Aging & Longevity

Using multi-echo blood oxygenation level-dependent (BOLD) neuroimaging, we examined lifespan differences in three subcortical nuclei important to the neuromodulation of cognition and target sites for early Alzheimer's pathogenesis in the isodendritic core: the locus coeruleus (LC) the major source of noradrenaline, the nucleus basalis of Meynert (NBM) the major source of acetylcholine, and the ventral tegmental area (VTA) the major source of dopamine. Seventy-one participants, from 19 to 86...

CONCLUSIONS AND IMPLICATIONS: Within this prospective cohort analysis, low CC emerged as a new independent risk factor for incident sarcopenia over 3 years, with a concomitant escalation in risk observed with severe diminution of CC.

The intensive production and use of plastics, poor biodegradability and inadequate recycling have caused excessive and alarming environmental pollution. This has led to the inevitable intake by humans, through different routes, of small plastic particles, the micro and nano-plastics (MNPs) with sizes ranging from nanometers (<1000 nm) to micrometers (from 5 mm to 1 µm). MNPs can cause harmful effects in human tissues and organs, contributing to the early onset of aging and various age-related...

Given the growing global elderly population and the accelerating decrease in grey matter volume (GMV) with age, understanding healthy brain aging is increasingly important. This study investigates whether variations in modifiable traits can account for differences in GMV and whether these traits can inform strategies to mitigate risks of future brain disorders. We identified 66 traits significantly associated with total GMV. Further, we examined the joint contributions of different domain traits...

Ageing is a prevalent characteristic of all cells, tissues, and organs; certain ones, such as the ovaries, undergo significant ageing and do so early in the lifespan of mammals. Despite the widely recognized hormonal regulation occurring in the ovaries, numerous mechanisms influencing ovarian ageing remain unclear. Recently, a long-overlooked consequence of splicing, small RNA molecules, characterized by their circular structure, have gained attention. Circular RNAs (circRNAs) have been...

The misclassification of functional genomic loci as pseudogenes has long obscured critical regulators of cellular homeostasis, particularly in aging-related pathways. One such locus, originally annotated as RPL29P31, encodes a 17-kDa protein now redefined as PERMIT (Protein that Mediates ER-Mitochondria Trafficking). Through rigorous experimental validation-including antibody development, gene editing, lipidomics, and translational models-p17/PERMIT has emerged as a previously unrecognized...

CONCLUSION: GS research is transitioning from fundamental mechanisms to clinical diagnostics and therapeutics. Future advancements necessitate the integration of multimodal imaging technologies and interdisciplinary collaboration to facilitate early AD diagnosis and therapeutic target development. This study represents the first systematic construction of a knowledge framework for this field, providing theoretical foundations for optimizing research strategies and translational pathways.

INTRODUCTION: The entorhinal cortex (EC)-hippocampus system is critical for memory and affected early in Alzheimer's disease (AD). Cognitive dysfunction in AD is linked to neuropathological changes, including non-heme iron accumulation in vulnerable brain regions. This study characterized iron distribution in the EC-hippocampus system using ultra-high field (UHF) magnetic resonance imaging (MRI) at 7 Tesla (T) in aging and mild cognitive impairment (MCI), an AD at-risk state.

The increasing prevalence of neurodegenerative diseases in an aging population underscores the critical need for reliable biomarkers distinguishing normal aging from pathological neurodegeneration. This study leverages neuroimaging to identify age-resilient biomarkers, establishing a baseline of neural features that are relatively stable across the aging process. Our research objectives are threefold: (a) Validate a methodology using leverage scores to identify age-robust neural signatures; (b)...

CONCLUSION: Increased arterial stiffness and reduced CBF were not independently associated with smaller HV. However, in combination, persistently elevated AS and reduced CBF is associated with smaller HV. These effects were equally exerted across all hippocampal subfields tested. Our findings suggest a lag effect in the arterial stiffness and hippocampal volume relationship. We propose that the subsequent reduction in cerebral blood flow observed with elevated arterial stiffness may be the...

Evidence indicates that the integrity of in utero development influences late life healthy or unhealthy aging; however, specific links between them are unclear. Histone chaperone HIRA is thought to play a role in both life stages, and here, we explore this role using the murine pigmentary system by investigating and comparing the effects of its lineage-specific knockout, either conditionally during embryogenesis or postnatally. Embryonic knockout of Hira in tyrosinase+ neural crest-derived...

The nuclear chromatin landscape changes with age. Here, we investigate whether chromatin alterations distinguish also animals with unusual aging rates, focusing on Caenorhabditis elegans with reduced insulin/IGF-like signaling (IIS), i.e., daf-2 mutants. In these animals, enhancer regions that close with age tend to open and become transcriptionally active. We identify LIN-39 as a transcription factor (TF) binding these regions and being required for the longevity of daf-2 mutants. LIN-39 acts...

The utilization of artificial intelligence in studying the dysregulation of gene expression in Alzheimer's disease (AD) affected brain tissues remains underexplored, particularly in delineating common and specific transcriptomic signatures across different brain regions implicated in AD-related cellular and molecular processes, which could help illuminate novel disease biology for biomarker and target discovery. Herein we developed a deep learning framework, which consisted of multi-layer...

To gain a comprehensive, unbiased perspective on molecular changes in the brain that may underlie the need for sleep, we have characterized the transcriptomes of single cells isolated from rested and sleep-deprived flies. Here we report that transcripts upregulated after sleep deprivation, in sleep-control neurons projecting to the dorsal fan-shaped body^(1,2) (dFBNs) but not ubiquitously in the brain, encode almost exclusively proteins with roles in mitochondrial respiration and ATP synthesis....

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Accumulation of senescent cells is closely linked with intervertebral disc (IVD) degeneration, a prevalent age-dependent chronic disorder causing low back pain. While previous studies have highlighted that platelet-derived growth factor (PDGF) mitigated IVD degeneration through anti-apoptotic and pro-anabolic effects, its impact on IVD cell senescence remains elusive. In this study, human NP and AF cells derived from aged, degenerated IVDs were treated with recombinant human (rh) PDGF-AB/BB for...

CONCLUSION: Lower heel eBMD is independently associated with increased dementia risk among older adults.

Microglia are the brain's resident immune cells known for their dynamic responses to tissue and vascular injury. However, few studies have explored how microglial activity differs across the life stages of early development, adulthood, and aging. Using two-photon live imaging, we confirm that microglia in the adult cerebral cortex exhibit highly ramified processes and relatively immobile somata under basal conditions. Their responses to focal laser-induced injury occur over minutes and are...

Vacuolar acidification is crucial for the homeostasis of intracellular pH and the recycling of proteins and nutrients in cells, thereby playing important roles in various physiological processes related to vacuolar function. The key factors regulating vacuolar acidification and underlying mechanisms remain unclear. Here, we report that Arabidopsis phospholipase Dζ2 (PLDζ2) promotes the acidification of the vacuolar lumen to stimulate autophagic degradation under phosphorus deficiency. The pldζ2...

Training has emerged as a promising materials design technique in which function can be achieved through repeated physical modification of an existing material rather than by direct chemical functionalization, cutting, or reprocessing. This work investigates both the ability to train for function and then to erase that function on-demand in macroscopic metamaterials made from liquid crystal elastomers. We first show that the Poisson's ratio of these disordered arrays can be tuned via directed...