Alzheimer’s disease (AD) and related dementias are closely associated with alterations in microglial states. These microglial changes occur in response to amyloid-β (Aβ) accumulation and aberrant tau phosphorylation and can either protect against or exacerbate AD progression, depending on factors such as disease stage, genetic background, and environmental influences. This review focuses on recent advances in understanding the protective functions and features of microglia during the early stages of AD, while highlighting the outstanding questions regarding how these protective states deteriorate and become dysfunctional as the disease progresses. Interestingly, epidemiological studies have suggested an inverse relationship between AD and cancer incidence, and in this context, we provide a comparative analysis of microglial phenotypes in AD and cancer to speculate on how insights from anti-tumor microglia may inspire new strategies for reprogramming microglia to combat AD and related dementias.

Aims: This study aimed to characterise the natural killer (NK; CD3^-CD16⁺CD56⁺) and monocyte compartments in 54 participants by analysing absolute cell counts in relation to age, sex, cytomegalovirus (CMV) serostatus, an established marker of immune ageing, and interleukin-6 (IL-6) values, as an indicator of inflamm-ageing.

Methods: The analysis was conducted in a cohort of Sicilians (28 females and 26 males) aged 19-110 years, including 20 adults (19-64 years), 15 older adults (68-88 years), 11 long-living individuals (93-104 years), and 8 semi- and supercentenarians (105-110 years; hereafter referred to as the oldest centenarians). Multiple negative binomial regression models were used to assess the independent effects of age, sex, CMV serostatus, and IL-6 concentrations on NK and monocyte counts.

Results: Although NK cells and monocytes are generally reported to increase with age, adjustment for covariates revealed that NK cell counts showed only a non-significant age-related trend. In contrast, no statistically significant independent association with age was detected for monocytes. A statistically significant sex effect emerged, with men exhibiting higher NK cell counts than women. Monocyte counts were significantly and positively associated with IL-6 levels.

Conclusion: These findings suggest that previously reported associations of advanced age, particularly extreme longevity, with higher NK-cell and monocyte counts may not be independent of sex, in the case of NK cells, or of chronic low-grade inflammation, as reflected by IL-6 levels, in the case of monocytes. Given the observational design, these results should be interpreted as adjusted associations rather than evidence of mediation or causality.

Over decades, nomenclature in erythrocyte cell death research has been unrefined. Recently, several attempts have been made to adapt the nomenclature suggested by the Nomenclature Committee on Cell Death (NCCD) guidelines to erythrocytes. Within the framework of the standardization of terms used in erythrocyte cell death studies, erythrocyte senescence and eryptosis, a regulated cell death of erythrocytes, have been defined and the formal distinction between both events has been recently established. Differences in their physiological role have been underscored, and markers that can be used to distinguish between erythrocyte senescence and eryptosis have been identified. As a further step, we aim to dissect cellular senescence in nucleated cells and erythrocytes, identifying their hallmarks, key triggers, molecular mechanisms, immunity-related effects, as well as physiological aspects. Available evidence suggests that cellular senescence in nucleated cells can be considered an active biological program, while erythrocyte senescence rather reflects a more passive, gradual accumulation of cellular damage. Fundamental mechanism-based and physiological differences between senescence in nucleated cells and erythrocytes highlighted in this mini-review indicate that the use of the term ‘erythrocyte senescence’ should be discouraged as misleading. Instead, the term ‘erythrocyte aging’ might be more appropriate.

Somatic mutations accumulate in tissues throughout life and are increasingly being recognized as contributors to aging. While their role in cancer has been extensively characterized, their occurrence and functional impact in the cardiovascular system remain poorly understood, partly due to technical limitations in detecting low-frequency and cell-specific variants. Recent advances in single-cell sequencing have begun to unveil how somatic mutations accumulate both in vascular resident cells, including vascular smooth muscle cells, and in circulating hematopoietic cells, such as those associated with clonal hematopoiesis of indeterminate potential. Both resident vascular cells and infiltrating immune cells harboring clonally expanded somatic mutations may influence vascular pathology. This mini-review summarizes the current knowledge on somatic mutation accumulation in the vasculature, focusing on recent studies and the techniques applied for their detection. In addition, we discuss emerging evidence for the functional relevance of somatic mutations in aging and age-related vascular disease.

Cardiovascular aging is characterized by progressive loss of regulatory capacity, reduced physiological reserve, and increased vulnerability to stress and disease. Resting heart rate (RHR) and heart rate variability (HRV) provide complementary measures of cardiac automaticity and autonomic regulation, capturing important dimensions of cardiovascular aging. Comparative and epidemiological evidence demonstrates that elevated RHR and reduced HRV predict morbidity and mortality across species and human populations, reflecting cumulative physiological stress and declining regulatory function. Biological pathways associated with these autonomic phenotypes include sympathetic overactivation, parasympathetic withdrawal, neuroendocrine dysregulation, impaired baroreflex function, chronic inflammation, oxidative stress, and mitochondrial dysfunction. Clinical and mechanistic studies indicate that behavioral interventions (e.g., exercise and dietary modulation), pharmacological therapies, and neuromodulatory approaches can favorably influence RHR and HRV, although their causal effects on aging trajectories remain uncertain. Recent advances in wearable technologies and machine-learning-based phenotyping enable continuous assessment of autonomic function in both research and real-world settings. Integrating RHR and HRV into geroscience frameworks may help link autonomic regulation with fundamental aging mechanisms and cardiovascular risk. As accessible, noninvasive measures of physiological resilience and adaptability, RHR and HRV have potential value for advancing precision approaches to healthy cardiovascular aging and longevity.