Keywords: Aging, Reactive Oxygen Species, Apoptosis

Aging is a biological reality and has its own dynamics, which is beyond human control. Aging is the accumulation process of diverse detrimental changes in cells and tissues with advancing age which result in an increase in the risks of diseases and death. Aerobic cells produce reactive oxygen species (ROS) as a byproduct of their metabolic processes. ROS cause oxidative damage to macromolecules under conditions when the antioxidant defense of body is overwhelmed with ROS (Harman, 2006). A certain amount of oxidative damage takes place even under normal conditions, however, the rate of damage increase with aging process because of a decrease in efficiency of antioxidative and repair mechanisms (Figure 1).

 

Aging
Figure 1: Role of reactive oxygen species (ROS) in the process of aging

 

For the year 2050, the predicted world population will be 9.3 billion (Population Reference Bureau, Washington, 2004). India will be the most populous nation by 2050 with a population of 1.63 billion followed by China, US, Indonesia, and Nigeria. By 2050, Asia will become the home for almost two-thirds of the world’s population of people with the age over 60 years. The increasing number of older people in Indian society has been well perceived from census data. The population over the age of sixty years has nearly tripled in last 50 years and the relentless increase continues in projected population figures by demographic experts.

Reactive Oxygen Species (ROS) – causative agent of aging

There are more than three hundred theories, which attempt to explain the process of aging. The Free radical theory offers the best mechanistic elucidation of the aging process and other age-related phenomenon proposed by Harman in 1956. Free radical exists with one or more unpaired electron in an atomic or molecular orbital. Free radicals are generally unstable, highly reactive, and energized molecules. Reactive oxygen species are chemically-reactive molecules containing oxygen. Reactive oxygen species can be classified into oxygen-cantered radicals and oxygen-centered non radicals. Oxygen-centered radicals are superoxide anion (·O2), hydroxyl radical (·OH), alkoxyl radical (RO·), and peroxyl radical (ROO·). Oxygen-centered non radicals are hydrogen peroxide (H2O2) and singlet oxygen (1O2). Other reactive species are nitrogen species such as nitric oxide (NO·), nitric dioxide (NOO·), and peroxynitrite (OONO) (Maurya et al., 2015).

Reactive oxygen species or free radicals in biological systems can be formed by prooxidative enzyme systems, lipid oxidation, irradiation, inflammation, smoking, air pollutants, and glycoxidation. Clinical studies reported that reactive oxygen species are associated with many age-related degenerative diseases, including atherosclerosis, vasospasms, cancers, trauma, stroke, asthma, hyperoxia, arthritis, heart attack, age pigments, dermatitis, cataractogenesis, retinal damage, hepatitis, liver injury, and periodontics (Maurya et al., 2016). Benign functions of free radicals have been reported, including activation of nuclear transcription factors, gene expression, and a defence mechanism to target tumor cells and microbial infections.

Free radicals (oxidants) come from two major sources: a) endogenous, and b) exogenous. Endogenous free radicals are produced in the body by four different mechanisms.

  • From the normal metabolism of oxygen-requiring nutrients. Mitochondria- the intracellular powerhouses which produce universal energy molecule, adenosine triphosphate (ATP)-normally consumes oxygen in this process and convert it to water. However, unwanted by-products- such as superoxide anion, hydrogen peroxide and hydroxyl radical- are inevitably produced, due to incomplete reduction of the oxygen molecule. It has been estimated that > 20 billion molecules of oxidants per day are produced by each cell during normal metabolism. Imagine what happens with inefficient cell metabolism.
  • White blood cells destroy parasites, bacteria, and viruses by using oxidants such as nitric oxide, superoxide, and hydrogen peroxide. Consequently, chronic infections result in prolonged phagocytic activity and increased exposure of body tissues to oxidants.

(3) Other cellular components called peroxisomes produce hydrogen peroxide as a byproduct of degradation of fatty acids and other molecules. In contrast to mitochondria which oxidize fatty acids to produce ATP and water, peroxisomes oxidize fatty acids to produce heat and hydrogen peroxide. The peroxide is then degraded by catalase. Under certain conditions, some of the hydrogen peroxide escapes to wreak havoc into other compartments in the cell.

  • An enzyme in the cells called cytochrome P450 is one of the body’s primary defenses against toxic chemicals ingested along with food. However, the induction of these enzymes prevents damage caused by toxic foreign chemicals like drugs, pesticides results in the production of oxidant by-products.

Exogenous factors such as UV exposure, herbicides, xenobiotics and air pollutants also cause the generation of ROS.

How to slow down the clock of aging?

Very low percentage of Indian population is aware of effects of antioxidants found in fruits and vegetables, therefore there is a great opportunity either to improve health or to slow down the aging process by increasing consumption of fruits and vegetables in the regular diet. Recent studies have shown that consumption of many plant products with antioxidant activity is helpful in delaying aging and age-associated diseases (Kumar et al., 2016). Polyphenols in food plants are a versatile group of phytochemicals with antioxidant activity. Epidemiological studies showed that increased consumption of phenolic compounds reduced the risk of cardiovascular disease, certain types of cancers and even aging (Maurya and Prakash, 2011). Flavonoids are a group of polyphenolic compounds which are present in fruits, vegetables, and certain beverages and have diverse beneficial biochemical and antioxidant effects. The protective role of flavonoids involves several mechanisms of action: direct antioxidant effect, inhibition of enzymes of oxygen-reduction pathways and sequestration of transient metal cations.

The normal human body has a very complex and efficient antioxidant system consisting of a number of interrelated antioxidant compounds and enzymes. The mechanism(s) that are thought to be involved in increased oxidative stress as a function of human age include not only oxygen free radicals generation but also change in the tissue/plasma content and the activity of antioxidant defense system. Studies indicate that a high intake of dietary flavonoids by higher age groups may provide some protection against the development of age-related diseases and slow down the aging process. 

Future plans

Pathological events such as oxidative stress, due to the elevated release of free radicals and reactive oxygen or nitrogen species, and subsequently enhanced oxidative modification of lipids, protein, nucleic acids, as well as modulation of apoptotic signaling pathways contribute towards aging. The identification of protective food components is one strategy to facilitate healthy aging. Flavonoids were shown to activate key enzymes in mitochondrial respiration and to protect cells by acting as antioxidants, thus breaking the vicious cycle of oxidative stress and tissue damage. Recent data indicate the protective effect of flavonoids on various age-related diseases. Whereas most of these effects have been shown invitro, limited data for invivo effects are available. Nevertheless, several reports support the concept that flavonoid intake inhibits certain biochemical processes of aging. The information gained from these studies can be utilized to determine the role of dietary flavonoids as anti-aging compounds and these compounds may have potential be used in anti-aging therapy.

References:

  1. Harman D. Free radical theory of aging: an update: increasing the functional life span. Ann N Y Acad Sci. 2006;1067:10-21.
  2. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298-300.
  3. Maurya PK, Kumar P, Chandra P. Biomarkers of oxidative stress in erythrocytes as a function of human age. World J Methodol. 2015;5(4):216-22.
  4. Maurya PK, Noto C, Rizzo LB, Rios AC, Nunes SO, Barbosa DS, Sethi S, Zeni M, Mansur RB, Maes M, Brietzke E. The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2016 ;65:134-44.
  5. Kumar P, Chand S, Maurya PK. Quercetin-modulated erythrocyte membrane sodium-hydrogen exchanger during human aging: correlation with ATPase’s. Arch Physiol Biochem. 2016;122(3):141-7.
  6. Maurya PK, Prakash S. Intracellular uptake of (-)epicatechin by human erythrocytes as a function of human age. Phytother Res. 2011;25(6):944-6.

Authored By:

Dr. Pawan Kumar Maurya

Assistant Professor
Amity Institute of Biotechnology
Amity University
Noida – 201303, U.P. India