A cell's function is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here, we combine single-cell and spatial transcriptomic data to discover cellular niches within eight regions of the human heart. We map cells to micro-anatomic locations and integrate knowledge-based and unsupervised structural annotations. For the first time, we profile the cells of the human cardiac conduction system, revealing their distinctive repertoire of ion channels, G-protein coupled receptors, and cell interactions using a custom CellPhoneDB.org module. We show that the sinoatrial node is compartmentalised, with a core of pacemaker cells, fibroblasts and glial cells supporting paracrine glutamatergic signalling. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions, providing unexpected mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG+ and IgA+ plasma cells forming immune niches which may contribute to infection defence. We define a ventricular myocardial-stress niche enriched for activated fibroblasts and stressed cardiomyocytes, cell states that are expanded in cardiomyopathies. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be deployed to other tissues and organs.

Aim The main purpose of the present study was to verify the feasibility of wearable inertial sensors (IMUs) in a clinical setting to screen gait and functional mobility in Italian older persons. In particular, we intended to verify the capability of IMUs to discriminate individuals with and without cognitive impairments and assess the existence of significant correlations between mobility parameters extracted by processing trunk accelerations and cognitive status. Methods This is a cross-sectional study performed on 213 adults aged over 65 years (mean age 77.0 ± 5.4; 62% female) who underwent cognitive assessment (through Addenbrooke’s Cognitive Examination Revised, ACE-R) instrumental gait analysis and the Timed Up and Go (TUG) test carried out using a wearable IMU located in the lower back. Results Individuals with cognitive impairments exhibit a peculiar gait pattern, characterized by significant reduction of speed (− 34% vs. healthy individuals), stride length (− 28%), cadence (− 9%), and increase in double support duration (+ 11%). Slight, but significant changes in stance and swing phase duration were also detected. Poorer performances in presence of cognitive impairment were observed in terms of functional mobility as overall and sub-phase TUG times resulted significantly higher with respect to healthy individuals (overall time, + 38%, sub-phases times ranging from + 22 to + 34%), although with some difference associated with age. The severity of mobility alterations was found moderately to strongly correlated with the ACE-R score (Spearman’s rho = 0.58 vs. gait speed, 0.54 vs. stride length, 0.66 vs. overall TUG time). Conclusion The findings obtained in the present study suggest that wearable IMUs appear to be an effective solution for the clinical assessment of mobility parameters of older persons screened for cognitive impairments within a clinical setting. They may represent a useful tool for the clinician in verifying the effectiveness of interventions to alleviate the impact of mobility limitations on daily life in cognitively impaired individuals.

Background: older adults from the Sardinian Blue Zone self-report low depressive symptoms and high psychological well-being. However, the role of dispositional resilience as a determinant of these characteristics is unknown. Objectives: the current study had three aims. First, to investigate associations among several putative predictors, including dispositional resilience and three established markers of positive and negative mental health. Second, to determine if gender differences in dispositional resilience, independent of age and cognitive impairment, are present in this population. Third, to examine the relative importance of the predictors of self-reported mental health and well-being. Methods: 160 elders were recruited in the Sardinian Blue Zone. The participants completed self-report measures of dispositional resilience, satisfaction with social ties, physical health, depressive symptoms, and psychological well-being. Results: trait resilience was significantly associated with predictors and markers of mental health. Males had significantly greater trait resilience. In regression analyses, dispositional resilience and satisfaction with social ties were significant predictors of all markers of mental health. Other factors were significantly associated only with certain markers. Conclusions: trait resilience and strong social ties appear to be key determinants of the high mental health of Sardinian Blue Zone older adults.

Objectives: The main aim of this study was to examine the impact of age-related changes on mental health, metacognitive, and motor functioning in late adulthood, while controlling for the effect of gender. Additionally, this investigation intended to study the association between motor efficiency indexes and self-reported psychological well-being, depression and cognitive failures over a period of 24 months. Design: Prospective longitudinal study: post hoc analysis. Participants: Ninety-one community-dwelling older participants (mean age = 78.7 years, SD = 5.6) were recruited in a rural village of the Sardinian Blue Zone – an area of exceptional longevity located in the central–eastern region of Sardinia, an Italian island in the Mediterranean Sea. Measurements: All respondents completed a battery of tests and questionnaires assessing motor and general cognitive efficiency, self-reported psychological well-being, negative affect, and cognitive failures. Results: The adoption of a multilevel modeling approach highlighted the significative impact of time on psychological well-being, as well as on mobility parameters like gait speed and cadence, while controlling for the gender effect. Overall, psychological well-being and motor swing significantly increase at follow-up, whereas the further above-mentioned measures decreased after 24 months. Moreover, compared to the national cut-off, at baseline and follow-up, participants reported higher perceived emotional well-being. Finally, significant relationships between motor scores and self-reported mental health and metacognitive measures were found both at baseline and follow-up. Conclusions: The maintenance of motor efficiency and preserved mental health seems to contribute to the successful aging of older people living in the Sardinian Blue Zone.

The main purpose of the present study was to compare the smoothness of gait in older adults with and without cognitive impairments, using the harmonic ratio (HR), a metric derived from trunk accelerations. Ninety older adults aged over 65 (age: 78.9 ± 4.8 years; 62% female) underwent instrumental gait analysis, performed using a wearable inertial sensor and cognitive assessment with the Mini Mental State Examination (MMSE) and Addenbrooke’s Cognitive Examination Revised (ACE-R). They were stratified into three groups based on their MMSE performance: healthy controls (HC), early and advanced cognitive decline (ECD, ACD). The spatio-temporal and smoothness of gait parameters, the latter expressed through HR in anteroposterior (AP), vertical (V) and mediolateral (ML) directions, were derived from trunk acceleration data. The existence of a relationship between gait parameters and degree of cognitive impairment was also explored. The results show that individuals with ECD and ACD exhibited significantly slower speed and shorter stride length, as well as reduced values of HR in the AP and V directions compared to HC, while no significant differences were found between ECD and ACD in any of the investigated parameters. Gait speed, stride length and HR in all directions were found to be moderately correlated with both MMSE and ACE-R scores. Such findings suggest that, in addition to the known changes in gait speed and stride length, important reductions in smoothness of gait are likely to occur in older adults, owing to early/prodromal stages of cognitive impairment. Given the peculiar nature of these metrics, which refers to overall body stability during gait, the calculation of HR may result in being useful in improving the characterization of gait patterns in older adults with cognitive impairments.

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This study evaluated the impact of the sociocultural context on dispositional optimism and resilience, life satisfaction, and religiosity in late adulthood. Moreover, the associations between those psychological measures and religiosity were investigated. Ninety-five older individuals recruited in the Sardinian Blue Zone and Cagliari completed a battery of tools assessing cognitive and mental health, and religiosity. Life satisfaction correlated with resilience and religiosity, whereas resilience correlated with optimism. Furthermore, participants of the rural area reported greater optimism and life satisfaction than peers living in the urban area. In conclusion, optimism and hedonic well-being favor optimal aging in the Blue Zone.

This study was conducted to investigate whether socio-cultural context (i.e., urban versus rural), perceived physical health, marital status, and satisfaction with family and non-family ties predicted hedonic and eudaimonic well-being in late adulthood and to examine the impact of the socio-cultural context on well-being, physical health and satisfaction with family and non-family ties by controlling age.One hundred and one community-dwelling participants aged between 68 and 94 were enrolled in the Sardinian Blue Zone—an area of exceptional longevity located in Sardinia, an Italian island in the Mediterranean Sea—and in the city of Cagliari—the regional capital. All participants completed a battery of tools assessing global cognitive efficiency, hedonic (i.e., SPANE and Satisfaction with Life Scales) and eudaimonic (i.e., Flourishing Scale) well-being, perceived physical health, and satisfaction with family and non-family ties. Hedonic and eudaimonic well-being were associated with several variables: marital status, socio-cultural context, and perceived physical health predicted 24% of the variance in the SPANE condition, 52% of the variance in the Satisfaction with Life condition was predicted by the socio-cultural context and satisfaction with family ties, whereas 39% of the Flourishing index was predicted by the socio-cultural context and physical health. Finally, the participants in the Sardinian Blue Zone reported better mental well-being and satisfaction with family and non-family ties than older people living in Cagliari. In conclusion, a socio-cultural context in which positive relationships in late adulthood are strengthened contributes to the promotion of mental health in late adulthood.