Telomere Length is a Biomarker of Cumulative Oxidative Stress, Biologic Age, and an Independent Predictor of Survival and Therapeutic Treatment Requirement Associated With Smoking Behavior

Abstract

Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10(16) radicals per cigarette (or 5 × 10(14) per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical population groups described in this study including elderly support the hypothesis that telomere length is a predictor of survival and therapeutic treatment requirement associated with smoking behavior.

Hormone-brain-aging relationships, broadly reactive with imidazole-containing dipeptides: targeting of telomere attrition as an aging biomarker and dynamic telomerase activity flirting

“…The results indicate that carnosine can reduce telomere shortening rate possibly by protecting telomere from damage [170]. Based on our own studies, we have suggested that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine and carcinine [9,10]. Cumulatively, in this article, we propose that patented specific oral formulations of nonhydrolyzed carnosine and carcinine provide a powerful tool for targeted inhibition of cumulative oxidative stress and inflammation associated with telomere shortening in age-related diseases and during smoking behavior ( Figure 8, Table 1) [9,10,15,132,135,143,171].…”

“…Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances WBC turnover [9,10,98,99]. Obese adults have shorter telomeres than their normal-weight counterparts, while this phenomenon is not present in childhood [98].…”

“…Biological activities of the nonhydrolyzed carnosine in the oral formulation are based on its antioxidant and antiglycating (transglycating) action that, in addition to heavy metal chelation and pH-buffering ability, makes carnosine an essential factor for preventing sight-threatening eye disorders having oxidative stress in their pathogenesis, neurodegeneration, and accumulation of senile features. The findings suggest that synergism is required between carnosine or other imidazole-containing compounds and reduced glutathione in tissues and cells for efficacious protection from protein carbonylation as a biomarker for the ability of the nontoxic compounds to reduce oxidative stress [9,10,15,132,135,143,171]. Potential therapeutic applications of oral forms of nonhydrolyzed carnosine and their specific mechanisms to manage telomere attrition and vascular aging might help elderly patients and smokers to withstand the pathogenetic problems of age-related disorders, metabolic and smoking-related diseases, accompanying with cumulative oxidative stress, accumulation of advanced glycation products, and accelerated biological aging linked with earlier onset of diseases [9,10,132,135,143,171].…”

“…Based on our own studies, we have suggested that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine and carcinine [9,10]. Cumulatively, in this article, we propose that patented specific oral formulations of nonhydrolyzed carnosine and carcinine provide a powerful tool for targeted inhibition of cumulative oxidative stress and inflammation associated with telomere shortening in age-related diseases and during smoking behavior ( Figure 8, Table 1) [9,10,15,132,135,143,171]. This product concept implements the potential role of the Oral product for safe therapeutic manipulation with molecular chaperones, telomeres, and telomerase biology; N-acetylcarnosine lubricant eye drops and oral product comprising carnosine, D-pantethine, or regulated/inducible molecular chaperone protein function (such as α-crystallin chaperone activity in the lens) offer potential novel therapies for reversal of (ripe) cataracts, retinal degeneration, and ocular complications of diabetes.…”

“…However, in this work, we raise a new therapeutic concept, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur, with the demonstrated evidence of telomere shortening appeared to be a hallmark of oxidative stress and disease [7][8][9][10].…”