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Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly 1 , 2 . To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1 , which encodes a crucial DNA repair protein 3 , 4 , in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence 5 – 7 in the immune system only. We show that Vav-iCre +/− ;Ercc1 −/fl mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice 8 – 10 . Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre +/− ;Ercc1 −/fl or aged wild-type mice into young mice induced senescence in trans , whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre +/− ;Ercc1 −/fl mice with rapamycin reduced markers of senescence in immune cells and improved immune function 11 , 12 . These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing. An aged, senescent immune system has a causal role in driving systemic ageing, and the targeting of senescent immune cells with senolytic drugs has the potential to suppress morbidities associated with old age.

For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan. The milestones that mark the advances in ageing research, the medical, commercial and societal implications of ageing and the different ageing pathways and processes that are associated with ageing are discussed.

The skin, being the barrier organ of the body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found to accumulate with age and may contribute to age-related skin changes and pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on skin aging. By affecting molecular pathways of senescence, polyphenols are able to prevent or delay the senescence formation and, consequently, avoid or ameliorate aging and age-associated pathologies of the skin. This review aims to provide an overview of the current state of knowledge in skin aging and cellular senescence, and to summarize the recent in vitro studies related to the anti-senescent mechanisms of natural polyphenols carried out on keratinocytes, melanocytes and fibroblasts. Aged skin in the context of the COVID-19 pandemic will be also discussed.

Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.

Purpose of ReviewThe aim of this review is to summarize current conceptual models of cognitive reserve (CR) and related concepts and to discuss evidence for these concepts within the context of aging and Alzheimer’s disease.Recent FindingsEvidence to date supports the notion that higher levels of CR, as measured by proxy variables reflective of lifetime experiences, are associated with better cognitive performance, and with a reduced risk of incident mild cognitive impairment/dementia. However, the impact of CR on longitudinal cognitive trajectories is unclear and may be influenced by a number of factors. Although there is promising evidence that some proxy measures of CR may influence structural brain measures, more research is needed.SummaryThe protective effects of CR may provide an important mechanism for preserving cognitive function and cognitive well-being with age, in part because it can be enhanced throughout the lifespan. However, more research on the mechanisms by which CR is protective is needed.

The locus coeruleus (LC), the origin of noradrenergic modulation of cognitive and behavioral function, may play an important role healthy ageing and in neurodegenerative conditions. We investigated the functional significance of age-related differences in mean normalized LC signal intensity values (LC-CR) in magnetization-transfer (MT) images from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort - an open-access, population-based dataset. Using structural equation modelling, we tested the pre-registered hypothesis that putatively noradrenergic (NA)-dependent functions would be more strongly associated with LC-CR in older versus younger adults. A unidimensional model (within which LC-CR related to a single factor representing all cognitive and behavioral measures) was a better fit with the data than the a priori two-factor model (within which LC-CR related to separate NA-dependent and NA-independent factors). Our findings support the concept that age-related reduction of LC structural integrity is associated with impaired cognitive and behavioral function. Alterations of locus coeruleus signal intensity have been associated with functional changes in health and disease. Here, the authors tested a pre-registered hypothesis on a large number of subjects as part of the Cam-CAN consortium.

The unprecedented increase in life expectancy presents a unique opportunity and the necessity to explore both healthy and pathological aspects of ageing. Electroencephalography (EEG) has been widely used to identify neuromarkers of cognitive ageing due to its affordability and richness in information. However, despite the growing volume of data and methodological advancements, the abundance of contradictory and non‐reproducible findings has hindered clinical translation. To address these challenges, our study introduces a comprehensive workflow expanding on previous EEG studies and investigates various static and dynamic power and connectivity estimates as potential neuromarkers of cognitive ageing in a large dataset. We also assess the robustness of our findings by testing their susceptibility to band specification. Finally, we characterise our findings using functionally annotated brain networks to improve their interpretability and multi‐modal integration. Our analysis demonstrates the effect of methodological choices on findings and that dynamic rather than static neuromarkers are not only more sensitive but also more robust. Consequently, they emerge as strong candidates for cognitive ageing neuromarkers. Moreover, we were able to replicate the most established EEG findings in cognitive ageing, such as alpha oscillation slowing, increased beta power, reduced reactivity across multiple bands, and decreased delta connectivity. Additionally, when considering individual variations in the alpha band, we clarified that alpha power is characteristic of memory performance rather than ageing, highlighting its potential as a neuromarker for cognitive ageing. Finally, our approach using functionally annotated source reconstruction allowed us to provide insights into domain‐specific electrophysiological mechanisms underlying memory performance and ageing. Highlights We provide an open and reproducible pipeline with a comprehensive workflow to investigate static and dynamic EEG neuromarkers. Neuromarkers related to neural dynamics are sensitive and robust. Individualised alpha power characterises cognitive performance rather than ageing. Functional annotation allows cross‐modal interpretation of EEG findings. We analysed a large open resting‐state EEG dataset and found that dynamic rather than static neuromarkers better capture cognitive ageing. We clarified that individualised alpha power reflects memory performance rather than ageing. Finally, we used functionally annotated source reconstruction to reveal domain‐specific electrophysiological mechanisms underlying memory performance and ageing.

•Greater annual rates of memory decline were associated with greater volume loss in multiple temporal and occipital regions.•Decline in verbal fluency was associated with greater ventricular size and decline in frontal, temporal, and parietal regions.•Decline in visuospatial ability was associated with volume loss in 3 temporal and parietal regions.•Declines in Trail-Making Test-A were associated with volume loss in 4 temporal and parietal regions.•Declines in Trail-Making Test-B were associated with ventricular size and volume loss in 10 regions. Investigation of relationships between age-related changes in regional brain volumes and changes in domain-specific cognition could provide insights into the neural underpinnings of individual differences in cognitive aging. Domain-specific cognition (memory, verbal fluency, visuospatial ability) and tests of executive function and attention (Trail-Making Test Part A and B) and 47 brain volumes of interest (VOIs) were assessed in 836 Baltimore Longitudinal Study of Aging participants with mean follow-up of 4.1 years (maximum 23.1 years). To examine the correlation between changes in domain-specific cognition and changes in brain volumes, we used bivariate linear mixed effects models with unstructured variance-covariance structure to estimate longitudinal trajectories for each variable of interest and correlations among the random effects of these measures. Higher annual rates of memory decline were associated with greater volume loss in 14 VOIs primarily within the temporal and occipital lobes. Verbal fluency decline was associated with greater ventricular enlargement and volume loss in 24 VOIs within the frontal, temporal, and parietal lobes. Decline in visuospatial ability was associated with volume loss in 3 temporal and parietal VOIs. Declines on the attentional test were associated with volume loss in 4 VOIs located within temporal and parietal lobes. Greater declines on the executive function test were associated with greater ventricular enlargement and volume loss in 10 frontal, parietal, and temporal VOIs. Our findings highlight domain-specific patterns of regional brain atrophy that may contribute to individual differences in cognitive aging.

Background Population aging is one of the most significant global demographic changes of the 21st century, driven by increased life expectancy and declining fertility rates. This phenomenon presents both achievements and challenges for public health systems worldwide. Aims On the one hand, advances in healthcare and socio-economic conditions have contributed to longer lives and improved quality of life for older adults. On the other hand, aging populations are increasingly affected by chronic diseases, greriatric syndromes, and multimorbidity, leading to greater healthcare demands and higher associated costs. Methods This manuscript explores evidence on regards of the impact of aging on healthcare and economic systems, emphasizing the need for a paradigm shift toward healthy aging. Results Healthy aging, as defined by the World Health Organization, focuses on the maintenance of intrinsic capacity, physical, mental, and social well-being throughout life. It highlights the importance of preventive healthcare, proper nutrition, and regular physical activity in delaying the onset of chronic conditions and maintaining functional independence. Furthermore, the manuscript addresses the challenges faced by healthcare infrastructures and pension systems as they adapt to aging populations, with particular attention to the strain caused by workforce shortages and the rising need for long-term care. Discussion A coordinated public health approach is essential to promote healthy aging and mitigate the economic and societal impacts of population aging. Conclusions This paper underscores the need for integrated health policies and multidisciplinary care models to ensure that longer life expectancy is accompanied by better quality of life for older individuals.

Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This mini-review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment, which contributes to decline of human skin function.