Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

By D. Jurk, Caroline L. Wilson, J. Passos, F. Oakley, C. Correia-Melo, Laura C. Greaves, G. Saretzki, C. Fox, Conor Lawless, Rhys K. Anderson and 8 more. Nature Communications, 2014

771 citations recorded by the source corpus.

Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-κB induces premature ageing in mice. We also show that these mice have reduced regeneration in liver and gut. nfkb1−/− fibroblasts exhibit aggravated cell senescence because of an enhanced autocrine and paracrine feedback through NF-κB, COX-2 and ROS, which stabilizes DNA damage. Preferential accumulation of telomere-dysfunctional senescent cells in nfkb1−/− tissues is blocked by anti-inflammatory or antioxidant treatment of mice, and this rescues tissue regenerative potential. Frequencies of senescent cells in liver and intestinal crypts quantitatively predict mean and maximum lifespan in both short- and long-lived mice cohorts. These data indicate that systemic chronic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence in the absence of any other genetic or environmental factor. Many age-related diseases are associated with chronic inflammation. Here Jurk et al. use a mouse model of chronic, low-grade inflammation to support a model by which such inflammation promotes a vicious cycle of oxidative stress, telomere dysfunction and cell senescence that accelerates the ageing process.

Subfields: Aging, Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/af8cbc5823ef402bcf34c4b90e744f65bb0fc3c0

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. J. Campisi
2. J. Kirkland
3. T. Tchkonia
4. M. Demaria
5. Manuel Serrano
6. J. Passos
7. V. Krizhanovsky
8. M. Collado

In Immunology

1. J. Campisi
2. J. Kirkland
3. T. Tchkonia
4. M. Demaria
5. Claudio Franceschi
6. Manuel Serrano
7. V. Krizhanovsky
8. P. Jat

In Physiology

1. J. Campisi
2. J. Kirkland
3. T. Tchkonia
4. M. Demaria
5. Manuel Serrano
6. P. Jat
7. R. Kumari
8. M. Collado

Citations in the corpus

• Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021, background): “Multiple studies have shown that most of the age-related pathologies stem from low level chronic inflammation referred to as inflammaging or sterile inflammation which can also result in premature aging (Franceschi et al., 2007; Chung et al., 2009; Franceschi and Campisi, 2014; Jurk et al., 2014).”
• Mitochondrial dysfunction in cell senescence and aging (2022, background): “Senescent cells accumulate with aging in many mammalian and non-mammalian tissues (8), and intervention experiments (9–11) have proven that this accumulation is a physiologically important driver of age-associated functional decline, (multi-)morbidity, and mortality (for review, see ref.”
• Inflammaging and 'Garb-aging'. (2017, background): “Moreover, systemic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence, in the absence of any other genetic or environmental factor [69].”
• Cellular Senescence: Defining a Path Forward. (2019, background): “Furthermore, these mice show increased incidence of senescent cells in multiple tissues (Jurk et al., 2014).”
• Mechanisms and functions of cellular senescence. (2018, neutral): “However, terminally differentiated cells such as neurons, adipocytes, and hepatocytes can also undergo senescence, or at least show senescence-like features, during aging or in response to oncogenic activation or DNA damage (21, 23–25).”
• Cellular Senescence: A Translational Perspective (2017, background): “Furthermore, a linear association between senescent cell burden and mean and maximum lifespan over a wide range of ages has been demonstrated in mice (Jurk et al., 2014).”
• Inflammation and aging: signaling pathways and intervention therapies (2023, background): “Interestingly, the accumulation of senescent cells with telomere-dysfunction in Nfkb1−/− tissues can be effectively hindered through the implementation of antiinflammatory or antioxidant treatment in mice.(303) This noteworthy observation underscores the promising utilization of these mice as Table ”