Mitochondrial Dysfunction and Oxidative Stress Activate Inflammasomes: Impact on the Aging Process and Age-related Diseases

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2012 Mar 27

PMID 22446749

Citations 122

Authors

Antero Salminen

Johanna Ojala

Kai Kaarniranta

Anu Kauppinen

Affiliations

Soon will be listed here.

Abstract

Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1β and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-κB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases.

Citing Articles

Aging, vascular dysfunction, and the blood-brain barrier: unveiling the pathophysiology of stroke in older adults.

Alaqel S, Imran M, Khan A, Nayeem N Biogerontology. 2025; 26(2):67.

PMID: 40044939 DOI: 10.1007/s10522-025-10209-y.

GDF15/MIC-1: a stress-induced immunosuppressive factor which promotes the aging process.

Salminen A Biogerontology. 2024; 26(1):19.

PMID: 39643709 PMC: 11624233. DOI: 10.1007/s10522-024-10164-0.

Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats dependent on NLRP3 activation.

Bonfante S, Netto M, de Oliveira Junior A, Mathias K, Machado R, Joaquim L Metab Brain Dis. 2024; 40(1):1.

PMID: 39535569 DOI: 10.1007/s11011-024-01425-5.

Serum proteomics study on cognitive impairment after cardiac valve replacement surgery: a prospective observational study.

Ma H, Wei Y, Chen W, Chen S, Wang Y, Cao S PeerJ. 2024; 12:e17536.

PMID: 38912047 PMC: 11192023. DOI: 10.7717/peerj.17536.

Roundup induces premature senescence of mouse granulosa cells via mitochondrial ROS-triggered NLRP3 inflammasome activation.

Ni H, Hu X, Yang N, Liu X, Cai W, Zhong R Toxicol Res. 2024; 40(3):377-387.

PMID: 38911547 PMC: 11187041. DOI: 10.1007/s43188-024-00229-0.

References

Kaimul A, Nakamura H, Masutani H, Yodoi J . Thioredoxin and thioredoxin-binding protein-2 in cancer and metabolic syndrome. Free Radic Biol Med. 2007; 43(6):861-8. DOI: 10.1016/j.freeradbiomed.2007.05.032. View

Csiszar A, Ungvari Z, Koller A, Edwards J, Kaley G . Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. FASEB J. 2003; 17(9):1183-5. DOI: 10.1096/fj.02-1049fje. View

Lunov O, Syrovets T, Loos C, Nienhaus G, Mailander V, Landfester K . Amino-functionalized polystyrene nanoparticles activate the NLRP3 inflammasome in human macrophages. ACS Nano. 2011; 5(12):9648-57. DOI: 10.1021/nn203596e. View

Swindell W . Genes and gene expression modules associated with caloric restriction and aging in the laboratory mouse. BMC Genomics. 2009; 10:585. PMC: 2795771. DOI: 10.1186/1471-2164-10-585. View

Alboni S, Cervia D, Sugama S, Conti B . Interleukin 18 in the CNS. J Neuroinflammation. 2010; 7:9. PMC: 2830964. DOI: 10.1186/1742-2094-7-9. View

Menu P, Mayor A, Zhou R, Tardivel A, Ichijo H, Mori K . ER stress activates the NLRP3 inflammasome via an UPR-independent pathway. Cell Death Dis. 2012; 3:e261. PMC: 3270266. DOI: 10.1038/cddis.2011.132. View

Fesus L, Demeny M, Petrovski G . Autophagy shapes inflammation. Antioxid Redox Signal. 2010; 14(11):2233-43. DOI: 10.1089/ars.2010.3485. View

Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer H . The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007; 17(13):1140-5. DOI: 10.1016/j.cub.2007.05.074. View

van Bruggen R, Koker M, Jansen M, Van Houdt M, Roos D, Kuijpers T . Human NLRP3 inflammasome activation is Nox1-4 independent. Blood. 2010; 115(26):5398-400. DOI: 10.1182/blood-2009-10-250803. View

10.

Dinarello C . Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr. 2006; 83(2):447S-455S. DOI: 10.1093/ajcn/83.2.447S. View

11.

Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S . Mite allergen is a danger signal for the skin via activation of inflammasome in keratinocytes. J Allergy Clin Immunol. 2011; 127(3):806-14.e1-4. DOI: 10.1016/j.jaci.2010.12.006. View

12.

Kowaltowski A, de Souza-Pinto N, Castilho R, Vercesi A . Mitochondria and reactive oxygen species. Free Radic Biol Med. 2009; 47(4):333-43. DOI: 10.1016/j.freeradbiomed.2009.05.004. View

13.

Weiskopf D, Weinberger B, Grubeck-Loebenstein B . The aging of the immune system. Transpl Int. 2009; 22(11):1041-50. DOI: 10.1111/j.1432-2277.2009.00927.x. View

14.

Stoltzman C, Peterson C, Breen K, Muoio D, Billin A, Ayer D . Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression. Proc Natl Acad Sci U S A. 2008; 105(19):6912-7. PMC: 2383952. DOI: 10.1073/pnas.0712199105. View

15.

Bruunsgaard H, Andersen-Ranberg K, Hjelmborg J, Pedersen B, Jeune B . Elevated levels of tumor necrosis factor alpha and mortality in centenarians. Am J Med. 2003; 115(4):278-83. DOI: 10.1016/s0002-9343(03)00329-2. View

16.

Ojala J, Alafuzoff I, Herukka S, van Groen T, Tanila H, Pirttila T . Expression of interleukin-18 is increased in the brains of Alzheimer's disease patients. Neurobiol Aging. 2007; 30(2):198-209. DOI: 10.1016/j.neurobiolaging.2007.06.006. View

17.

Harman D . Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956; 11(3):298-300. DOI: 10.1093/geronj/11.3.298. View

18.

Masters S, Dunne A, Subramanian S, Hull R, Tannahill G, Sharp F . Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat Immunol. 2010; 11(10):897-904. PMC: 3103663. DOI: 10.1038/ni.1935. View

19.

Trifunovic A, Larsson N . Mitochondrial dysfunction as a cause of ageing. J Intern Med. 2008; 263(2):167-78. DOI: 10.1111/j.1365-2796.2007.01905.x. View

20.

Salminen A, Ojala J, Suuronen T, Kaarniranta K, Kauppinen A . Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer's pathology. J Cell Mol Med. 2008; 12(6A):2255-62. PMC: 4514104. DOI: 10.1111/j.1582-4934.2008.00496.x. View