Frontiers in aging最新文献

The human gut microbiota is comprised predominantly of bacteria, and also includes archaea, fungi, and viruses. The gastrointestinal epithelium, mucosal barrier, and mucosal immune system balance protection against infection at mucosal entry points with symbiosis and tolerance to non-harmful organisms and antigens. Aging is associated with notable changes in both gut microbiota and mucosal immunity, including reduced microbial diversity, increased proportion of pathobionts relative to commensals, immunosenescence, and chronic inflammation. These changes may disrupt gastrointestinal function and homeostasis and increase susceptibility to infection and inflammatory conditions. Multiple drug classes are also associated with disruption of the gut microbiota and mucosal immunity, including antibacterials, proton pump inhibitors (PPIs), metformin, and steroidal and non-steroidal anti-inflammatory agents. This review describes the mechanisms by which these drugs affect the gut microbiota and mucosal immunity to provide perspective of the concurrent effects of drugs and age-related changes.

Background: Older adults are at high risk for traumatic brain injury (TBI), yet there is limited evidence on their vulnerability to mortality, morbidity, and associated risk factors in low-and-middle-income countries. This study assessed the burden, health outcomes, and health-seeking behavior of TBI in older adults at the largest teaching hospital in Bangladesh.

Methods: The study analyzed data from individuals aged 60+ years who were part of a prospective observational cohort of TBI patients admitted to a teaching hospital in Dhaka, Bangladesh, from May to June 2017. Data were collected at admission and during discharge or a 30-day follow-up (whichever came earlier) using a pre-tested semi-structured questionnaire, including the Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), and EuroQol-5D-3L. Descriptive analyses assessed the burden, characteristics, and health-seeking behavior for TBI, while relative risks were calculated to evaluate the risk of mortality by socio-demographic characteristics and clinical status.

Results: During the study period, 117 older TBI patients were admitted, with 78.6% being male. Road traffic injuries (RTI) accounted for 71.3% of cases, followed by falls (16%). Half of the patients did not receive treatment at the primary and secondary facilities they initially visited, and 16% experienced over 24 h' delay in treatment initiation. On admission, 25% presented with severe injury (GCS ≤8), and all had a history of loss of consciousness. The mortality rate was 5.2 per 1,000 person-days. Severe mobility issues and anxiety/depression were reported by 11% during follow-up. Bivariate analysis indicated higher mortality risk in patients with low socio-economic status, GCS ≤8, and over 1-h duration of both loss of consciousness and post-traumatic amnesia.

Conclusion: RTI and falls are major causes of TBI, disproportionately affecting older adults of lower socio-economic status. Treatment accessibility gaps exist, and clinical status at admission is critical for predicting mortality. Findings can inform policies for preventive and rehabilitative strategies, including priority management protocols for older TBI patients in Bangladesh.

Geranylgeranoic acid (GGA) is a naturally occurring acyclic isoprenoid with chemopreventive effects against hepatocellular carcinoma. In mammals, GGA is endogenously synthesized via the oxidative metabolism of geranylgeraniol by monoamine oxidase B (MAOB). However, MAOB activity decreases with age, leading to reduced hepatic GGA levels. Emerging evidence suggests that cytochrome P450 3A4 (CYP3A4) may compensate for this decline, providing an alternative oxidative pathway in MAOB-deficient conditions. This mini-review summarizes the current findings on GGA biosynthesis and metabolism in the aging liver, focusing on the MAOB-CYP3A4 axis, in which MAOB serves as the primary enzyme for endogenous GGA synthesis and CYP3A4 provides a compensatory pathway under MAOB-deficient conditions, and its relevance to age-related hepatic dysfunction. By discussing recent evidence on enzymatic compensation and age-dependent metabolic changes, this review highlights how the CYP3A4-GGA pathway may help unravel the complexity of hepatic aging. These findings may provide a mechanistic basis for developing preventive strategies targeting age-related hepatocarcinogenesis, particularly in older individuals with reduced MAOB-GGA activity.

At present, there are no approved drugs for the treatment of aging, but a number of studies have reported related anti-aging drugs. As an innovative traditional Chinese medicine (TCM) that has been on the market for many years to treat waist and knees soreness, dizziness, tinnitus, fatigue, and cold limbs caused by insufficient kidney-yang, "Bazi Bushen Capsules (BZBS)" has also made a series of new and remarkable achievements in anti-aging research, which is expected to become the first new drug approved by the National Medical Products Administration (NMPA) for anti-aging indications, thus opening up new ideas for the medical field to treat aging. In the context of anti-aging, the general social phenomenon expected to be effectively caused is that people will enter a new era of longevity, and most countries will move from the current aging society to the aged society and even into the super-aging society in the near future. This remark provides forward-looking and guiding suggestions for future research on the relationship between longevity, economy and social protection.

Kefir, fermented milk rich in probiotics, has attracted growing attention for its potential anti-aging effects. Yet, studies specifically addressing kefir in the context of aging remain limited and scattered across diverse biological fields. To overcome this fragmentation, we applied an integrative approach that combines a cutting-edge AI-assisted algorithm for evidence screening with a Python-based semantic clustering pipeline. This allowed us to systematically map and classify the existing literature into four functional domains of aging: changes in body composition, energy balance, homeostatic signaling networks, and neurodegeneration. The resulting evidence map revealed a marked thematic imbalance, with most studies concentrated in mechanistic pathways such as inflammation and oxidative stress, and far fewer addressing neurocognitive or metabolic outcomes. This asymmetry suggests a structural bias in current research priorities and highlights the need to expand kefir-related studies toward more clinically relevant aging endpoints. By merging AI with domain-specific linguistic tools, our study provides a reproducible and data-driven strategy to uncover thematic blind spots and guide future investigations into kefir's anti-aging potential.

Natural autoantibodies (NAbs) are a key component of the immune system, produced mainly by B-1 cells without prior antigenic stimulation. These antibodies exhibit broad reactivity toward both self and non-self antigens and contribute to immune homeostasis by clearing apoptotic cells and cellular debris, modulating immune responses, preventing autoimmune reactions, and promoting tissue repair. NAbs are present in intravenous immunoglobulin (IVIg) preparations, where they play an important role in the therapeutic effects observed in autoimmune, inflammatory, and neurodegenerative diseases. Importantly, NAbs of the IgG class contained in commercial IVIg originate from large-scale pooling of sera from thousands of healthy donors, and are recovered after multiple enrichment and purification steps during the manufacturing process. This review provides a comprehensive overview of the physiological functions of NAbs and their involvement in the mechanisms of action of IVIg. The review particularly focuses on anti-idiotypic antibodies within IVIg, which can neutralize pathogenic autoantibodies in diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and pemphigus vulgaris. In the neurological field, NAbs in IVIg have been shown to target misfolded proteins such as amyloid-beta and alpha-synuclein, reduce neuroinflammation, and support neuronal survival, with promising results in Alzheimer's disease, Parkinson's disease, autoimmune encephalitis, and small fiber neuropathy. Similarly, in dermatological and systemic autoimmune diseases, NAbs contribute to immune regulation and the neutralization of tissue-damaging autoantibodies. Enhancing the therapeutic potential of IVIg through selective enrichment of beneficial NAb subsets could represent a promising direction for future research aimed at improving outcomes in a wide range of immune-mediated diseases.

Autoimmune diseases, particularly those with early onset such as systemic lupus erythematosus, juvenile idiopathic arthritis, and type 1 diabetes, are paradoxically characterized by molecular and cellular features typically associated with aging. These include telomere shortening, mitochondrial dysfunction, epigenetic alterations, and skewed immune cell phenotypes, which are considered hallmarks of immunosenescence. This perspective explores the hypothesis that aberrant inflammasome activation, particularly of the NLRP3 complex, serves as a key upstream driver of premature immune aging in autoimmunity. We examine how chronic inflammasome signaling induces senescence through pro-inflammatory cytokine production and oxidative stress, reinforces the senescence-associated secretory phenotype (SASP), and perpetuates immune dysregulation. By reframing autoimmunity as a disorder of accelerated immune aging, we highlight emerging opportunities for therapeutic intervention using senolytics, inflammasome inhibitors, and lifestyle modifications. In addition, incorporating biomarkers of immune aging into clinical assessment may enable precision immunogerontology, particularly in pediatric populations where biological and chronological age may be dissociated. Elucidating the relationship between inflammasome signaling and immune senescence provides a critical framework for understanding autoimmune pathogenesis and for developing interventions that modify disease course by targeting age-associated mechanisms.

The nucleosome remodeling and deacetylase (NuRD) complex, well known for its ATP-dependent chromatin remodeling and histone deacetylation activities combined in one multi-subunit complex, plays an evolutionarily conserved role in chromatin structures and gene regulation during cell growth, proliferation, and development. However, the composition and function of the NuRD complex in planarians remain incompletely unknown. Here, we identified six core components within the NuRD complex and characterized their biological roles in planarians. RNA interference (RNAi) mediated knockdown of these genes resulted in similar perturbations to both tissue homeostasis and regeneration, and the overlapping downstream genes regulated upon depletion of MBD2/3 or CHD4 showed similar expression alterations to that after knockdown of other NuRD complex genes, suggesting that NuRD core members may act in one complex. Additionally, the overlapping upregulated genes after depletion of NuRD complex members were expressed in neoblast and progenitor cells, among which NuRD complex core genes were enriched, suggesting transcriptional correlation between the overlapping upregulated genes and NuRD core members. Furthermore, upstream regulatory sites of the upregulated genes exhibited significant enrichment of H3K27ac, indicating the NuRD complex may deacetylate histone to modulate these genes. Notably, depletion of either MBD2/3 or CHD4 in planarians significantly upregulated multiple progenitor marker genes while reducing the number of somatic cells in the epidermis and intestine and downregulating multiple somatic cell marker genes, indicating that the NuRD complex may drive differentiation into somatic lineages in planarians. Collectively, our work provides a foundation to understand the essential roles of the NuRD complex in orchestrating cell differentiation, tissue homeostasis and regeneration in planarian.

Background: Ageing trajectories for foreign-born individuals and women living with HIV remain poorly defined globally. This study aimed to characterize foreign-born women living with HIV aged ≥65 years (FWLH) and compare them to age-matched Italian women (IWLH) and foreign-born men living with HIV (FMLH).

Methods: Data were drawn from the multicenter Italian geriatric HIV cohort (GEPPO). We described sociodemographic characteristics, viro-immunological status, comorbidities, and multidimensional geriatric assessment in FWLH. A complete case analysis was supplemented by multiple imputation using the mice package with the Predictive Mean Matching (PMM) method, and pooled estimates were derived from regression models, that included an interaction term for sex × birthplace.

Results: We included 330 participants: 285 (86.5%) women, 15 (4.5%) FWLH and 30 (9%) FMLH. Comparing FWLH to IWLH, lower CD4+/CD8+ ratio (beta -0.38; 95% confidence interval (CI) -0.79, 0.03; p-value = 0.069) and percentage of CD4⁺ cell (beta -10; 95% CI -16, -4.1; p-value = 0.001) and higher weight (beta 11; 95% CI 3.4, 18; p-value = 0.004) and BMI (beta 3.8; 95% CI 0.57, 7.0; p-value = 0.021) were observed. Comparing FMLH to FWLH, we found lower prevalence of multimorbidity (IRR 0.60, 95% CI 0.37, 0.98, p-value = 0.039) and osteoporosis, though risk difference for osteoporosis was not significant. In the interaction model, FWLH had a lower percentage of CD4⁺ cells (β = -0.38; 95% CI: -0.73, -0.02; p = 0.036).

Conclusion: FWLH in a geriatric cohort showed a profile of immune imbalance and higher weight, BMI, and multimorbidity; this may be possibly related to a worse metabolic profile and poorer access to care. However, there was no difference in virological response and antiretroviral therapies. Enhancing our understanding of older FWLH is crucial for promoting person-centered care a patient-centred care and healthy ageing in this population.