Cellular and Molecular Life Sciences

, Volume 69, Issue 18, pp 2999–3013 | Cite as

Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases

  • Antero Salminen
  • Johanna Ojala
  • Kai Kaarniranta
  • Anu Kauppinen


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.


Ageing Autophagy Inflammasome Inflammation NF-κB NLRP3 



Absent in melanoma 2


Apoptosis-associated speck-like protein containing CARD domain


Caspase recruitment domain


Cerebrospinal fluid


Damage-associated molecular pattern


Double-stranded DNA


Endoplasmic reticulum


Formyl peptide receptor


High-mobility group protein B1


Islet amyloid polypeptide


Interferon β


Inhibitory-κB kinase






Leucine-rich repeat


Mitochondria-associated ER membrane


Mitochondrial antiviral signaling protein


Mitochondrial manganese superoxide dismutase


Mitochondrial DNA


Nicotinamide adenine dinucleotide phosphate


Nuclear factor-κB


NLR family, apoptosis inhibitory protein


Nucleotide-binding domain leucine-rich repeat-containing receptor family


NLR family, CARD-containing 4


NLR family, pyrin domain-containing 3


Nucleotide-binding oligomerization domain-containing protein 1


Nitric-oxide synthase


NADPH oxidases 1–4


Nuclear factor E2-related factor 2


P2X purinoceptor 7


Polymorphonuclear neutrophil


Pyrin domain


Retinoic acid inducible gene-1


Reactive oxygen species


Senescence-accelerated prone mouse


Signal transducer and activator of transcription 1


Toll-like receptors


Tumour necrosis factor


TNF receptor-associated factor


Tripartite-motif protein 30




Thioredoxin-interacting protein


Uncoupling protein


Mitochondrial unfolded protein response


Ultraviolet B



This study was financially supported by Grants from the Academy of Finland and the University of Eastern Finland, Kuopio, Finland. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.


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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Antero Salminen
    • 1
    • 2
  • Johanna Ojala
    • 1
  • Kai Kaarniranta
    • 3
    • 4
  • Anu Kauppinen
    • 3
  1. 1.Department of Neurology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of NeurologyUniversity Hospital of KuopioKuopioFinland
  3. 3.Department of Ophthalmology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  4. 4.Department of OphthalmologyUniversity Hospital of KuopioKuopioFinland

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