npj aging最新文献

As individuals age, cortical alterations in brain structure contribute to cognitive decline. However, the specific patterns of age-related changes and their impact on cognition remain poorly understood. This study assessed the effects of aging on individual gray matter similarity networks and compared them to anatomical and functional connectivity networks derived from diffusion-weighted imaging and resting-state fMRI, respectively. Our results showed that gray matter similarity networks outperformed anatomical and functional connectivity in predicting age and cognition, showing the earliest age-related changes across the adult lifespan. These networks also demonstrated greater robustness to individual differences in cognition, behavior, and sex. Notably, age-related changes in gray matter similarity were associated with the brain's underlying cytoarchitecture, being strongest in brain regions from cortical layers II and III. These findings provide a new biological insight into the neural mechanisms of cognitive aging and highlight the potential of individual morphological similarity for capturing complex brain changes across the lifespan.

Aging is accompanied by low-grade intestinal inflammation, shifts in gut microbiota, and impaired oxidative balance. Probiotic supplementation has been proposed to mitigate these processes, yet evidence in elderly populations remains limited. In this pilot trial, older adults received oral Lactiplantibacillus plantarum OL3246 or placebo, with assessments including fecal calprotectin and zonulin as markers of intestinal inflammation, systemic oxidative stress parameters, self-reported quality of life and mood, and gut microbiome composition analyzed by sequencing and functional profiling. L. plantarum OL3246 supplementation was well tolerated and associated with consistent improvements across clinical, biochemical, and microbial measures. Participants reported enhanced quality of life and mood, while fecal calprotectin levels declined, indicating reduced intestinal inflammation. Moreover, oxidative stress markers improved with lower AOPP, stabilization of SOD, and restoration of redox balance. Microbiome analyses showed greater diversity and enrichment of health-associated taxa. These findings indicate that Lactiplantibacillus plantarum OL3246 may support healthy aging.

Little is known about tissue-specific changes that occur with aging in humans. Using the description of 33 million histological samples we extract thousands of age- and mortality-associated features from text narratives that we call The Human Pathome (pathoage.com). Notably, we can broadly determine when post-development aging starts at the organism and tissue level, indicating a sexual dimorphism with females aging earlier but slower and males aging later but faster. We employ unsupervised topic-modeling to identify terms and themes that predict age and mortality. As a proof of principle, we cross-reference these terms in PubMed to identify nintedanib as a potential aging intervention and show that nintedanib reduces markers of cellular senescence, reduces pro-fibrotic gene pathways in senescent cells and extends the lifespan of fruit flies. Our findings pave the way for expanded exploitation of population text datasets towards discovery of novel aging interventions.

Hypertension prevalence is increasing in both aging and younger populations, with high salt intake being a key environmental driver. Whether young and aged individuals exhibit similar physiological and molecular responses to salt loading remains unclear. This study compared hemodynamic and renal redox adaptations to salt loading in young (8-week) and aged (50-week) Dahl salt-sensitive (DSS) rats. Both groups developed salt-sensitive hypertension, but blood pressure (BP) elevation was markedly lower in aged rats. High salt induced marked increases in stroke volume (SV), cardiac output (CO), and vascular indices, indicating strong cardiac and vascular contributions to BP rise. In contrast, aged rats displayed blunted increases in SV and CO, together with attenuated changes in vascular indices, reflecting diminished cardiac contractility and vascular responsiveness that accounted for their lower BP salt sensitivity. High salt disrupted redox homeostasis in both groups, but aged rats exhibited inherently reduced antioxidant capacity and greater renal oxidative stress, along with more pronounced glomerulosclerosis and interstitial fibrosis. Nitric oxide pathway suppression was more evident in young rats, whereas aged rats showed persistently low baseline NO availability. These findings demonstrate that aging reduces hemodynamic and vascular responsiveness to salt loading yet heightens susceptibility to salt-induced renal injury in DSS rats.

Parkin, a mitochondrial E3 ubiquitin ligase, plays a central role in mitophagy and cellular homeostasis. Although well studied in neurobiology, its role in female reproduction remains unclear. This study investigated the role of Parkin on female fertility using young (2-3 months old) and older (9-10 months old) mice with a global germline Parkin deletion. Parkin knockout (KO) females exhibited significantly reduced fertility with total pups per female lower in KO mice (16.0 ± 1.53) compared to wild type (WT) (22.33 ± 0.67; p = 0.02). In young mice, GV oocyte yield was significantly reduced in KO (30.0 ± 1.53) compared to WT (52.7 ± 6.96; p = 0.03), as was MII oocyte count (7.7 ± 0.67 vs. 22.3 ± 0.88; p = 0.0002). In older mice, similar trends were observed. Fertilization rates were significantly lower in KO mice compared to WT (36.2 ± 8.1% vs. 61.2 ± 5.5%; p = 0.03). RNA sequencing identified multiple differentially expressed genes between KO and WT, with associated pathway changes. These findings indicate that Parkin deficiency impairs oocyte yield, fertilization capacity, and overall fertility, suggesting that Parkin plays a key role in reproductive competence.

Age-related deterioration of the sensorimotor system can impair proprioception. This study aimed to characterize age-related changes in the sense of position and movement. Three experiments involved two groups of participants (29 young adults and 26 older adults) to i) evaluate the performance in a position matching task (Experiment 1), ii) assess the perception and reproduction of an illusory movement evoked by proprioceptive stimulation (mechanical muscle-tendon vibration) (Experiment 2), and iii) investigate the ability to discriminate between illusory movements evoked with different frequencies of stimulation (Experiment 3)). No significant differences were found between young and older in the position matching task performance in Experiment 1. In contrast, in Experiment 2, older adults manifested a hyper-illusory experience of movement eliciting perception of wider and faster movements than young. Furthermore, psychometric analysis indicated a reduced ability in older adults to discriminate among different illusory experiences. This study provides the first evidence that aging is associated with an increase in illusory experiences in the elderly, a phenomenon likely related to changes in the mechanisms that control the responses of the Ia muscle spindles fibers and the central processing of the afferent signals.

Aging is characterized by progressive physiological decline and increased vulnerability to metabolic and inflammatory disturbances. Palmijihwang-hwan (PM), a traditional East Asian herbal formula, has been used empirically for age-related complaints, but its mechanistic basis remains unclear. Here, we evaluated the effects of early-onset PM administration (starting at 2 months of age) on longevity-related phenotypes and metabolic regulation. PM significantly prolonged lifespan in Caenorhabditis elegans and improved survival in ICR mice without evident toxicity. Preventive PM administration reduced epididymal white adipose tissue (eWAT) mass and circulating insulin/adipokine levels. Lipidomic analysis showed a shift from lysophospholipids toward phospholipids, accompanied by downregulation of PLA2G7, indicating attenuation of adipose inflammation. PM also reshaped the gut microbiota, decreasing inflammation-associated taxa such as Oscillibacter valericigenes, and lowered adipose IL-6 and TNF-α expression. Collectively, these findings indicate that preventive early-onset PM administration modulates the gut microbial composition, counteracting the age-related enrichment of inflammation-related bacteria.

Skin aging involves progressive structural and functional decline, yet the underlying molecular mechanisms remain unclear. Here, we report that the antimicrobial peptide S100A7 is markedly reduced in aged keratinocytes and that its depletion leads to transcriptional alterations in differentiation-, autophagy-, and senescence-associated pathways. S100A7 knockdown partially recapitulated senescence-associated signatures, whereas supplementation increased autophagy and attenuated senescence-like phenotypes. These findings support a role for S100A7 as a context-dependent modulator of epidermal homeostasis and establish an AMP-autophagy axis that may contribute to cellular changes during skin aging.

Evidence suggests that cancer-related accelerated aging contributes to an earlier onset of chronic diseases; persistent symptoms; and decrements in patients' quality of life. This review presents the Multifactorial Model of Cancer-related Accelerated Aging (MMCRAA), a conceptual framework that is grounded in Life Course Theory and supported by empiric evidence. The model includes six inter-related concepts: person, behavioral, biological, treatment, symptom, and life course factors. The MMCRAA can be used by clinicians and researchers to identify patients at increased risk for cancer-related accelerated aging; guide personalized treatment planning; and inform the development of interventions and research.