Aging & Longevity

Decreased telomerase expression, telomere shortening, senescence-associated markers, and inflammation have all been independently observed in the ageing brain and associated with disease. However, causality between limited telomerase expression and brain senescence and neuro-inflammation in the natural ageing setting is yet to be established. Here, we address these questions using the zebrafish as an ageing model. Akin to humans, zebrafish display premature ageing and death in the absence of...

Decreased trabecular meshwork (TM) cellularity is a critical pathogenic cause of primary open-angle glaucoma, yet therapies to regenerate the decellularized TM are very limited. Induced pluripotent stem cell-derived TM-like cells (iPSC-TM) can efficiently restore aqueous humor outflow. Here, we conducted a multi-modal RNA sequencing analysis to characterize the molecular mechanisms underlying TM regeneration. Our clustering analysis identified a group of iPSC-derived alpha6 integrin-positive...

Trees are integral to ecosystems and hold considerable economic importance. Their exceptional longevity and modular structure also make them valuable models for studying the long-term accumulation of somatic mutations and epimutations in plants. Empirical evidence indicates that the annual rate of these stochastic events correlates negatively with generation time, suggesting that species with long lifespans have evolved mechanisms to mitigate the build-up of deleterious somatic variants. It has...

Aging research has primarily focused on adult aging clocks, leaving a critical gap in understanding a biological clock across the full life cycle, particularly during infancy and childhood. Here we introduce LifeClock, a biological clock model that predicts biological age across all life stages using routine electronic health records and laboratory test data. To enhance individualized predictions, we integrated virtual patient representations from 24,633,025 heterogeneous longitudinal clinical...

The 70-kDa heat shock protein (Hsp70) chaperone is essential to maintain cellular protein homeostasis, facilitating the folding, assembly, membrane translocation and quality control of proteins. Hsp70s achieve their functions through 'selective promiscuity', interacting with a wide range of substrate proteins while minimizing undesired interactions. J-domain proteins (JDPs) and nucleotide exchange factors (NEFs) are key to substrate recognition, remodelling and release from chaperone complexes....

Across the evolutionary spectrum, sexual interactions can significantly influence the physiology and somatic aging in various species. In Caenorhabditis, male pheromones, sperm, and seminal fluid shorten the lifespan of hermaphrodites through different mechanisms. However, the specific male seminal fluid proteins responsible for this effect remain unidentified. Here, we find that several of the previously observed physiological changes in mated hermaphrodites require a newly-identified seminal...

CONCLUSION: In this study, it was found that quality of life decreased with increasing kinesiophobia, whereas quality of life increased with increasing level of successful aging. Longitudinal studies on quality of life in the elderly are recommended.

CONCLUSION: Our results imply that for those born small, having lower educational level is associated with having worse physical function at late-life, partly through less physical activity throughout the life-course.

CONCLUSIONS: Government-procured pDXA enables cost-effective universal OP screening in resource-limited rural areas. Scaling this model requires culturally adapted education (e.g., Wu Chinese dialect audiovisual materials) and tiered medication subsidies for groups with low medical payment capacity, aligning with the UN Decade of Healthy Aging (United Nations, UN Decade of Healthy Aging 2021-2030, World Health Organization, 2020).

Hippocampal degeneration is a feature of both normal aging and Alzheimer's disease (AD). Prior to macroscopic degeneration, microstructural changes occur such as demyelination, iron deposition, or subtle atrophy, which can be characterized in vivo using MRI. We topographically mapped measures of microstructure and macrostructure across the unfolded surface of the hippocampus in 224 healthy older adults at risk for AD (aged 57 to 87) and 37 younger adults (aged 18 to 37). We describe three...

In animal models, exposure to heightened maternal inflammation in utero is associated with altered offspring hippocampal development, including reduced dendritic arborization and density. However, the effects of prenatal maternal inflammation (PNMI) on offspring hippocampal microstructure in humans remain unclear. Here, we examined the relationship between exposure to PNMI and neurite density in the hippocampus and its subfields among offspring during late middle age. Participants included 72...

Altered β-amyloid (Aβ) homeostasis is a critical event triggering the shift from healthy aging to Alzheimer disease (AD) through the overproduction and impaired clearance of Aβ peptides. The Aβ-degrading enzymes (ADEs) are a collective group of proteases that normally promote clearance to counteract Aβ-induced neurodegeneration. We previously discovered that the beta-site amyloid precursor protein cleaving enzyme 1 is an atypical ADE that produces the nontoxic fragment Aβ34 by recognizing 40- or...

INTRODUCTION: Humans and other vertebrates exhibit anisotropic orientation and navigation skills, with better performances in the horizontal compared to the vertical plane. While horizontal navigation accuracy decreases with higher age, less is known about age effects on vertical spatial abilities. The same is true for disorders which cause spatial memory deficits, e.g., cognitive impairment or chronic peripheral vestibular loss.

Aging is characterized by chronic low-grade neuroinflammation, which increases the risk of neurodegenerative disorders. Neuroinflammation, driven by the activation of astrocytes and microglia, underlies age-associated cognitive deficits. Amplified neuroinflammatory responses to immune challenges are attributed to microglial activation in the aged brain. Despite extensive clinical and experimental evidence linking neuroinflammation to aging, the molecular players that control age-associated...

INTRODUCTION: White matter hyperintensity (WMH) is a hallmark imaging biomarker of cerebral small vessel disease and are strongly associated with vascular cognitive impairment in the elderly. Morphological changes in large extracranial brain-feeding arteries, such as the internal carotid (ICA) and vertebral arteries (VA), may alter intracranial hemodynamics and contribute to WMH development. This study examined the relationship between arterial tortuosity and WMHs using magnetic resonance...

Aging is characterized by a coordinated functional decline across multiple organs. While cell-autonomous mechanisms contribute to local aging phenotypes, the systemic synchronicity of aging suggests a major role for cell non-autonomous drivers. Emerging evidence implicates the hypothalamus-a central regulator of neuroendocrine and homeostatic functions-as a potential source of circulating pro-geronic signals. A hallmark of brain aging is the accumulation of senescent cells, particularly in...

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BackgroundPsychological disorders and cognitive impairment frequently co-occur in older adults, posing challenges to healthy aging. This study aimed to examine the association between late-life psychological disorders and the risk of developing cognitive impairment.MethodsProspective study analyzed data from 28,706 older adults enrolled in the Taipei City Older Adults Health Examination (2012-2016), among whom 10.3% developed cognitive impairment during follow-up. Psychological disorders were...

Population aging is accelerating, yet the multi-organ aging process and the geroprotective effects of dietary protein restriction (PR) remain poorly understood. Here, we conducted comprehensive proteomic analyses on 41 mouse tissues during male mouse aging and PR. Our findings identified tissue-specific aging hallmarks, including widespread changes in immunoglobulins and serine protease inhibitors across multiple tissues. PR mitigated age-related tissue-specific protein expression, epigenomic...

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