Andrea Di Nisio

Background/Objectives: Male infertility is multifactorial, involving genetic, environmental, lifestyle, and medical factors. Recent research has underscored the influence of lifestyle choices, such as dietary habits, smoking, alcohol abuse, and metabolic disturbances, on sperm quality. In this context, nutrition plays a pivotal role: adherence to a healthy diet like the Mediterranean Diet (MD), which emphasizes seasonal, fresh, and whole foods, has been linked to improved sperm performance. Conversely, a high intake of ultra-processed foods (UPFs), characterized by additives, high levels of sugars, fats, and salt, and a nutrient-poor profile, may impair sperm quality. Methods: Based on data supporting the reproductive health benefits of the MD, this observational cross-sectional study aimed at evaluating the possible relationship between MD adherence, assessed using the 14-point a priori Mediterranean Diet Adherence Screener (MEDAS) and intake of ultra-processed foods (UPFs), based on the NOVA classification, and sperm quality in 358 individuals (mean age 34.6 ± 9.3 years) who spontaneously referred to our center of reproductive medicine. Semen analyses were performed according to the WHO 2021 criteria. Hormonal profiles (FSH, LH, testosterone, SHBG, bioavailable testosterone, and calculated free testosterone) were also determined. Results: MD adherence score was significantly and positively correlated with semen parameters, whilst negatively correlated with FSH and LH levels. In contrast, UPF intake was correlated with poor semen parameters, whilst no association was observed with hormonal levels. Multivariate analyses confirmed these associations and showed the independency from age and BMI. Notably, among men with FSH levels < 8 IU/mL, higher quartiles of UPF intake had lower markers of sperm quality, particularly for viability and typical morphology. Differently, high MD adherence scores were associated with high quality sperm parameters even when FSH levels were >8 IU/mL. Conclusions: This study provides evidence that the adherence to MD, and conversely reduced intake of ultra-processed foods, is associates with a better semen profile. These findings suggest the possible role of dietary interventions as a modifiable factor in the management of male infertility.

Telomeres protect chromosome ends from damage, but they shorten with each cell division due to the limitations of DNA replication and are further affected by oxidative stress. This shortening is a key feature of aging, and telomerase, an enzyme that extends telomeres, helps mitigate this process. Aging is also associated with mitochondrial dysfunction, leading to increased reactive oxygen species (ROS) that exacerbate cellular damage and promote apoptosis. Elevated ROS levels can damage telomeres by oxidizing guanine and disrupting their regulation. Conversely, telomere damage impacts mitochondrial function, and activation of telomerase has been shown to reverse this decline. A critical link between telomere shortening and mitochondrial dysfunction is the DNA damage response, which activates the tumor suppressor protein p53, resulting in reduced mitochondrial biogenesis and metabolic disruptions. This highlights the bidirectional relationship between telomere maintenance and mitochondrial function. This review explores the complex interactions between telomeres and mitochondria across various cell types, from fibroblasts to sperm cells, shedding light on the interconnected mechanisms underlying aging and cellular function.