A research team based at the Institute of Genetic Epidemiology, Medical University of Innsbruck, Austria, have shown that the relative telomere length (RTL) is associated with age-related macular degeneration (AMD) in women, but not in men (odds ratio 1.14 in women, vs 1.01 in men). The study, reported in the journal Investigative Ophthalmology & Visual Science(IOVS, 2022;63(5):30), found that there was an association between shorter RTL and AMD, independent from potential risk factors. The results appear to be in line with a limited “sex-differential pathway from oxidative stress to AMD” however, there has been sparse evidence in the literature to from a broader association and therefore large epidemiological studies with detailed ophthalmologic characterizations are needed.
The current study measured RTL in participants using a multiplex quantitative PCR based assay using a cohort of 2,262 individuals ranging from 70 to 95 years old. In the age- and sex-adjusted logistic regression analyses, results of the study observed an 8% higher odds for AMD, per 0.1 unit shorter RTL (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.02–1.14; P = 0.005). In addition, the estimates remained stable when adjusted for smoking, high-density lipoprotein cholesterol, cardiovascular disease, diabetes, and hypertension. As highlighted, the association was only present in women (OR = 1.14; 95% CI, 1.06–1.23; P < 0.001), but not in men (OR = 1.01; 95% CI, 0.93–1.10; P = 0.76). Commenting on the observation, the journal reported that the “results show an association of RTL with AMD that was restricted to women. This is in line with altered reactive oxygen species levels and higher telomerase activity in women and provides an indication for a sex-differential pathway for oxidative stress and AMD”.
As well-known in the literature, and as identified in the current report, telomeres are non-coding repetitive sequences with a particular sequence motif at the ends of linear chromosomes. These sequences range from 5- to 15kb nucleotides and these are critical for genomic integrity, allowing to cap and protect the genetic material. Through-out life, telomeres shorten progressively and, as age increases with each cell replication, DNA polymerase is unable to completely replicate the 3’ end of the lagging DNA strand. In their report, the authors proposed a biological hypothesis indicating oxidative stress associated with inflammation with the relevant telomere structure which contains a “high amount of the nucleotide guanine, which is more likely to be oxidized than other DNA bases”. In addition, several AMD risk genes in the literature are known to encode for proteins associated with oxidative stress. Commenting in their paper, “it is hypothesized that telomere attrition is induced when the energy household of a cell is unbalanced and the anabolic metabolism has to be reduced via the target of rapamycin”.