Sarcopenia and malnutrition are commonly occurring conditions in the elderly that frequently coexist, leading to substantial effects on morbidity/mortality. Evidence established muscle-specific microRNAs (miRNAs) or myomiRs as essential regulators of skeletal muscle processes, from myogenesis to muscle homeostasis. This study aimed to evaluate the association between myomiRs and sarcopenia and explore the potential of nutrition in mediating this association. qPCR was employed to characterize the myomiR-1, -133a/b, -206, -208b, and -499 expression profiles of 109 non-sarcopenic and 109 sarcopenic subjects. In our sample, the proportion malnourished or at-risk subjects was higher in sarcopenia (p < 0.001). Among the detected myomiRs (miR-133a/b and miR-206), lower levels of miR-133b was significantly associated with the presence of sarcopenia (p = 0.006); however, this relationship was not independent from nutritional status in multivariate analysis, suggesting a mediating effect of nutrition on the relationship between miR-133b and sarcopenia. Correlation analyses showed that lower miR-133b levels were associated with poor nutritional status (Mini Nutritional Assessment Long Form (MNA-LF) score, p = 0.005); furthermore, correlations with albumin, ferritin, and iron were found. Similar results were obtained for miR-206. Statistically more significant correlations were observed in subjects with sarcopenia. In conclusion, our findings highlight a nutrient-miR-133b/miR-206 pathway having a potential role in the age-related muscle decline.

Xenobiotic-metabolizing enzymes (XME) mediate the body’s response to potentially harmful compounds of exogenous/endogenous origin to which individuals are exposed during their lifetime. Aging adversely affects such responses, making the elderly more susceptible to toxics. Of note, XME genetic variability was found to impact the ability to cope with xenobiotics and, consequently, disease predisposition. We hypothesized that the variability of these genes influencing the interaction with the exposome could affect the individual chance of becoming long-lived. We tested this hypothesis by screening a cohort of 1112 individuals aged 20–108 years for 35 variants in 23 XME genes. Four variants in different genes (CYP2B6/rs3745274-G/T, CYP3A5/rs776746-G/A, COMT/rs4680-G/A and ABCC2/rs2273697-G/A) differently impacted the longevity phenotype. In particular, the highest impact was observed in the age group 65–89 years, known to have the highest incidence of age-related diseases. In fact, genetic variability of these genes we found to account for 7.7% of the chance to survive beyond the age of 89 years. Results presented herein confirm that XME genes, by mediating the dynamic and the complex gene–environment interactions, can affect the possibility to reach advanced ages, pointing to them as novel genes for future studies on genetic determinants for age-related traits.

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are markers of premature cellular senescence. This may contribute to age-related diseases, including Alzheimer’s disease (AD), and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case–control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, who were all from Calabria, a southern Italian region. Following regression analysis, telomeres were found significantly shorter in LOAD cases than in controls (48% and 41% decrease for sporadic and familial cases, respectively; p < 0.001 for both). Interestingly, LTL was associated with disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, and the presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the pathogenesis of LOAD.

Advanced age is the largest risk factor for late‐onset Alzheimer's disease (LOAD), a disease in which susceptibility correlates to almost all hallmarks of aging. Shared genetic signatures between LOAD and longevity were frequently hypothesized, likely characterized by distinctive epistatic and pleiotropic interactions. Here, we applied a multidimensional reduction approach to detect gene–gene interactions affecting LOAD in a large dataset of genomic variants harbored by genes in the insulin/IGF1 signaling, DNA repair, and oxidative stress pathways, previously investigated in human longevity. The dataset was generated from a collection of publicly available Genome Wide Association Studies, comprising a total of 2,469 gene variants genotyped in 20,766 subjects of Northwestern European ancestry (11,038 LOAD cases and 9,728 controls). The stratified analysis according to APOE*4 status and sex corroborated evidence that pathways leading to longevity also contribute to LOAD. Among the significantly interacting genes, PTPN1, TXNRD1, and IGF1R were already found enriched in gene–gene interactions affecting survival to old age. Furthermore, interacting variants associated with LOAD in a sex‐ and APOE‐specific way. Indeed, while in APOE*4 female carriers we found several inter‐pathway interactions, no significant epistasis was found in APOE*4 negative females; conversely, in males, significant intra‐ and inter‐pathways epistasis emerged according to APOE*4 status. These findings suggest that interactions of risk factors may drive different trajectories of cognitive aging. Beyond helping to disentangle the genetic architecture of LOAD, such knowledge may improve precision in predicting the risk of dementia and enable effective sex‐ and APOE‐stratified preventive and therapeutic interventions for LOAD.

The past years have seen an increasing concern about frailty, owing to the growing number of elderly people and the major impact of this syndrome on health and social care. The identification of frail people passes through the use of different tests and biomarkers, whose concerted analysis helps to stratify the populations of patients according to their risk profile. However, their efficiency in prognosis and their capability to reflect the multisystemic impairment of frailty is discussed. Recent works propose the use of miRNAs as biological hallmarks of physiological impairment in different organismal districts. Changes in miRNAs expression have been described in biological processes associated with phenotypic outcomes of frailty, opening intriguing possibilities for their use as biomarkers of fragility. Here, with the aim of finding reliable biomarkers of frailty, while considering its complex nature, we revised the current literature on the field, for uncovering miRNAs shared across physical and cognitive frailty domains. By applying in silico analyses, we retrieved the top-ranked shared miRNAs and their targets, finally prioritizing the most significant ones. From this analysis, ten miRNAs emerged which converge into two main biological processes: inflammation and energy homeostasis. Such markers, if validated, may offer promising capabilities for early diagnosis of frailty in the elderly population.