Aging & Longevity

Aging is a risk factor for severe COVID-19, characterized by vascular endothelial dysfunction. Although possible susceptibility of vascular endothelial cells (ECs) to SARS-CoV-2 infection has been suggested, the details of entry into cells have not been clarified. Previously, we reported that in an aged mouse model of severe COVID-19, ECs show a massive viral uptake and inflammatory response. Here, we focused on the endocytic capacity of senescent ECs. We found that the senescent ECs showed high...

As memories age, their immediate retrievability decreases albeit, due to ongoing memory consolidation, their future rate of forgetting weakens. Here, we show in two experiments (N = 1.216 participants) that mentally traveling back in time to older memories' temporal context at encoding reverses the two effects and makes the memories similar again to how they were at an earlier point in time. Mental time travel increased both the memories' immediate retrievability and their future rate of...

Age-related structural and functional deterioration of the kidneys is common among elderly individuals and contributes to increased mortality and morbidity. Mitochondrial dysfunction and cellular senescence are two hallmarks of aging that drive a progressional renal decline; however, the underlying molecular mechanisms and endogenous regulators behind these processes remain incompletely understood. The metabolism of polyunsaturated fatty acids by CYP450 enzymes produces numerous bioactive lipid...

Benign prostatic hyperplasia (BPH) is an age-related condition characterized by progressive prostate enlargement driven in part by the accumulation of senescent epithelial cells and their pro-inflammatory secretome. Using human single-cell RNA sequencing and laser capture microdissection, we identified C-X-C Motif Chemokine Ligand 13 (CXCL13) as a key chemokine secreted by senescent prostate epithelial cells. CXCL13 recruits CD4^(+) T cells via the C-X-C Chemokine Receptor Type 5 (CXCR5)...

Background Minor and major neurocognitive disorders, depression, and anxiety are common in older adults. The brain and specifically the aging brain, relies heavily on oxygen and is highly sensitive to reductions in oxygen availability. Hypoxia occurs during both acute and prolonged exposure to altitude. While the negative effects of very low oxygen levels at high altitudes (above 3500 m) on cognition and symptoms of depression as well as anxiety are well-documented, we propose that moderate...

Proteins are the cornerstone of life. However, the proteomic blueprint of aging across human tissues remains uncharted. Here, we present a comprehensive proteomic and histological analysis of 516 samples from 13 human tissues spanning five decades. This dynamic atlas reveals widespread transcriptome-proteome decoupling and proteostasis decline, characterized by amyloid accumulation. Based on aging-associated protein changes, we developed tissue-specific proteomic age clocks and characterized...

Adult neurogenesis is defined as the process by which new neurons are produced from neural stem cells in the adult brain. A comprehensive understanding of the mechanisms that regulate this process is essential for the development of effective interventions aimed at decelerating the decline of adult neurogenesis associated with ageing. Mathematical models provide a valuable tool for studying the dynamics of neural stem cells and their lineage, and have revealed alterations in these processes...

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CONCLUSIONS: Higher sleep quality was significantly associated with a reduced risk of osteoporosis among older adults. These findings suggest that sleep quality may be a potentially modifiable behavioral factor related to osteoporosis risk, warranting further investigation in future longitudinal and interventional studies.

There is a need to study dementia risk factors more equitably across high-income countries (HICs) and low- and middle-income countries (LMICs). Cohort Studies of Memory in an International Consortium (COSMIC) is doing this by bringing together cohort studies of cognitive ageing from around the world to study dementia risk factors in a truly international way. COSMIC researchers have investigated a wide range of dementia risk factors across the diverse member studies and shown that some factors...

CONCLUSIONS: The findings suggest that while lower levels of dementia-related fear may be linked to increased motivation for engaging in risk reduction behaviors, elevated levels of fear do not appear to support such engagement. Rather than emphasizing the negative impacts of dementia, public health strategies should empower individuals with actionable messages to engage in dementia risk reduction behaviors.

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White matter hyperintensities (WMH) are associated with cortical thinning in distant brain regions. However, it is currently unclear how WMH affect neurodegeneration in early Alzheimer's disease (AD). Here, we investigated associations between WMH and cortical thickness in temporal regions involved in early AD (AD cortical signature), while correcting for regional amyloid and tau accumulation assessed by PET. We performed cross-sectional (n = 551), and longitudinal (n = 125) analyses in older...

Alterations in mitochondrial ultrastructure and reduced levels of the crista-shaping protein Opa1 are key features of mitochondrial myopathies and aging. We identify and characterize a biological therapy that improves mitochondrial and disuse myopathy models by boosting Opa1 levels. In silico analysis identifies microRNAs (miRNAs) 128-3p and 148/152-3p family as conserved modulators of OPA1 transcription and elevated in various muscle disorders. These miRNAs target the 3' UTR of murine and human...

Gerascophobia-the excessive fear of aging-is linked to health anxiety and negative body perceptions. While health anxiety may heighten aging-related fears, body image satisfaction may buffer this effect. However, their interplay remains underexplored, particularly among community-dwelling middle-aged and older adults not receiving psychological care. This study aims to examine the predictive role of health anxiety on gerascophobia and assess whether body image satisfaction moderates this...

Education is related to a wide variety of beneficial health, behavioral, and societal outcomes. However, whether education causes long-term structural changes in the brain remains unclear. A pressing challenge is that individuals self-select into continued education, thereby introducing a wide variety of environmental and genetic confounders. Fortunately, natural experiments allow us to isolate the causal impact of increased education from individual (and societal) characteristics. Here, we...

Despite the increasing availability of biomarkers in clinical settings, diagnosing individuals with subtle cognitive/behavioral symptoms and normal structural brain imaging remains challenging. In real-world settings, it is not feasible to subject all such patients to costly and invasive second-level assessments, and there are no clear guidelines for identifying those who should undergo these procedures beyond clinical follow-up and structural imaging. The present study explores the potential of...

In this issue of Neuron, Graves et al.¹ report that genetically reducing senescent cells by deleting p16 in a tauopathy mouse model significantly lessens tau pathology, neurovascular dysfunction, and behavioral deficits. Their study highlights the crucial role of p16-dependent senescence in microglia and endothelial cells as active drivers of neurodegeneration.

The human cortex exhibits remarkable morphometric similarity between regions; however, the form and extent of lifespan network remodeling remain unknown. Here, we show the spatiotemporal maturation of morphometric brain networks, using multimodal neuroimaging data from 33,937 healthy participants aged 0-80 years. Global architecture matures from birth to early adulthood through enhanced modularity and small worldness. Early development features cytoarchitecturally distinct remodeling: sensory...

Stem cells maintain tissue architecture by replacing differentiated cells at steady state and upon injury. Implementing this cornerstone role requires protection of stem cells from pathogens and from the toxic effects of immune system activation. However, the pro-inflammatory innate immune mechanisms that protect differentiated cells from infection are poorly functional in stem cells. Instead, stem cells employ other specific defence mechanisms, such as antiviral RNA interference. At steady...