Abstract
Almost a half century ago, the free radical theory of ageing proposed that the reactive oxygen species (ROS) is a key component which contributes to the pathophysiology of ageing in mammalian cells. Over the years, numerous studies have documented the role of oxidative stress caused by ROS in the ageing process of higher organisms. In particular, several age-associated disease models suggest that ROS and oxidative stress modulate the incidence of age-related pathologies, and that it can strongly influence the ageing process and possibly lifespan. The exact mechanism of ROS and oxidative stress-induced age-related pathologies is not yet very clear. Damage to biological macromolecules caused by ROS is thought to result in many age-related chronic diseases. At the cellular level, increased ROS leads to cellular senescence among other cellular fates including apoptosis, necrosis and autophagy. Cellular senescence is a stable growth arrest phase of cells characterized by the secretion of senescence-associated secretory phenotype (SASP) factors. Recent evidence suggests that cellular senescence via its growth arrest phenotype and SASP factors is a strong contributing factor in the development of age-associated diseases. In addition, we suggest that SASP factors play an important role in the maintenance of age-associated pathologies via a positive feedback mechanism. This review aims to provide an overview of ROS mechanics and its possible role in the ageing process via induction of cellular senescence.
Highlights
Ageing is a natural process that all living beings experience over the course of their lifetimes
The free radical theory of ageing (FRTA) is not a perfect theory of ageing and age-related diseases, it provides a basic platform to address the potential role of oxidative stress and reactive oxygen species (ROS) generated by various stresses that an organism encounter during its lifespan
The mitohormosis stipulates that a balanced ROS may function as signaling molecules that contribute to longevity by instigating an adaptive response
Summary
Ageing is a natural process that all living beings experience over the course of their lifetimes. The theory was later refined by Harman himself to emphasize the role of mitochondrial ROS, as the majority of free radical oxygen species (ROS) production originates in the mitochondria of mammalian cells, and was termed as the mitochondrial theory of ageing [2]. The excess ROS in a cell can lead to four different cellular fates or phenotypes- apoptosis, necrosis, autophagy and senescence. These cellular fates, in general have negative consequences to a normal cellular and tissue homeostasis, which eventually lead to the development of age-associated pathologies at the organismic level and can adversely impact life span of an organism. We briefly discuss the different sources and defenses of ROS, and examine ROS-induced cellular fates, in particular cellular senescence, which can accelerate various age-related pathologies and diseases such as cancer, cardiovascular and neurodegenerative diseases
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