The Role of Reactive Oxygen Species in Aging is Complex

Every compound and aspect of biology has a dose-response relationship of some sort. Wildly different outcomes should be expected at different levels of a drug, different degrees of expression of a protein, differing activity of a signaling pathway. What is a beneficial therapy at one dose is a toxin at another. A great many toxic substances and ostensibly harmful processes that damage the mechanisms of a cell are in fact beneficial at low doses, thanks to the hormetic response. A cell senses damage and engages a greater activity of its repair and maintenance processes, such as autophagy. The result is a net gain in cell maintenance. A mild stress, repeated infrequently, can improve cell function, tissue function, and, as a consequence, overall health and life span.

This underlies much of the observed complexity of the interaction between oxidative molecules and aging. In old age, there is an excess of oxidative molecules, reactive oxygen species, as a result of mitochondrial dysfunction, chronic inflammation, and other issues that provoke a greater generation of oxidative stress. This is harmful, it is past the point at which any benefit occurs. Interventions that greatly increase oxidative stress in animal models shorten life span. But there are many examples of genetic alterations in short-lived species in which a mild increase in the output of reactive oxygen species by mitochondria results in a gain in life span. Similarly, many of the metabolic improvements of exercise are provoked by raised mitochondrial generation of reactive oxygen species, as they work harder to provide energy to muscles.

For cells, an increase in reactive oxygen species is both a signal to undertake beneficial activities, and a harm that must be defended against by antioxidants and repair of damaged molecules. The two are tied together. The outcome depends on the dose, a dose that rises steadily with age as damage and dysfunction overtakes the biological systems of the body.

Beneficial and Detrimental Effects of Reactive Oxygen Species on Lifespan: A Comprehensive Review of Comparative and Experimental Studies

Aging is the greatest risk factor for a multitude of diseases including cardiovascular disease, neurodegeneration, and cancer. Despite decades of research dedicated to understanding aging, the mechanisms underlying the aging process remain incompletely understood. The widely-accepted free radical theory of aging (FRTA) proposes that the accumulation of oxidative damage caused by reactive oxygen species (ROS) is one of the primary causes of aging.

To define the relationship between ROS and aging, there have been two main approaches: comparative studies that measure outcomes related to ROS across species with different lifespans, and experimental studies that modulate ROS levels within a single species using either a genetic or pharmacologic approach. Comparative studies have shown that levels of ROS and oxidative damage are inversely correlated with lifespan. While these studies in general support the FRTA, this type of experiment can only demonstrate correlation, not causation.

Experimental studies involving the manipulation of ROS levels in model organisms have generally shown that interventions that increase ROS tend to decrease lifespan, while interventions that decrease ROS tend to increase lifespan. However, there are also multiple examples in which the opposite is observed: increasing ROS levels results in extended longevity, and decreasing ROS levels results in shortened lifespan. While these studies contradict the predictions of the FRTA, these experiments have been performed in a very limited number of species, all of which have a relatively short lifespan.

Overall, the data suggest that the relationship between ROS and lifespan is complex, and that ROS can have both beneficial or detrimental effects on longevity depending on the species and conditions. Accordingly, the relationship between ROS and aging is difficult to generalize across the tree of life.

Comments

Thank you for sharing your thoughts on oxidation.
Antioxidants help.

Posted by: Richard Gnomebe at March 7th, 2021 6:00 AM

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