Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

Chung, H. Y. et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev. 8, 18–30 (2009).

Franceschi, C. et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128, 92–105 (2007).

Zhang, G. et al. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature 497, 211–216 (2013).

Adler, A. S. et al. Motif module map reveals enforcement of aging by continual NF-kB activity. Genes Dev. 21, 3244–3257 (2007).

Kawahara, T. L. A. et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell 136, 62–74 (2009).

Osorio, F. G. et al. Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response. Genes Dev. 26, 2311–2324 (2012).

Tilstra, J. S. et al. NF-κB inhibition delays DNA damage–induced senescence and aging in mice. Clin. Invest. 122, 2601–2612 (2012).

Martin, G. M., Bergman, A. & Barzilai, N. Genetic determinants of human health span and life span: progress and new opportunities. PLoS Genet. 3, e125 (2007).

d’Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003).

Choudhury, A. R. et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat. Genet. 39, 99–105 (2007).

Hewitt, G. et al. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat Commun. 3, 708 (2012).

Passos, J. F. et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol. Syst. Biol. 6, 347 (2010).

Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019–1031 (2008).

Acosta, J. C. et al. Chemokine signalling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018 (2008).

Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11, 973–979 (2009).

Chien, Y. et al. Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. Genes Dev. 25, 2125–2136 (2011).

Freund, A., Patil, C. K. & Campisi, J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 30, 1536–1548 (2011).

Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011).

Salminen, A. et al. Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging. Ageing Res. Rev. 7, 83–105 (2008).

Elsharkawy, A. M. et al. The NF-κB p50:p50:HDAC-1 repressor complex orchestrates transcriptional inhibition of multiple pro-inflammatory genes. Hepatology 53, 519–527 (2010).

Oakley, F. et al. Nuclear factor-κB1 (p50) limits the inflammatory and fibrogenic responses to chronic injury. Am. J. Pathol. 166, 695–708 (2005).

Mizgerd, J. P. et al. Nuclear factor-κB p50 limits inflammation and prevents lung injury during Escherichia coli pneumonia. Am. Respir. Crit. Care Med. 168, 810–817 (2003).

Campbell, S. et al. Hepatic nuclear factor kappa B regulates neutrophil recruitment to the injured brain. J. Neuropathol. Exp. Neurol. 67, 223–230 (2008).

Liao, C. Y. et al. Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell 10, 629–639 (2011).

Baud, V. & Karin, M. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat. Rev. Drug Discov. 8, 33–40 (2009).

Krupczak-Hollis, K., Wang, X., Dennewitz, M. B. & Costa, R. H. Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b. Hepatology 38, 1552–1562 (2003).

Kauppinen, A., Suuronen, T., Ojala, J., Kaarniranta, K. & Salminen, A. Antagonistic crosstalk between NF-kappaB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell. Signal. 25, 1939–1948 (2013).

Chen, T. S., Currier, G. J. & Wabner, C. L. Intestinal transport during the lifespan of the mouse. J. Gerontol. Biol. Sci. 45, B129–B133 (1990).

Parrinello, S. et al. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat. Cell Biol. 5, 741–747 (2003).

Coppe, J.-P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, e301 (2008).

Miyamoto, S. Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage. Cell Res. 21, 116–130 (2010).

Freund, A., Orjalo, A. V., Desprez, P. Y. & Campisi, J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med. 16, 238–246 (2010).

Sahin, E. et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 470, 359–365 (2011).

Rainsford, K. D. Anti-inflammatory drugs in the 21st century. Subcell. Biochem. 42, 3–27 (2007).

Martien, S. et al. Cellular senescence involves an intracrine prostaglandin E2 pathway in human fibroblasts. Biochim. Biophys. Acta Mol, Cell Biol. Lipids 1831, 1217–1227 (2013).

Nelson, G. et al. A senescent cell bystander effect: senescence-induced senescence. Aging Cell 11, 345–349 (2012).

Acosta, J. C. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15, 978–990 (2013).

Shay, J. W. & Wright, W. E. Roles of telomeres and telomerase in cancer. Semin. Cancer Biol. 21, 349–353 (2011).

Fumagalli, M. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 14, 355–365 (2012).

Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J. M. Cellular Senescence in Aging Primates. Science 311, 1257 (2006).

Salama, R., Sadaie, M., Hoare, M. & Narita, M. Cellular senescence and its effector programs. Genes Dev. 28, 99–114 (2014).

Lawless, C. et al. Quantitative assessment of markers for cell senescence. Exp. Gerontol. 45, 772–778 (2010).

Wang, C., Jurk, D., Nelson, G., Martin-Ruiz, C. & von Zglinicki, T. DNA damage response and cellular senescence in aging mice. Aging Cell 8, 311–323 (2009).

Lee, Y. J. & Chuang, Y. C. Ibuprofen augments pro-inflammatory cytokine release in a mouse model of Vibrio vulnificus infection. Microbiol. Immunol. 54, 542–550 (2010).

Teeling, J. L., Cunningham, C., Newman, T. A. & Perry, V. H. The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: Implications for a role of COX-1. Brain Behav. Immun. 24, 409–419 (2009).

Aparicio-Vergara, M. et al. TNF receptor 1 gain-of-function mutation aggravates non-alcoholic fatty liver disease but does not cause insulin resistance in a murine model. Hepatology 57, 566–576 (2013).

Ghosh, A. et al. Telomerase directly regulates NF-kappaB-dependent transcription. Nat. Cell Biol. 14, 1270–1281 (2012).

von Zglinicki, T. Oxidative stress shortens telomeres. Trends Biochem. Sci. 27, 339–344 (2002).

Jurk, D. et al. Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell 11, 996–1004 (2012).

Sperka, T. et al. Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction. Nat. Cell Biol. 14, 73–79 (2012).

Rossi, D. J. et al. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447, 725–729 (2007).

Wang, J. et al. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell 148, 1001–1014 (2012).

Rhee, D. B., Ghosh, A., Lu, J., Bohr, V. A. & Liu, Y. Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1. DNA Repair (Amst) 10, 34–44 (2011).

Petersen, S., Saretzki, G. & von Zglinicki, T. Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. Exp. Cell Res. 239, 152–160 (1998).

Passos, J. F. et al. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol. 5, e110 (2007).

Strong, R. et al. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7, 641–650 (2008).

Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J. & Kirkland, J. L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest. 123, 966–972 (2013).

Hillege, H. L. et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113, 671–678 (2006).

Fontana, L. et al. Identification of a metabolic signature for multidimensional impairment and mortality risk in hospitalized older patients. Aging Cell 12, 459–466 (2013).

Collerton, J. et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech. Ageing Dev. 133, 456–466 (2012).

Cameron, K. M., Miwa, S., Walker, C. & von Zglinicki, T. Male mice retain a metabolic memory of improved glucose tolerance induced during adult onset, short-term dietary restriction. Longevity Healthspan 1, 3 (2012).

Cameron, K. M. et al. Gross energy metabolism in mice under late onset, short term caloric restriction. Mech. Ageing Dev. 132, 202–209 (2011).

Higgins, G. & Anderson, R. Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 12, 186–202 (1931).

Tomas-Loba, A. et al. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135, 609–622 (2008).

Nelson, G., Buhmann, M. & von Zglinicki, T. DNA damage foci in mitosis are devoid of 53BP1. Cell Cycle 8, 3379–3383 (2009).

Sato, H. et al. Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation. Biochem J. 421, 17–27 (2009).

Ullman-Cullere, M. & Foltz, C. Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab. Anim. Sci. 49, 319–323 (1999).

Hawkins, P. et al. A guide to defining and implementing protocols for the welfare assessment of laboratory animals: eleventh report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on refinement. Lab. Anim. 45, 1–13 (2011).