In 1954, the possibility of a nuclear war was on the horizon. The public recognized that increased exposure to radiation was threatening to longevity and that antioxidants could be used to neutralize its effects. Sources of longevity were of importance around this time, as America pushed to increase its average life expectancy (Harman, 2009, p. 774). Along with many others, Denham Harman was interested in what he describes as “the long-expressed desire of ‘man’ to ‘live long but not be old’” (Harman, 2009, p. 774). His work endeavors attempted to reveal that free radicals were the explanation hidden behind aging. He proposed that the mortal effects of radiation exposure mirrored that of free radical oxidation within the body. His theory was discarded by scholars around the world for years to come. Despite criticism, Harman continued to pursue funding to research his theory through the eighties (Harman, 2009, p. 777-781). For the last sixty years, free radicals and oxidative stress have been a topic of discussion among scientists all over the world. Although it is much better understood now than it was in the 1950s, debate still remains about whether the free radical theory of aging is valid. However, a great deal of research shows its potential to understand the causes of aging and provides a promising outlook on increasing life expectancy, making it a focal point of the biological theory of aging.
Chemical bonds are formed between elements that constitute a compound by the sharing or transferring of electrons. Compounds typically follow the octet rule, in which each of its respective elements has eight valence electrons. It is important for atoms and compounds to follow the octet rule, because when they do not, they become unstable (Loudon & Parise, 2016, p. 3-9). Free radicals are unstable species that aggressively try to fill their valence shell and consequently damage biomolecules in the human body. Antioxidants counter the damage that free radicals cause in the body, by providing free radicals with a source from which they can take an electron. However, the balance between free radicals and antioxidants is delicate, and when thrown off causes oxidative stress, which is related to aging (Afanas’ev, 2010, p. 84). In summary, Harman theorized that free radicals accumulate as we age and cause oxidative damage, which lead to disease.
This theory was later expanded to differentiate free radicals, noting that not all of them were necessarily life-threatening. Despite the advancements, one free radical in particular remained the main source of concern: reactive oxygen species, or ROS. ROS is vital to humans in that it plays an important role in cell signaling. However, in excess, it leads to oxidative stress. This is important for gerontology because there is a positive correlation between age and ROS production and a negative correlation between age and balancing free radicals and antioxidants (Afanas’ev, 2010, p. 75-76).
Today, a major source of debate within the theory is whether the source of ROS is really mitochondria, as assumed by Harman, or if it is NOX. A respiratory burst occurs when cells use oxygen by activating NOX. NOX are enzymes used throughout the body that generate ROS. Proponents of NOX being the primary source of ROS claim that its science is broadly unexplored, and therefor undervalued. In the near future, this debate may be a source of weakness for the free radical theory of aging if proponents can confirm that in fact NOX is missing from the free radical oxidation equation (Krause, 2007, p. 256-261).
There are a couple theories that oppose the free radical theory of aging altogether. TOR theory suggests that another aging pathway promotes aging faster than ROS, making that the primary source of aging. This TOR pathway governs cell growth and function, and when overworked, aging emanates. However, it is important to note that the science behind this theory is not concrete, and that the TOR pathway is most likely regulated by ROS (Afanas’ev, 2010, p. 84).
Harman’s free radical theory had implications beyond gerontology. His work also helped disclose basic knowledge on free radicals that was once unknown to biologists and chemists alike. Today, this theory continues to develop, and influences preventative practices taken to increase longevity. The ramifications that this theory has offered to science and the human life make it particularly noteworthy.