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Inflammaging and Oxidative Stress: Silent Drivers of Aging

Inflammaging and Oxidative Stress: Silent Drivers of Aging
Photo by Seval Torun / Unsplash

Introduction

Aging is not only about the gradual decline of organs and tissues—it is also about the body’s internal environment. Two processes stand out as silent drivers of aging: oxidative stress and chronic low-grade inflammation (often termed inflammaging). Together, they accelerate cellular damage, disrupt repair, and increase vulnerability to age-related diseases.

1. Oxidative Stress: The Double-Edged Sword

1.1 What Is Oxidative Stress?

Oxidative stress occurs when the production of reactive oxygen species (ROS) overwhelms the body’s antioxidant defenses. While ROS play important roles in cell signaling and immune defense, excessive levels damage DNA, proteins, and lipids.

1.2 Aging and ROS

With age, mitochondrial efficiency declines and ROS production increases. At the same time, antioxidant capacity (enzymes like superoxide dismutase and glutathione peroxidase) diminishes. This imbalance drives cellular dysfunction.

1.3 Consequences

  • DNA mutations and genomic instability
  • Protein misfolding and aggregation
  • Lipid peroxidation affecting membranes
  • Contribution to cancer, cardiovascular disease, and neurodegeneration

2. Inflammaging: Chronic Low-Grade Inflammation

2.1 The Concept

First coined by Franceschi and colleagues, inflammaging refers to the persistent, systemic, low-level inflammation observed in older adults—even in the absence of infection.

2.2 Sources of Inflammaging

  • Cellular senescence: Senescent cells secrete pro-inflammatory molecules (the SASP).
  • Immunosenescence: The aging immune system shifts toward chronic activation but reduced effectiveness.
  • Metabolic dysfunction: Adipose tissue secretes inflammatory cytokines (IL-6, TNF-α).
  • Gut dysbiosis: Microbiome changes can trigger immune activation.

2.3 Consequences

Inflammaging contributes to nearly all major age-associated diseases:

  • Atherosclerosis
  • Type 2 diabetes
  • Alzheimer’s disease
  • Frailty and sarcopenia

3. The Oxidative Stress–Inflammation Feedback Loop

Oxidative stress and inflammation reinforce each other.

  • ROS activate NF-κB, a transcription factor that promotes inflammation.
  • Inflammatory cytokines increase mitochondrial ROS production.
    This creates a vicious cycle, accelerating aging and disease progression.

4. Interventions and Strategies

4.1 Lifestyle Approaches

  • Exercise: Regular moderate activity reduces inflammation and improves antioxidant defenses.
  • Diet: Mediterranean and plant-rich diets provide antioxidants and anti-inflammatory compounds.
  • Sleep: Restorative sleep regulates immune and oxidative balance.
  • Stress management: Chronic psychological stress raises cortisol and inflammatory cytokines.

4.2 Nutritional Compounds

  • Omega-3 fatty acids (EPA, DHA) dampen inflammation.
  • Polyphenols (resveratrol, quercetin, curcumin) act as mild stressors, boosting antioxidant defense.
  • Glycine and N-acetylcysteine (NAC) support glutathione production.

4.3 Medical and Experimental Approaches

  • Senolytics: Drugs that selectively remove senescent cells.
  • Metformin: Shows anti-inflammatory and antioxidant effects beyond glucose control.
  • mTOR inhibitors (rapamycin): May reduce pro-inflammatory signaling and extend lifespan in animal models.

Conclusion

Inflammaging and oxidative stress are not inevitable fates—they are modifiable risk factors. By targeting the vicious cycle between ROS and chronic inflammation, it may be possible to delay the onset of age-related diseases and extend healthspan. Lifestyle choices remain the most effective tools, but emerging therapies promise to complement these efforts.

References

  • Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4–S9.
  • Liguori I, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757–772.
  • López-Otín C, et al. The hallmarks of aging. Cell. 2013;153(6):1194–1217.
  • Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15(9):505–522.
  • Finkel T, Holbrook NJ. Oxidants, oxidative stress, and the biology of ageing. Nature. 2000;408(6809):239–247.
  • Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms, and clinical relevance. Biochim Biophys Acta. 2015;1851(4):469–484.