Aging & Longevity

CONCLUSION: This study shows for the first time age-related mitophagy impairment in human neurons, and confirms findings of age-related mitochondrial impairments in human neurons. By doing so, this study paves the way for more in-depth mechanistic studies that would allow for the identification of therapeutic targets for anti-aging treatment and in the context of age-associated neurodegenerative diseases.

Brain aging is associated with chronic, low-grade inflammation known as inflammaging, which is largely driven by senescent glial cells secreting pro-inflammatory factors termed as senescence-associated secretory phenotype (SASP). In humans, the release of SASP factors in the brain is linked with an increased risk for the development of neurodegenerative disorders; thus, elucidating the underlying molecular mechanisms is essential for understanding the pathophysiology of brain aging. Both NF-κB...

The decay of smooth muscle contractility is a major trigger of aging-related intestinal hypomotility, which imposes a substantial healthcare burden. Despite this, effective targeted therapy for this condition remains unavailable. Here, we identified the probiotic Bifidobacterium animalis subsp. lactis BL-99 as a microbiota modulator that restores gut motility through the bile acid (BA)-mediated rescue of smooth muscle contractile function. In a randomized, double-blind clinical trial...

Immune system changes with healthy aging lead to chronic systemic inflammation termed inflammaging, contributing to age-related pathologies. Alveolar macrophages (AMs) maintain lung homeostasis and health. The impact of inflammaging on AM populations requires further definition. Herein, we examined the effect of healthy old age on the phenotype and ontogeny of AMs from mice, non-human primates and humans. We identify three AM subpopulations in old age, including a CD11c^(+)CD11b^(+) population...

Early-life nutrition shapes lifelong health, yet the long-term consequences of childhood overnutrition, particularly on musculoskeletal aging, remain unclear. Here, we show that neonatal overfeeding acts as a developmental insult that accelerates age-related sarcopenia in both sexes. Using different mouse models, early overnutrition shortens lifespan and exacerbates late-life muscle atrophy, accompanied by metabolic dysfunction. Mechanistically, neonatal overfeeding disrupts goblet cell...

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The extent to which whole-blood NAD levels are altered in human disease or ageing remains controversial. Here we conducted 1,340 measurements in 1,068 adults, and found that whole-blood NAD levels do not decline with age in healthy individuals; they remain stable in males and increase in females, but are reduced in chronic diseases, specifically cardiovascular disease and hypertension. These findings indicate that whole-blood NAD levels track cardiovascular disease rather than chronological age....

Fibrous materials, ranging from connective tissues^(1-4) to engineered composites^(5-8), are vital to many biological and man-made systems, optimized to withstand complex in operando or in vivo loading. The load-bearing capacity of intervertebral discs (IVDs) of the spine depends on a hierarchical extracellular matrix, where plywood-like lamellae of collagen fibres in the annulus fibrosus contain nanometre-scale fibrils built from staggered triple-helical monomers^(4,9,10). How intact IVDs...

Perovskite/silicon tandem solar cells on rough textured substrates are at present limited by a critical trade-off in self-assembled monolayer (SAM) design because increasing molecular conjugation enhances conductivity but often leads to unfavourable aggregation that impairs conformal coverage^(1,2). Here we overcome this challenge using a rationally engineered molecular spatial conjugation that incorporates tailored intramolecular distortion to suppress excess π-π stacking without sacrificing...

Sarcopenia is a progressive age-related skeletal muscle disorder characterized by the decline of muscle mass and function, driven by mitochondrial dysfunction, oxidative stress, and chronic low-grade inflammation. Polyphenols have been proposed as candidate modulators of these pathways on mechanistic and preclinical grounds, but whether this plausibility translates into measurable structural and functional benefit in clinical trials remains unresolved. A systematic review following PRISMA 2020...

Motor lateralization, often expressed behaviorally as interlimb asymmetry, reflects distinct specializations of the dominant and nondominant motor systems. Although healthy aging has been associated with reduced motor lateralization, most previous studies have characterized this effect using coarse performance measures rather than specific motor-control processes. Here, we examined whether healthy aging alters the lateralization of gravity-related motor optimization, a motor-planning process...

Previous neuroimaging studies have demonstrated that beta-amyloid (Aβ) plaques and neurofibrillary tangles of tau are associated with disruptions in neurocognitive function in Alzheimer's disease. However, the relationship between Aβ, tau deposition, and functional network connectivity in normal aging and mild cognitive impairment remains unclear. Using resting-state functional MRI and Aβ PET and tau PET data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we applied multiple...

DNA methylation (DNAm) is a key epigenetic mechanism implicated in brain aging, yet methylation trajectories across the lifespan in the primate brain remain poorly understood. To characterize age-associated DNAm patterns in the hippocampus, we generated reduced representation bisulfite sequencing (RRBS) data from 86 rhesus macaque hippocampus samples spanning ~3-35 years of age (females = 56; males = 30). CpG-level analyses revealed minimal age-associated changes in mean methylation, with sites...

Aging is characterized by two interdependent hallmarks: a chronic low-grade inflammatory state known as inflammaging, and a progressive deterioration of sleep and circadian rhythms. Emerging evidence indicates that these are not merely parallel processes but are mechanistically intertwined in a self-perpetuating cycle. This review synthesizes current knowledge on how age-related sleep and circadian disturbances exacerbate inflammaging through distinct molecular and cellular pathways. We examine...

Declining global fertility has produced a growing, often invisible population facing Elderly Companionship Collapse-older adults who are childless, kinless, sole family survivors, or aging solo. AI companions already simulate presence; Phase II avatars that digitally resurrect deceased loved ones are now feasible. This prospect offers solace but risks a "perfection trap" that could incentivize replacing human partners, and ontological confusion by blurring the boundary between life and death. We...

Companion dogs are a valuable source of translational discovery about the basic biology of aging because of their well-characterized genome, phenotypic variation in lifespan, aging, and disease profiles, and diverse environmental exposures shared with their human owners. The Dog Aging Project (DAP)'s prospective, longitudinal open cohort study was begun in 2019 to investigate the biological and environmental determinants of healthy aging in companion dogs. As of December 31, 2024, the study has...

Age-related loss of muscle and bone mass and increased adiposity contribute to frailty, disability, falls, and fractures. The hallmarks of aging framework provide a biological model to investigate mechanisms underlying body composition remodeling. However, whether hallmark-related biomarkers are associated with longitudinal body composition changes remains unclear. We conducted a narrative review of longitudinal human studies examining associations between biomarkers and body composition...

CONCLUSIONS: In this cross-sectional study, lower cognitive performance in PD was more strongly associated with age at assessment and its interaction with disease severity than with age at onset. Education and cognitive reserve were positively associated with cognitive performance, consistent with their protective role.

Aging impairs organ regeneration, with insufficient angiogenesis as a key contributor. Here, we show that the endothelial immunoproteasome subunit PSMB8 is upregulated in aged mouse livers after partial hepatectomy. Endothelial PSMB8 deletion or PR-957 inhibition promotes angiogenesis and rescues liver regeneration. diGly proteomics identifies TAZ (transcriptional co-activator with PDZ-binding motif) as a ubiquitin-dependent immunoproteasome substrate, and TAZ activation restores aged liver...

Glaucoma, a leading cause of irreversible blindness, involves progressive retinal ganglion cell loss. Early detection of this neurodegeneration is critical, yet current clinical methods often identify disease only after substantial damage has occurred. This preliminary study used high-resolution adaptive optics-optical coherence tomography (AO-OCT) to track individual retinal ganglion cells in patients and healthy volunteers over 3 to 5 years. Results revealed higher neurodegeneration in...