The free-radical theory of aging, first proposed by Denham Harman in the 1950s, suggests that the accumulation of damage caused by free radicals—particularly reactive oxygen species (ROS)—over time is a primary driver of the aging process and related degenerative diseases.
This theory has been foundational in understanding how oxidative stress impacts cellular aging and has evolved with new insights into the complexities of biology and aging
Here’s a detailed look at the key aspects of this theory:
Core Concepts of the Free-Radical Theory of Aging
1. Production of Free Radicals:
Free radicals are reactive molecules with unpaired electrons, making them highly reactive. In biological systems, the primary sources of free radicals are metabolic processes, especially in the mitochondria where oxygen is used to produce energy (ATP).
Other sources include exposure to environmental toxins, UV radiation, and inflammatory processes.
2. Oxidative Damage:
Over time, ROS can damage vital cellular components such as DNA, proteins, and lipids. This damage can lead to mutations, malfunctioning proteins, and lipid peroxidation, disrupting cell structure and function.
This cumulative damage is believed to contribute to the decline in physiological function observed with aging.
3. Mitochondrial Dysfunction:
Mitochondria are both a major source and a primary target of ROS. As mitochondria sustain damage from ROS, their efficiency in energy production declines, leading to increased ROS production and further damage in a vicious cycle.
This mitochondrial dysfunction is a key aspect of aging and is associated with a decline in cellular energy levels and increased cellular senescence.
4. Cellular Senescence:
Accumulation of oxidative damage can lead to cellular senescence, a state in which cells no longer divide but remain metabolically active and often secrete inflammatory factors.
Senescent cells accumulate with age and contribute to aging and the development of age-related diseases by disrupting tissue function and promoting inflammation.