Implication of ferroptosis in aging

Abstract

Life is indeed continuously going through the irreversible and inevitable process of aging. The rate of aging process depends on various factors and varies individually. These factors include various environmental stimuli including exposure to toxic chemicals, psychological stress whereas suffering with various illnesses specially the chronic diseases serve as endogenous triggers. The basic underlying mechanism for all kinds of stresses is now known to be manifested as production of excessive ROS, exhaustion of ROS neutralizing antioxidant enzymes and proteins leading to imbalance in oxidation and antioxidant processes with subsequent oxidative stress induced inflammation affecting the cells, tissues, organs and the whole body. All these factors lead to conventional cell death either through necrosis, apoptosis, or autophagy. Currently, a newly identified mechanism of iron dependent regulated cell death called ferroptosis, is of special interest for its implication in pathogenesis of various diseases such as cardiovascular disease, neurological disorders, cancers, and various other age-related disorders (ARD). In ferroptosis, the cell death occur neither by conventional apoptosis, necrosis nor by autophagy, rather dysregulated iron in the cell mediates excessive lipid peroxidation of accumulated lethal lipids. It is not surprising to assume its role in aging as previous research have identified some solid cues on the subject. In this review, we will highlight the factual evidences to support the possible role and implication of ferroptosis in aging in order to declare the need to identify and explore the interventions to prevent excessive ferroptosis leading to accelerated aging and associated liabilities of aging.

Ferroptosis Mechanisms Involved in Hippocampal-Related Diseases

“…With increasing age, the permeability of the BBB increases, inflammation occurs, iron is redistributed in the brain, and changes in iron homeostasis occur that all lead to the continuous accumulation of iron in the brain. However, studies have found significant ferroptosis in the brains of older people [104]. These suggest that ferroptosis is closely related to the pathological changes associated with aging.…”

Hydrogen Sulfide Biology and Its Role in Cancer

“…Ferroptosis is a type of cell death that is caused by cell membrane damage, via glutathione peroxidase (GPX) activity failure and intracellular lipid peroxide, which is accompanied by iron-dependent reactive oxygen species production (ROS) [ 208 , 209 ]. Its physiology, genetics, and biochemical properties are distinct from apoptosis, necrosis, autophagy, and pyroptosis [ 210 ].…”

Ferroptosis and Its Potential Role in the Nervous System Diseases

“…107 Ferroptosis is also involved in aging and neurodegeneration. [108][109][110] Iron is excessive with aging. 108 The reasons for this are the following: (i) the body's metabolic rate decreases with aging, resulting in a decrease in iron requirements and an increase in iron accumulation; (ii) the amount of hemoglobin that stores 60% of total iron decreases with aging; and (iii) menopause causes relative iron excess in women.…”