Childs, B. G. et al. Senescent cells: an emerging target for diseases of ageing. Nat. Rev. Drug Discov. 16, 718–735 (2017).
Kang, T. W. et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547–551 (2011).
Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008).
Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012).
Johmura, Y. et al. Necessary and sufficient role for a mitosis skip in senescence induction. Mol. Cell 55, 73–84 (2014).
Pieren, D. K. J., Smits, N. A. M., van de Garde, M. D. B. & Guichelaar, T. Response kinetics reveal novel features of ageing in murine T cells. Sci. Rep. 9, 5587 (2019).
Lages, C. S., Lewkowich, I., Sproles, A., Wills-Karp, M. & Chougnet, C. Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/PD-L1 pathway. Aging Cell 9, 785–798 (2010).
Channappanavar, R., Twardy, B. S., Krishna, P. & Suvas, S. Advancing age leads to predominance of inhibitory receptor expressing CD4 T cells. Mech. Ageing Dev. 130, 709–712 (2009).
Decman, V. et al. Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursors. J. Immunol. 188, 1933–1941 (2012).
Omori, S. et al. Generation of a p16 reporter mouse and its use to characterize and target p16high cells in vivo. Cell Metab. 32, 814–828.e6 (2020).
Sadasivam, S. & DeCaprio, J. A. The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nat. Rev. Cancer 13, 585–595 (2013).
Helmbold, H., Kömm, N., Deppert, W. & Bohn, W. Rb2/p130 is the dominating pocket protein in the p53–p21 DNA damage response pathway leading to senescence. Oncogene 28, 3456–3467 (2009).
Fan, J. & Bertino, J. R. Functional roles of E2F in cell cycle regulation. Oncogene 14, 1191–1200 (1997).
Dyson, N., Guida, P., Münger, K. & Harlow, E. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J. Virol. 66, 6893–6902 (1992).
Janky, R. et al. iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLoS Comput. Biol. 10, e1003731 (2014).
Verfaillie, A., Imrichova, H., Janky, R. & Aerts, S. iRegulon and i-cisTarget: reconstructing regulatory networks using motif and track enrichment. Curr. Protoc. Bioinformatics 52, 2 (2015).
Zhang, J. et al. Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 553, 91–95 (2018).
Lim, S. O. et al. Deubiquitination and stabilization of PD-L1 by CSN5. Cancer Cell 30, 925–939 (2016).
Rechsteiner, M. & Hill, C. P. Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors. Trends Cell Biol. 15, 27–33 (2005).
Radhakrishnan, S. K. et al. Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol. Cell 38, 17–28 (2010).
Zhang, Y. & Hayes, J. D. The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity. Sci. Rep. 3, 2006 (2013).
Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11, 973–979 (2009).
Muñoz-Espín, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. 15, 482–496 (2014).
Griffin, G. K. et al. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity. Nature 595, 309–314 (2021).
Zhang, S. M. et al. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 598, 682–687 (2021).
Kalbasi, A. et al. Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma. Sci. Transl. Med. 12, eabb0152 (2020).
Grosse, L. et al. Defined p16High senescent cell types are indispensable for mouse healthspan. Cell Metab. 32, 87–99.e6 (2020).
Maeso-Díaz, R. et al. Effects of aging on liver microcirculatory function and sinusoidal phenotype. Aging Cell 17, e12829 (2018).
Vaddepally, R. K., Kharel, P., Pandey, R., Garje, R. & Chandra, A. B. Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers 12, 738 (2020).
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).
Schulte, H., Mühlfeld, C. & Brandenberger, C. Age-related structural and functional changes in the mouse lung. Front. Physiol. 10, 1466 (2019).
Gregg, S. Q. et al. A mouse model of accelerated liver aging caused by a defect in DNA repair. Hepatology 55, 609–621 (2012).
Sheth, K. A. et al. Muscle strength and size are associated with motor unit connectivity in aged mice. Neurobiol. Aging 67, 128–136 (2018).
Tung, V. W. K., Burton, T. J., Quail, S. L., Mathews, M. A. & Camp, A. J. Motor performance is impaired following vestibular stimulation in ageing mice. Front. Aging Neurosci. 8, 12 (2016).
Ogrodnik, M. et al. Cellular senescence drives age-dependent hepatic steatosis. Nat. Commun. 8, 15691 (2017).
Matsumoto, M. et al. An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. Int. J. Exp. Pathol. 94, 93–103 (2013).
Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22, 78–83 (2016).
Kazankov, K. et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat. Rev. Gastroenterol. Hepatol. 16, 145–159 (2019).
Gate, D. et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature 577, 399–404 (2020).
Hashimoto, K. et al. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians. Proc. Natl Acad. Sci. USA 116, 24242–24251 (2019).
McDonnell, W. J. et al. High CD8 T-cell receptor clonality and altered CDR3 properties are associated with elevated isolevuglandins in adipose tissue during diet-induced obesity. Diabetes 67, 2361–2376 (2018).
Koda, Y. et al. CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells. Nat. Commun. 12, 4474 (2021).
Baruch, K. et al. PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer’s disease. Nat. Med. 22, 135–137 (2016).
Rosenzweig, N. et al. PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model. Nat. Commun. 10, 465 (2019).
Pfister, D. et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 592, 450–456 (2021).
Martins, F. et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat. Rev. Clin. Oncol. 16, 563–580 (2019).
Kondo, T. et al. Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy. Nat. Commun. 8, 15338 (2017).
Hogquist, K. A. et al. T cell receptor antagonist peptides induce positive selection. Cell 76, 17–27 (1994).
Simma, O. et al. Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance. Cancer Res. 69, 203–211 (2009).
Merry, T. L. et al. The CSF1 receptor inhibitor pexidartinib (PLX3397) reduces tissue macrophage levels without affecting glucose homeostasis in mice. Int. J. Obesity 44, 245–253 (2020).
Nakanishi, M. et al. Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA. Proc. Natl Acad. Sci. USA 92, 4352–4356 (1995).
Parrinello, S. et al. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat. Cell Biol. 5, 741–747 (2003).
Johmura, Y. et al. SCFFbxo22-KDM4A targets methylated p53 for degradation and regulates senescence. Nat. Commun. 7, 10574 (2016).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Anders, S., Pyl, P. T. & Huber, W. HTSeq-A Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Liao, Y., Smyth, G. K. & Shi, W. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads. Nucleic Acids Res. 47, e47 (2019).
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2009).
Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
Yu, G., Wang, L. G., Han, Y. & He, Q. Y. ClusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012).
Storer, J., Hubley, R., Rosen, J., Wheeler, T. J. & Smit, A. F. The Dfam community resource of transposable element families, sequence models, and genome annotations. Mob. DNA 12, 2 (2021).
Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: Large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).
Lewis, M. D. et al. A reproducible method for the expansion of mouse CD8+ T lymphocytes. J. Immunol. Methods 417, 134–138 (2015).
Kitamura, T., Doughty-Shenton, D., Pollard, J. W. & Carragher, N. O. Real time detection of in vitro tumor cell apoptosis induced by CD8+ T cells to study immune suppressive functions of tumor-infiltrating myeloid cells. J. Vis. Exp. https://doi.org/10.3791/58841 (2019).
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