Studying models of healthy aging and exceptional longevity is crucial to understanding a possible longevity signature, as most show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyzes the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19–111 years, aiming to understand the immune-inflammatory (IMFLAM) role in achieving longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical differences were found when comparing the values of semi- and supercentenarians to other age groups, which are similar to adults and lower than younger centenarians. Regarding ARIP values, it is noteworthy that when comparing the CD8⁺ Naïve/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

Background: Assessing nutrition-related health risks in older individuals is often overlooked in clinical practice due to the lack of appropriate methods of evaluation. While anthropometric measurements and body composition analyses are mainly used, these tools are not standardized for the oldest old and fail to account for age-related changes. This underscores the need for improved assessment techniques that accurately capture the progressive and non-linear shifts in nutritional status throughout the aging process. Accordingly, the primary aim of our paper is to identify the most effective tools to use for evaluating nutritional status in the oldest population. Methods: To address this gap, we conducted a cross-sectional study, investigating the nutritional status of a cohort of Sicilian individuals aged between 65 and 111, using methods commonly applied to adult and older adult populations. These included the BIoimpedance Analysis (BIA), the Mini Nutritional Assessment (MNA) evaluation, and nutritional risk indices such as the COntrolling NUTritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI). Results: Despite the oldest population being classified as “at risk” of malnutrition by the MNA or “cachetic” by BIA, our results indicated a “normal” or “low risk” of malnutrition when assessments were performed using tools (GNRI and CONUT) that were not reliant on body composition parameters. These findings align with clinical history assessments conducted during their recruitment. Conclusions: This pilot study highlights the need for future research aimed at developing standardized, multidimensional assessment models tailored to the heterogeneity of each age group, to improve risk stratification, clinical outcomes, and personalized nutritional care.

Studying models of healthy aging and exceptional longevity is crucial to understand a possible longevity signature as most of them show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish Flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyse the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, trying to understand the immune-inflammatory (IMFLAM) role to achieve longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical difference is observed when analysing the values for semi- and supercentenarians with those for other age groups, whose values are similar to that of adults and less than younger centenariansRegarding ARIP values, it is noteworthy that when comparing the CD8 Naive/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

Background/Objectives: The increasing use of electronic devices is reshaping lifestyle by offering new avenues for health behavior change. These tools provide to monitor health, fitness, and nutrition, promoting healthier lifestyles to prevent non-communicable diseases (NCDs). This umbrella review (conducted according to PRISMA 2020 guidelines, registered on PROSPERO CRD42024511141) assesses the effectiveness of wearable devices and mobile applications in improving healthy lifestyle behaviors to mitigate the risk of NCDs. Methods: Systematic reviews and meta-analyses (n = 27) focusing on digital tools for health behavior change were analyzed, with emphasis on their integration into daily life and their impact on health outcomes, including body weight, metabolic and anthropometric parameters, and dietary quality. Results and Conclusions: Interventions leveraging gamification, social interaction, and goal-setting (6/27) have shown greater efficacy in improving body-nutrition profile. The integration of eHealth technologies holds transformative potential for preventive healthcare and positive biology. These tools can contribute to healthier lifestyles, extended life expectancy, and reduced healthcare costs, although current limitations exist, including data accuracy, privacy concerns, and sustaining user engagement over time.

Autoimmune diseases (ADs) comprise a heterogeneous group of disorders characterised by a breakdown of immune tolerance and chronic immune-mediated tissue damage. Their onset and progression result from a complex interplay between genetic susceptibility, hormonal influences, immune regulatory mechanisms, and environmental exposures collectively referred to as the exposome. A striking feature of ADs is their pronounced sexual dimorphism, with a markedly higher prevalence in women for most conditions, alongside sex-specific differences in clinical presentation, severity, and prognosis. This review provides a comprehensive overview of the genetic and environmental determinants contributing to autoimmunity, with particular emphasis on how sex- and gender-related factors shape immune tolerance and disease susceptibility. We discuss central and peripheral tolerance mechanisms, the role of key regulators such as AIRE and FOXP3, sex chromosome-linked effects including X-chromosome inactivation, and the immunomodulatory impact of sex hormones across different life stages. Furthermore, we examine how environmental exposures, infections, and geographic variability interact with genetic background and sex-specific immune regulation to influence autoimmune disease risk. By integrating biological sex and gender-related factors within the framework of immune tolerance and the exposome, this review highlights the need for a sex-aware and personalised approach to understanding, diagnosing, and treating ADs.

Centenarians, semi-supercentenarians and supercentenarians (i.e. oldest centenarians) display complex and heterogeneous immune remodelling. In this setting, immune at-trition, memory, cytotoxic defence, inflammatory regulation and tissue surveillance remain sufficiently balanced to support survival with relatively preserved health. This review examines these processes within an integrated framework encompassing sex and gender differences, genetic background, the exposome and immunobiography. We consider how haematopoietic stem cell ageing, age-related myeloid bias, thymic invo-lution, immune ageing and inflammaging contribute to immune-system remodelling across the life course. We then review evidence on immunity in centenarians and in semi- and supercentenarians, including NK cell expansion, T and B cell remodelling and the persistence of long-term immunological memory, as characterised by conventional flow cytometry and, more recently, single-cell transcriptomic analyses. Available data suggest that exceptional longevity does not reflect the maintenance of a youthful immune system, but rather the capacity to accommodate and compensate for age-related immune re-modelling through preserved cytotoxic surveillance, controlled inflammation, main-tained immune memory and favourable lifelong adaptation to antigenic exposures. Understanding these mechanisms may help identify immune trajectories associated with healthspan, delayed morbidity and resistance to age-related diseases.