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Aging theories point to negative effects of oxidative stress

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The theory of free radical aging hypothesizes oxidative stress causes degenerative diseases, while the free radical frailty theory suggests free radicals cause frailty, rather than age-related diseases.

The concept of aging has intrigued scientists for over a century, and philosophers for thousands of years.1 The primary interest usually revolves around the decline in memory, or cognitive function, as age progresses. Due to higher worldwide life expectancy, this area of research has become increasingly important. This is, therefore, an ideal starting point when discussing healthy aging, and in line with the World Health Organization (WHO) definition of healthy aging, where four of the five parameters are associated with cognitive functions.

Studies on aging in the 1920s were conducted by psychologists, where gradual age-related memory slippage was observed.2 Various theoretical models of aging and memory decline were proposed, until, in 1956, the investigation of aging moved from psychology to physiology, with Denham Harman’s introduction of the “theory of free radical aging.”

The theory states aging, and all degenerative diseases associated with aging are directly attributable to damaging attacks from free radicals (i.e., reactive oxygen species [ROS] on cells and tissues).2 For roughly 50 years, this theory was the central dogma for physiological examinations into the mechanisms of aging. Despite the fact that, in recent years, new theories have emerged that expand upon this theory,3 draw into question its future usefulness,4 or shift the focus from “free radical aging” to “free radical frailty,”5,6 it remains one of the central research topics regarding the concept of healthy aging.7

The transition to the “free radical frailty” theory by Jose Viña and co-workers at the Freshage Research Group in 2018 harmonized data discrepancies that were irreconcilable with “free radical aging,” and effectively separated life expectancy and quality of life.5 The authors hypothesized ROS do not necessarily directly dictate life expectancy, but rather, with increased oxidative stress due to the presence of excessive free radicals, the quality of life is diminished through frailty and eventually disability.

Regardless which theory is used to decipher the physiology of aging, the clear consensus is aging causes: 1) an increase in the rate of generation of ROS; 2) a decline in the natural antioxidant defenses and 3) a decline in the repair efficiency of molecules that have been damaged by ROS. Combined, these facts mean that as we age, ROS increases production and tissues have a higher susceptibility to experience oxidative damage.7 This oxidative damage to tissues is particularly damaging within the brain, due to the non-mitotic nature of neurons.8 Numerous publications have illustrated a causal relationship between neurodegenerative disorders, such as Alzheimer’s disease, and oxidative stress exists, which was the focus of a recent review by Collin.9

Learn more about different theories of aging and ingredients that help reduce oxidative stress in this full article, which appears in INSIDER’s Healthy Aging digital magazine.

Haraldur Gardarsson, Ph.D., is the quality control manager at Algalif. He has a doctorate degree in Chemistry from ETH Zurich in Switzerland. He has held numerous academic positions throughout his career, most recently as an adjunct lecturer at the University of Iceland. He joined the Algalif team in 2015.


1. Park D, Festini S. “Theories of Memory and Aging: A Look at the Past and a Glimpse of the Future.” J Gerontol B Psychol Sci Soc Sci. 2017 Jan;72(1):82-90.

2. Harman D. “Aging: a theory based on free radical and radiation chemistry.” J Gerontol. 1956 Jul;11(3):298-300.

3. Kirkwood T, Kowald A. “The free-radical theory of ageing--older, wiser and still alive: modelling positional effects of the primary targets of ROS reveals new support.” Bioessays. 2012 Aug;34(8):692-700. DOI: 10.1002/bies.201200014.

4. Gladyshev V. “The free radical theory of aging is dead. Long live the damage theory!” Antioxid Redox Signal. 2014 Feb 1;20(4):727-31. DOI: 10.1089/ars.2013.5228.

5. Viña J, Borras C, Gomez-Cabrera M. “A free radical theory of frailty.” Free Radic Biol Med. 2018 Aug 20; 124:358-363. DOI: 10.1016/j.freeradbiomed.2018.06.028.

6. Viña J. “The free radical theory of frailty: Mechanisms and opportunities for interventions to promote successful aging.” Free Radic Biol Med. 2019 Feb 5. pii: S0891-5849(18)32651-0. DOI: 10.1016/j.freeradbiomed.2019.01.045.

7. Sohal R, Weindruch R. “Oxidative stress, caloric restriction, and aging.” Science. 1996 Jul 5;273(5271):59-63.

8. Nowakowski R. “Stable neuron numbers from cradle to grave.” Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12219-20.

9. Cheignon C et al. “Oxidative stress and the amyloid beta peptide in Alzheimer's disease.” Redox Biol. 2018 Apr; 14:450-464. DOI: 10.1016/j.redox.2017.10.014.

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