Aging & Longevity

CONCLUSION: Systemic inflammation and metabolic dysregulation were associated with poorer cognitive performance, particularly executive dysfunction, in this rural aging cohort. These findings, while modest in effect size, support the importance of cardiometabolic health in cognitive aging, motivating future longitudinal and mechanistic studies.

CONCLUSION: The Adgrl2-Camk2d-TRPV1 signaling axis is a core driver pathway of perimenopausal cognitive impairment, exacerbating neuronal damage by mediating calcium overload, neuroinflammation, and metabolic disorders. This discovery provides a novel pathological mechanism for perimenopausal cognitive impairment, identifies Adgrl2 and TRPV1 as potential therapeutic targets, and designates Ca^(2+) as an ideal diagnostic biomarker, offering significant support for clinical diagnosis, treatment,...

In Hutchinson-Gilford progeria syndrome (HGPS), dysfunctional autophagy results in the accumulation of progerin, a lamin A mutant variant that alters a plethora of processes, inducing senescence and driving premature aging. Therefore, the elimination of progerin through autophagy restoration emerges as a therapeutic intervention against HGPS. However, a comprehensive study of autophagy flux in HGPS remains to be addressed. In this study, the dynamics of autophagy in HGPS fibroblasts were...

Sensory impairment (SI) and accelerated epigenetic aging are both linked to later-life vulnerability, yet their joint value for risk stratification remains poorly understood. We investigated whether the co-occurrence of sensory deficits and accelerated epigenetic aging identifies older adults at heightened risk of functional decline and mortality. We analyzed data from 2,395 participants in the 2016 wave of the Health and Retirement Study with valid DNA methylation (DNAm) and sensory data....

Fractures of long bones such as the femur are a common and serious health concern in the elderly, triggering immune responses essential for healing but also affecting remote organs like the liver. With age, the risk of fractures and immune imbalance increases, raising the likelihood of organ damage, infections, and mortality. To better understand age-dependent hepatic responses to bone injury, this study investigates early immune responses in the liver following femoral osteotomy, used here as a...

Epigenetic clocks are widely used to estimate biological age and predict health outcomes, but their translational value depends not only on accuracy but also on reliability. Using the TranslAGE platform, we evaluated both technical and biological reliability across 18 DNA methylation-based aging biomarkers, including chronological, mortality, and pace-of-aging clocks. Most clocks demonstrated excellent technical reproducibility across replicate assays on EPIC and 450 K arrays. However, several...

Mitochondrial dysfunction drives T cell aging in mice. Yet, due to fundamental differences in T cell aging mechanisms between species, whether human T cells exhibit similar mitochondrial alterations remains unclear, with existing evidence often conflicting. Using cryoelectron tomography, we resolved the structure and spatial organization of mitochondrial ribosomes in primary human CD8^(+) T cells under physiological conditions. Comparative analysis with human aging models revealed an age-related...

Membrane separation technology represents a promising and effective alternative to traditional energy-intensive gas separation technologies. However, most commercial membranes have low permeability and moderate selectivity, which limits their ability to meet the stringent gas purity requirements for hydrogen purification and natural gas upgrading. In this study, Matrimid, a widely used commercial polymer, was selected as the matrix material. Cucurbituril (CB) with selective cavity was...

The buried interface between the self-assembled monolayers (SAMs) and the perovskite plays a critical role in device performance and stability in inverted perovskite solar cells (PSCs). However, severe desorption and agglomeration of self-assembled molecules lead to interfacial losses and shorten device longevity. Herein, we design a molecule, 5,5',5″-(nitrilotri-4,1-phenylene)tris[2-thiophenecarboxylic acid] (TTA) with a noncoplanar molecular configuration and multiple functional groups. The...

The aging brain exhibits a decline in the regenerative populations of neural stem cells (NSCs). While mechanisms that restore old NSC function have started to be identified, the role of lipids-especially complex lipids-in NSC aging remains largely unclear. Using lipidomic profiling by mass spectrometry, we identify age-related changes in complex lipids in quiescent NSCs in vitro and in vivo. Moreover, several polyunsaturated fatty acids increase across lipid classes in quiescent NSCs during...

The 9p21 locus encodes critical cell cycle regulators p16^(INK4A), p14^(ARF), and p15^(INK4B) and contains a high density of SNPs associated with aging-related diseases. Progress toward understanding 9p21 regulatory mechanisms has been constrained by complex transcript structures and a shortage of cell models that retain physiologic locus control. We innovated tools to deconvolve the expression and regulation of 9p21 transcripts in single cells. We find that 9p21 transcripts exhibit highly...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Familial AD accounts for less than 1% of cases, while sporadic AD (SAD) accounts for over 95%. Mild cognitive impairment (MCI) is the critical transition phase from normal aging to AD dementia. Understanding the pathological progression from MCI to AD and the mechanisms underlying SAD is essential. Rodent models, including transgenic and non-transgenic models, are vital tools for developing effective AD therapies. However,...

Sarcopenia and cognitive decline frequently co-occur in older adults, and growing evidence indicates that these conditions share a common biological substrate centred on the muscle-brain axis. In this narrative review we synthesise contemporary mechanistic and translational evidence on how skeletal muscle communicates with the ageing brain through myokines and exerkines - including irisin/FNDC5, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1),...

Aging is characterized by progressive physiological decline and accumulation of senescent cells that drive chronic "inflammaging" through the senescence-associated secretory phenotype (SASP). The complement system, traditionally viewed as a systemic extracellular defense mechanism, is now recognized as an essential intracellular network (the complosome). This review synthesizes current research on how intracellular C3 (intC3), and intracellular C5 (intC5) in certain contexts engage in extensive...

The human microbiome profoundly influences host physiology, metabolism, and immune function. A balanced microbial ecosystem supports immune homeostasis and health, whereas dysbiosis contributes to diverse diseases, including metabolic, autoimmune, neurodegenerative, and infectious disorders. Aging, the greatest risk factor for chronic disease, is characterized by hallmarks such as mitochondrial dysfunction, genomic instability, and "inflammaging," a state of chronic low-grade inflammation....

Healthy and pathological aging are associated with progressive changes in cortical inhibition, yet the underlying neural mechanisms remain incompletely understood. Somatosensory gating (SG), the brain's suppression of redundant tactile input, provides a pre-attentive marker of inhibitory function. Paired-pulse paradigms concurrent with noninvasive magnetoencephalography (MEG) provide a millisecond portrayal of the neural dynamics underlying somatosensory processing and the gating of such...

Inflammaging, the chronic subclinical systemic inflammation accompanying aging, represents a critical pathogenetic mechanism underlying age-related neurodegenerative diseases. While amyloid beta (Aβ) peptides are established contributors to neuroinflammation in Alzheimer's disease, their role in aging-related subclinical inflammation remains insufficiently elucidated. In humans, Aβ exhibits dual functions: it supports neuronal activity, survival, and protection against neurotrauma, while also...

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Nonhuman primates are widely used in preclinical biomedical research, with hematobiochemical values serving as key clinical pathology parameters for assessing health status. In this study, we collected and analyzed 2973 blood samples from 566 cynomolgus macaques and 193 rhesus macaques, along with anthropometric measurements such as BMI, body weight, and waist circumference. Corresponding human data were obtained from the NHANES database and incorporated into the study. Regarding white blood...