Aging & Longevity

No abstract

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...

Urbanization has introduced multiple factors that promote circadian clock dependent or independent disruption of physiology. Conditions such as late-night light (ALAN) exposure, shift working, cross-continental traveling may lead to circadian dysregulation leading to obesity, metabolic disorders and physiological alterations. As ALAN affects the circadian clock with concomitant effects on stress and free radical physiology, we hypothesised that night exposure to artificial light may affect the...

This cross-sectional investigation seeks to examine the association between dietary omega-3 fatty acids (including α-linolenic acid [ALA], eicosapentaenoic acid [EPA], and docosahexaenoic acid [DHA]) and biomarkers of cellular aging, specifically DNA methylation age (Horvathage) and telomere length (Horvathtelo), in older adults. Our analysis leveraged nationally representative data from 2,136 participants aged ≥ 50 years in the 1999-2002 NHANES cycles. Multivariable linear regression models...

Synthetic biology enabled the systematic engineering of bacteria for diverse applications, but their deployment in open environments raises concerns about their persistence and unintended ecological impacts. To address these challenges, genetic "expiry-date" circuits were designed to impose a tunable lifespan on bacteria. These circuits, structured as a feedforward activation network, regulate the timing of cell death by controlling the expression of Lysis E, enabling a programmed lifespan...

CONCLUSIONS: The MitoFit scientific communication was well received and should be considered in behavior change strategies that promote physical activity in community-dwelling older adults.

Controlled experiments suggest that the seasonal build-up of nitrogen (N) limitation constrains the responses of forest autumn phenology to elevated temperatures. Therefore, rising soil N is expected to increase the delaying effects of elevated temperature on the end of the season, i.e., leaf senescence. However, the interactive effects of temperature, soil N, and aridity on xylem autumn phenology remain unknown. We conducted a wide spatial analysis from 75 conifer sites in the Northern...

Immune aging is associated with decreased vaccine responses, but biomarkers for vaccine responsiveness remain unidentified. We analyzed immunotypes describing pre-vaccination immune cell profiles and their associations with triple vaccine responsiveness to influenza, pneumococcal, and SARS-CoV-2 vaccines in adults aged 25-78 years. Additionally, we developed an innovative measure, immune entropy, to quantify cumulative perturbations in the immune cell subset network. Specific immunotypes were...

An increasing number of physically active adults are taking the mTOR inhibitor rapamycin off label with the goal of extending healthspan. However, frequent rapamycin dosing disrupts metabolic health during sedentary conditions and abates the anabolic response to exercise. Intermittent once-weekly rapamycin dosing minimizes many negative metabolic side effects of frequent rapamycin in sedentary mice. However, it remains unknown how different rapamycin dosing schedules impact metabolic, physical,...

Micro/nanoplastics (MNPs), pervasive environmental pollutants, accumulate in cardiovascular tissues and drive premature aging through multiscale pathophysiological cascades. This review synthesizes evidence establishing environmental phenotypic aging as a novel mechanistic link between MNP exposure and cardiovascular senescence. MNPs induce mitochondrial damage involving cristae disruption and mtDNA leakage activating cGAS-STING, epigenetic reprogramming encompassing METTL3-mediated m6A...

Our brain is bathed in cerebrospinal fluid (CSF) that is produced by the choroid plexus. CSF serves as a dispersion route for hormones and nutrients, and a conduit for waste clearance. Age-dependent reduction in the CSF secretion rate could influence cerebral waste clearance and thereby promote cognitive deficits in the elderly. Here, we resolve age-dependent modulation of CSF dynamics and choroid plexus function by complementary in vivo determinations of intracranial pressure (ICP) and CSF...

Nipah virus (NiV) causes a severe neurological disease in humans. The first NiV outbreak, in Malaysia, involved pig-to-human transmission, that resulted in significant economic losses to the local pig industry. Despite the risk NiV poses to pig-dense regions, no licensed vaccines exist. This study therefore assessed three NiV vaccine candidates in pigs: (1) adjuvanted soluble NiV (s)G protein, (2) adjuvanted pre-fusion stabilised NiV (mcs)F protein, and (3) adenoviral vectored NiV G (ChAdOx1 NiV...

Gut microbiota (GM) is implicated in aging biology, yet its dual regulatory role in the distinct yet interconnected processes of lifespan extension and aging remains poorly understood. This study employed genetic approaches to identify GM taxa exerting causal effects on longevity and aging and assess the mediation role of cerebrospinal fluid (CSF) proteins. We leveraged summary statistics of the GM taxa (207 taxa, 7738 participants from the Dutch Microbiome Project), the CSF proteins (7008...