Atherosclerosis is probably one of the paradigms of disease linked to aging. Underlying the physiopathology of atherosclerosis are cellular senescence, oxidative stress, and inflammation. These factors are increased in the elderly and from chronic disease patients. Elevated levels of oxidative stress affect cellular function and metabolism, inducing senescence. This senescence modifies the cell phenotype into a senescent secretory phenotype. This phenotype activates immune cells, leading to chronic systemic inflammation. Moreover, due to their secretory phenotype, senescence cells present an increased release of highlighted extracellular vesicles that will change nearby/neighborhood cells and paracrine signaling. For this reason, searching for specific senescent cell biomarkers and therapies against the development/killing of senescent cells has become relevant. Recently, senomorphic and senolityc drugs have become relevant in slowing down or eliminating senescence cells. However, even though they have shown promising results in experimental studies, their clinical use is still yet to be determined.

Over the last hundred years, life expectancy in developed countries has increased because of healthier living habits and the treatment of chronic pathologies causing premature aging. Aging is an inexorable, time-dependent, multifactorial process characterized by a series of progressive and irreversible physiological changes associated with loss of functional, psychological, and social capabilities. Numerous factors, such as oxidative stress, inflammation, and cellular senescence, and an irreversible geriatric syndrome known as frailty, contribute to human body deterioration in aging. The speed of aging may differ between individuals depending on the presence or absence of multiple factors (genetic and/or environment) and the subsequent misbalance of homeostasis, together with the increase of frailty, which also plays a key role in developing chronic diseases. In addition, pathological circumstances have been reported to precipitate or accelerate the aging process. This review investigated the mechanisms involved in the developing pathologies, particularly chronic kidney disease, associated with aging.

Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD and the phenotype of microvesicles (MVs) subtypes, and cardiovascular events. The oxidative stress level of each participant was determined using an individualized OXY-SCORE. The relationship between pro-oxidant and antioxidant parameters and the expression of membrane markers in endothelial-derived microvesicles (EMVs) and platelet-derived microvesicles (PMVs) was established. Patients with advanced CKD (ACKD) and hemodialysis (HD) had a higher OXY-SCORE than healthy subjects (HS), whereas peritoneal dialysis (PD) patients had similar scores to HS. PD patients showed elevated PMVs and CD41 expression, whereas HD patients had higher EMVs and CD31 expression. Patients with ACKD had higher tissue factor (TF) expression in the PMVs and EMVs. TF expression was correlated with xanthine oxidase (XO) activity and was negatively correlated with antioxidant parameters. Patients with cardiovascular events show elevated TF. In conclusion, microvesicles and oxidative stress may serve as markers of cardiovascular risk in CKD, with TF expression in PMVs and EMVs being potential predictive and prognostic biomarkers of CVD.

Background/Objectives: Patients with chronic kidney disease (CKD) face higher risks of infections, poor vaccine responses, and cardiovascular diseases, leading to increased morbidity and mortality due to immune dysfunction and frailty. This study aims to evaluate immune status and frailty in CKD patients across different treatments, examine the influence of frailty on immune status, and link these factors to mortality. Methods: A total of 174 participants were included (end-stage renal disease, ESRD n = 40; hemodialysis, HD n = 40; peritoneal dialysis, n = 36; kidney transplant patients, n = 40; healthy subjects n = 18). Immunophenotyping of lymphocyte and monocyte subpopulations was performed, and frailty was assessed using the Edmonton Frail Scale. Principal component analysis (PCA) integrated immune and frailty variables to define an “immuno-fragile profile,” and survival was monitored for up to six years. Results: CKD patients, especially those on HD, showed decreased lymphocyte counts and proinflammatory monocyte subpopulations with increased expression of costimulatory molecules (B7.2/CD86 and ICAM-1/CD54). Frailty was most prevalent in HD patients (53%), with notable sex differences. PCA identified three components—lymphocyte counts, monocyte co-stimulatory expression, and frailty—that together explained 70% of the variance. Survival analysis revealed that patients with lower lymphocyte counts and higher frailty scores had increased mortality risk, especially in the HD and ESRD groups. Cox regression confirmed that the immuno-fragile profile independently predicted mortality. Conclusions: The integration of immune alterations and frailty defines an immuno-fragile profile strongly associated with mortality in CKD patients, which may serve as a robust prognostic tool to improve risk stratification and guide personalized interventions in clinical practice.