Novel insights into ferroptosis: Implications for age-related diseases

Theranostics. 2020 Oct 26;10(26):11976-11997. doi: 10.7150/thno.50663. eCollection 2020.

Abstract

Rapid increase in aging populations is an urgent problem because older adults are more likely to suffer from disabilities and age-related diseases (ARDs), burdening healthcare systems and society in general. ARDs are characterized by the progressive deterioration of tissues and organs over time, eventually leading to tissue and organ failure. To date, there are no effective interventions to prevent the progression of ARDs. Hence, there is an urgent need for new treatment strategies. Ferroptosis, an iron-dependent cell death, is linked to normal development and homeostasis. Accumulating evidence, however, has highlighted crucial roles for ferroptosis in ARDs, including neurodegenerative and cardiovascular diseases. In this review, we a) summarize initiation, regulatory mechanisms, and molecular signaling pathways involved in ferroptosis, b) discuss the direct and indirect involvement of the activation and/or inhibition of ferroptosis in the pathogenesis of some important diseases, and c) highlight therapeutic targets relevant for ARDs.

Keywords: age-related diseases; ferroptosis; iron; lipid peroxidation; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / drug effects
  • Aging / pathology*
  • Animals
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / pathology
  • Cell Line, Tumor
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / pathology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Ferroptosis / drug effects*
  • Ferroptosis / physiology
  • Humans
  • Iron / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / pathology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Iron