A study suggests telomeres shortened by oxidative stress are correlated with aging, adding to a growing body of evidence.
Somu Yadav, PhD, and Pawan Kumar Maurya, PhD, both of the department of biochemistry at the University of Haryana in Mardendergarh, India conducted the study. Researchers explored the role oxidative stress plays in shortening structures called telomeres in hopes of making a definite connection.
What are telomeres?
Telomeres are protective end parts of chromosomes made of simple, short sequences of DNA. One of these DNA strands is rich in guanosine residue, according to the study authors. Telomeres cannot be replicated by normal DNA polymerase, and so they become shorter with cellular division, Yadav and Maurya said.1 Once cellular division occurs, overhanging single-strands of DNA appear to be damaged, and need protecting from DNA repair systems.1 Both age and age-related illness shorten telomeres.2,3 “Telomere length (TL) has increasingly been used as a biomarker of human aging because it has been shown to predict the chances of survival andlongevity,” Yadav and Maurya wrote.1
What is oxidative stress?
In a study published in 2017 in the journal Oxidative Medicine and Cellular Longevity, Gabriele Pizzino, PhD, of the department of clinical and experimental medicine at the University of Messina in Messina, Italy and colleagues defined oxidative stress. It is “a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products.”4 Oxidative stress is caused by a number of factors, including chronic inflammation, environmental factors such as ionizing radiations, pollutants, and heavy metals, and normal metabolic processes.1,4 Components of cells, such as nucleic acids, proteins, and lipids, then become oxidized due to ROS and free radicals, which alter the functioning of the cell.1 “The chronic accumulation of these ROS and damaged by-products cause oxidative stress,” Yadav and Maurya reported.1 Pizzino and colleagues emphasized that oxidative stress is “one of the major harms to individuals’ wellness and health.”4
To examine this connection between oxidative stress, shortened TL, and aging, Yadav and Maurya examined 105 healthy men and women between the ages of 20-77. They excluded smokers, pregnant and post-partum people, those with chronic or acute medical conditions such as asthma, diabetes, and tuberculosis, and those undergoing drug treatment from the study. Study participants each had 10ml of blood drawn through arm venipuncture after a 12-hour fast. Researchers noted The Institutional Human Ethics Committee of Central University of Haryana approved the study protocol.1
Researchers looked for signs of oxidative stress using a panel that included total antioxidant potential.TL level in leukocytes was examined. Samples underwent the Miller et al protocol desalting method for DNA extraction, the authors said.5 Multiplex real-time polymerase-chain reaction (PCR) was used to measure TL. Benzie and Strain method was used to measure ferric reducing ability of plasma (FRAP) values, while the Esterbauer and Cheeseman method was used to measure lipid peroxidation in terms of malondialdehyde (MDA). Erythrocyte glutathione (GSH) used the standard measuring method.
Indicators of a correlation
Yadav and Maurya said prior studies in cell cultures, mice, and people have already been completed.6 “However, there is no unequivocal evidence on the fact that the telomere shortening directly relates to the oxidative stress,” the authors noted.1 They said some studies report somatic redundancy as a biomarker of TL, while others support the correlation among TL, oxidative stress, and aging.7,8
For their study, Yadav and Maurya reported a statistically significant (p=0.001) decline in TL was observed that correlated by age. Researchers said this confirms another study performed by Richard M Cawthon, PhD, of the department of human genetics at the University of Utah in Salt Lake City and colleagues, which found a correlation between shortened TL in blood samples and mortality in age-related diseases.9 That study examined 143 individuals over 60 years of age, and found that shortened TL in blood DNA samples had poorer survival rates, which was associated with “a 3.18-fold higher mortality rate from heart disease (95% CI 1·36–7·45, p=0·0079), and an 8·54-fold higher mortality rate from infectious disease (1·52–47·9, p=0·015).”9
Yadav and Maurya said that in their study, TL had a positive correlation with the FRAP value (r=0.8811) and reduced GSH (r=0.8209). Conversely, TL was negatively correlated with MDA (r=-0.7191).1 Yadav and Maurya confirmed that these results support a correlation between the length of the telomere and aging and adds to a growing body of evidence supporting the link among TL, oxidative stress, and aging.
The study authors reported several study limitations. First, they said different blood samples could have distinct leukocyte-subtype proportions that could affect the results of the study.1 Second, Yadav and Maurya said average TL was used to calculate the relative ratio of ng telomeres to ng of albumin (T/S ratio), which the authors said cannot be reported as a direct measure of the region of the telomere.1 They added that “oxidative stress levels could have fluctuated over time during blood collection.” Telomerase activity was not measured, and that this “could have impacted current findings because telomerase affects the rate of TL change in peripheral blood mononuclear cells,” the authors said.1
Although the data does show a correlative link between telomere damage and oxidative stress, Yadav and Maurya emphasized that more in vivo studies are necessary to fully understand what role oxidative stress plays in the human aging process. “Prospective and experimental studies are essential to establish a causal relationship between TL and oxidative stress markers and also the possible mechanisms involved,” Yadav and Maurya wrote.1 They said that based on the research findings, antioxidative therapies may be useful in treatments to prevent telomere shortening.1
“In view of tremendous scope for these novel findings in medical and diagnostics and therapeutics, we believe that these findings will aid oxidative stress studies in human aging,” the authors concluded.1