parini, A. & Mialet-Perez, J. Monoamine oxidases in age-associated diseases: New perspectives for old enzymes. Ageing Res. Rev. 66, 101256 (2021). · DOI
  198. Manzella, N. et al. Monoamine oxidase-A is a novel driver of stress-induced premature senescence through inhibition of parkin-mediated mitophagy. Aging Cell 17, e12811 (2018). · DOI
  199. Wang, R., Han, X., You, J., Yu, F. & Chen, L. Ratiometric near-infrared fluorescent probe for synergistic detection of monoamine oxidase B and its contribution to oxidative stress in cell and mice aging models. Anal. Chem. 90, 4054–4061 (2018). · DOI
  200. Zhou, L. et al. A tandemly activated fluorescence probe for detecting senescent cells with improved selectivity by targeting a biomarker combination. ACS Sens. 7, 1958–1966 (2022). · DOI

200 of 345 shown

Cited by

Sorted by citations

Metadata

Authors
Mansfield, L., Ramponi, V., Gupta, K., Stevenson, T., Mathew, A. B., Barinda, A. J., Herbstein, F., & Morsli, S.
Venue
npj Aging
Publisher
Springer Science and Business Media LLC
Published
2024-11-22
Volume
10
Issue
1
ISSN
2731-6068
DOI
10.1038/s41514-024-00181-1
PMC
PMC11584693
Cited by
88
References
117
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review