Biological age describes how a person is aging on molecular, cellular, and physiological levels. At the present time, biological age is not something that can be fully quantified and aging itself is far too complicated to be captured by a single layer of information. As such, it is relegated to being an abstract and somewhat vague idea. In this sense, biological age is remarkably similar to health. Health, like biological age, is not well defined and too multifarious to be summarized with a single biomarker. Given their similarities, it is intriguing to consider whether or not biological age and health are synonyms. Indeed, these two ideas can be cleanly swapped with each other in a variety of scenarios. If someone appears uniquely vigorous and capable for their chronological age, that person can be described as either quite healthy or being biologically youthful. However, there are situations where biological age and health diverge from each other. It is possible, for instance, to have a short healthspan but a long lifespan. While biological age is otherwise comparable to health as an abstract idea, it is possible that biological age and health will be confidently quantifiable in the future. Indeed, such quantification may be unlocked by the integration of multimodal data and artificial intelligence. In such a scenario, biological age offers a clear advantage over health in that it operates on a more intuitive, familiar scale as opposed to an artificially created index.

This study aims to investigate the relationship between serum levels of integrin alpha M (ITGAM), CX3CR1, and inducible nitric oxide synthase (iNOS) (microglial activation markers) and the development and severity of postoperative cognitive dysfunction (POCD) in elderly patients undergoing cardiopulmonary bypass (CPB). This observational study included 246 patients aged 60-80 years undergoing CPB. Serum levels of ITGAM, CX3CR1, and iNOS were measured preoperatively and early postoperatively (within 6 hours after surgery). Cognitive function was assessed preoperatively and 7 days postoperatively using the Montreal Cognitive Assessment and a comprehensive battery of neuropsychological tests. Receiver operating characteristic (ROC) analysis was employed to evaluate the predictive value of the biomarkers. Among the participants, 94 patients developed POCD, while 152 did not. Patients with POCD exhibited significantly higher early postoperative serum levels of ITGAM, CX3CR1, and iNOS compared to non-POCD patients. ROC analysis indicated moderate predictive accuracy for each biomarker individually (AUC: ITGAM = 0.78, CX3CR1 = 0.72, iNOS = 0.74), with a notable improvement when biomarkers were combined (AUC = 0.87). MoCA scores at 7 days postoperatively showed significant negative correlations with biomarker levels, while positive correlations were observed between biomarker levels and serum neuron-specific enolase, a marker of neuronal injury. Elevated postoperative serum levels of ITGAM, CX3CR1, and iNOS are strongly associated with the development and severity of POCD in elderly patients undergoing CPB. These biomarkers show promise as predictive tools for early identification of at-risk patients and may represent potential therapeutic targets for mitigating POCD by modulating microglial activation.

Chemotherapy remains a cornerstone in cancer treatment, yet its associated toxic effects, particularly pulmonary complications, pose significant clinical challenges. Chemotherapeutic agents, either alone or in combination, can induce severe pulmonary toxicity through mechanisms involving direct cytotoxicity, oxidative stress, and inflammatory responses. Drug-induced lung injuries, including interstitial pneumonitis, acute respiratory distress syndrome, and fibrosis, are commonly observed, with agents such as bleomycin, cyclophosphamide, and busulfan. Approximately 10% of patients undergoing chemotherapy experience pulmonary complications, necessitating effective management strategies. Emerging evidence suggests that natural products, particularly antioxidants and plant-derived compounds like ellagic acid, can mitigate chemotherapy-induced pulmonary toxicity by counteracting oxidative stress and inflammation. We aim to summarize the toxic implications of chemotherapeutic drugs on the respiratory system, elucidating the underlying pathophysiological mechanisms. It also explores potential therapeutic interventions, including natural products, to reduce pulmonary toxicity. A thorough understanding of overall mechanisms will aid in the advancement of targeted strategies to improve the efficacy of cancer treatment while minimizing adverse effects.

Mild cognitive impairment (MCI) lacks approved disease-modifying therapies. Classical multicomponent prescriptions may act on convergent neurobiological nodes. We combined network pharmacology with in vivo testing to evaluate Yizhi Dihuang Decoction (YZDHD). Constituents were curated from traditional chinese medicine systems pharmacology database and analysis platform (TCMSP) and high-throughput experiment- and reference-guided database of Traditional Chinese Medicine (HERB under blood-brain barrier-aware SwissADME criteria. Targets were inferred, intersected with MCI genes, organized into STRING and MCODE networks, and examined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Structure-based docking evaluated ligand-protein interactions across network-identified hub targets and ranked complexes by predicted binding energy. Predictions were tested in a D-galactose mouse model using the Morris water maze and novel object recognition, hippocampal histology with hematoxylin and eosin and Nissl staining, transmission electron microscopy, and molecular readouts by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), including PI3K, p-AKT/AKT, p-mTOR/mTOR, LC3-II/LC3-I, and p62/SQSTM1. We identified 152 bioavailable compounds and 381 overlapping targets that converged on hub kinases including AKT1, PIK3CA, PIK3CD, and mTOR; docking supported feasible engagement. In vivo, YZDHD improved spatial learning and recognition memory, preserved hippocampal cytoarchitecture and mitochondrial integrity, increased LC3-II/LC3-I, decreased p62/SQSTM1, and reduced activation indices of AKT and mTOR. YZDHD ameliorates MCI-like deficits by rebalancing PI3K-AKT-mTOR signaling and restoring autophagy-related activity. Signals for mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), epidermal growth factor receptor (EGFR), and toll-like receptor 4 (TLR4) broaden the mechanistic hypothesis space and warrant targeted follow-up.

Diminished ovarian reserve (DOR), affecting more than 10% of reproductive-aged women, leads to impaired fertility and systemic health disturbances. Baozhu Granule, a novel Chinese herbal formulation, has shown potential ovarian-protective effects in preliminary studies. This exploratory clinical trial aimed to investigate the efficacy and safety of Baozhu Granule in patients diagnosed with DOR. In this prospective, single-arm, open-label trial, 134 women aged 18-45 years with confirmed DOR were enrolled. Participants received Baozhu Granule (20 g, twice daily) orally for 12 consecutive weeks. The primary outcome was the recovery rate of ovarian reserve, assessed by antral follicle count and serum biomarkers. Secondary outcomes included menstrual recovery and changes in the Kupperman menopausal index (KMI). Evaluations were performed at baseline and after 12 weeks of treatment. Of the 134 enrolled patients, 108 completed the full treatment course; 20 of these were unable to attend the final visit (Visit 3) due to COVID-19 restrictions. Among the 88 patients evaluable at Visit 3, 68.2% showed recovery of ovarian reserve. Menstrual recovery was reported in 45.9% of patients, and 42.9% showed alleviation of menopausal symptoms (reduction in KMI). Subgroup analyses indicated that younger age, detectable anti-Müllerian hormone levels, and lower baseline follicle-stimulating hormone levels were associated with higher rates of ovarian reserve and menstrual recovery. Specifically, the overall recovery rate was 85.2% at 12 weeks of observation. No serious adverse events were reported throughout the study period. In this exploratory study, Baozhu Granule was associated with improvements in ovarian reserve, restoration of menstrual cyclicity, and relief of menopausal symptoms in women with DOR, with a favorable safety profile. These preliminary findings suggest its potential as a therapeutic option for DOR; however, further randomized controlled trials are needed to confirm these results.

Metformin use may be associated with reduced risk of all-cause mortality as well as prevent the onset of diseases of aging, namely cardiovascular diseases (CVD), cancer, and dementia. We systematically reviewed recent studies to determine whether metformin can promote healthspan in people with type 2 diabetes mellitus (T2DM). A comprehensive literature search was conducted using Medline, Embase, and Scopus for randomized controlled trials (RCTs) and cohort studies evaluating the effect of metformin on the incidence of all-cause mortality. Publications investigating metformin's effects on CVD, cancer or dementia were included. Search was restricted to English-only publications between 2016 and 2021. Full-text review, data extraction, and assessment of risk of bias using the Newcastle-Ottawa Scale were undertaken. Of 130 articles reviewed, 27 met the inclusion criteria. All 27 studies are observational cohorts, and no RCTs met the inclusion criteria, so causality cannot be inferred. No RCTs met the inclusion criteria. Five studies investigated the effects of metformin on all-cause mortality, 17 on the incidence of cancer, 3 on CVD, and 4 on dementia. Data heterogeneity precluded meta-analysis. Included studies were of high quality with NOS scores of 6-9. Metformin use in individuals with T2DM was associated with reduced risk of all-cause mortality, incidence of CVDs, and dementia. Metformin was associated with a reduced risk of prostate cancer but otherwise effects varied with cancer type and remain inconclusive.

Identification of natural compounds that delay aging and prevent age-related neurodegeneration is a key goal in gerontology. Fucoxanthin, a marine-derived xanthophyll, exhibits potent antioxidant properties, yet its effects on organismal aging and specific molecular mechanisms remain underexplored. Here, we investigated the pro-longevity and neuroprotective effects of fucoxanthin using Caenorhabditis elegans. Fucoxanthin supplementation significantly extended the mean lifespan of wild-type nematodes by 12.1% and improved health span, as evidenced by delayed age-related motility decline and enhanced resistance to oxidative stress. Notably, this lifespan extension occurred without compromising reproductive fitness. Genetic analysis revealed that the beneficial effects of fucoxanthin require the FOXO transcription factor DAF-16 and the autophagy-essential gene bec-1. Furthermore, fucoxanthin treatment increased autophagic flux and upregulated the expression of SKN-1/Nrf2-dependent detoxification genes, hsp-16.2 and gst-4. In nematode models of Alzheimer's and Parkinson's disease, fucoxanthin significantly ameliorated Aβ-induced paralysis and protected against dopaminergic neurodegeneration and α-synuclein accumulation in a DAF-16-dependent manner. Collectively, our findings demonstrate that fucoxanthin acts as a multitarget geroprotector that promotes healthy aging through the coordinated activation of DAF-16 and autophagy, suggesting its potential as a therapeutic intervention for age-related decline.

Huntington's disease (HD) is an inherited hyperkinetic movement disorder allied with chorea, cognitive impairment, and psychological disorders. Nerolidol (NRD) is a natural sesquiterpene alcohol obtained from many plants that has been shown to display neuroprotective properties. The current study focused on investigating the mechanism behind the neuroprotective role of NRD against 3-nitropropionic acid (3-NP)-induced neurotoxicity in experimental animals. Initial prediction was carried out through computational modeling (in silico), followed by a series of in vitro and in vivo experiments utilizing batteries of behavioral and molecular tests. Molecular docking was performed using Schrödinger (Maestro 2.0) to further explore NRD's neuroprotective capacity against 3-NP-induced neurotoxicity in SH-SY5Y cell lines and rats. For the in vivo study, 24 adult Wistar rats were randomly divided into four different groups, while NRD (50 and 100 mg/kg) was chosen to study their neuroprotective impact against HD-like symptoms utilizing different behavioral, biochemical, and histopathological parameters. In silico studies demonstrated that NRD has a high binding affinity for active sites of targeted enzymes, while in vitro data showed that NRD can counteract the neurotoxic effects of 3-NP in SH-SY5Y cells. NRD therapy (50 and 100 mg/kg) significantly improved motor activity, levels of malondialdehyde and glutathione, and histopathological changes. The findings revealed that NRD offers antioxidant and neuroprotective effects against 3-NP-induced neurotoxicity. The observed results indicated that NRD may exert its effects by activating the Nrf2 and heme oxygenase-1 pathways. Thus, it is suggested that it may be employed as an alternative treatment to fight against neurotoxicity.

Sarcopenia attenuates independence and mobility in older adults, and scalable nonpharmacological interventions are needed. This trial evaluated whether a 12-week exercise program improves activities of daily living, muscle mass and strength, physical performance, and systemic inflammation in older adults with sarcopenia. In this 12-week randomized controlled trial, adults aged 60-75 years with sarcopenia were randomized 1:1 to a control group or an exercise group. The exercise group performed postprandial multicomponent training (37 min/session, 3 days/week), combining resistance and aerobic exercise. Outcomes were measured at baseline and at week 12. The primary endpoint was the Modified Barthel Index (MBI). Secondary endpoints were Appendicular Skeletal Muscle Mass Index (ASMI), handgrip strength, the 6-minute walk test (6MWT), the Timed Up and Go Test (TUGT), and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Of 224 enrolled participants, 120 were randomized and 94 were analyzed (control, n = 49; exercise, n = 45). At week 12, the exercise group showed higher MBI (68.89 ± 9.60 vs. 62.02 ± 10.35; p = 0.001), ASMI (6.074 ± 0.904 vs. 5.295 ± 0.739 kg/m[2]; p < 0.001), and handgrip strength (22.78 ± 5.02 vs. 19.95 ± 4.25 kg; p = 0.009); better 6MWT (395.6 ± 55.6 vs. 363.7 ± 53.8 minutes; p = 0.005), shorter TUGT (6.76 ± 1.41 vs. 7.66 ± 1.55 seconds; p = 0.005), and lower IL-6 (45.21 ± 10.66 vs. 53.73 ± 10.99 pg/mL; p < 0.001) and TNF-α (38.09 ± 8.64 vs. 45.45 ± 8.07 pg/mL; p < 0.001) compared with the control group. These findings suggested that a 12-week regular exercise program improved functional independence, muscle health, mobility, and inflammatory status in older adults with sarcopenia.

To elucidate the mechanism of action of the Astragalus membranaceus-Panax ginseng herb pair in treating coronary heart disease (CHD) through network pharmacology combined with molecular docking and experimental validation. Active ingredients and target proteins were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. CHD-related targets were obtained from GeneCards and DrugBank. Overlapping targets were identified with a Venn diagram, and a protein-protein interaction network was built in STRING. Core targets were screened via topological analysis in Cytoscape 3.9.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed in Metascape. AutoDock Vina was used for molecular docking. In vitro, tumor necrosis factor (TNF)-α levels in HL-1 cells subjected to oxygen-glucose deprivation (OGD) were measured by ELISA, and the effect of mangiferin pretreatment on cell viability was assessed with a CCK-8 assay. Forty-one active ingredients and 207 putative targets were identified for the herbal pair, and 1843 CHD-related targets were collected; 67 overlapping therapeutic targets were obtained. Topological analysis yielded 27 core targets. GO terms were enriched in responses to lipopolysaccharide, toxic substances, and organic cyclic compounds; molecular functions included cytokine-receptor binding and transcription-factor binding; and cellular components were mainly membrane rafts and extracellular matrix. KEGG analysis highlighted the TNF, fluid-shear-stress, and NF-κB signaling pathways. Docking showed strong binding between key components and targets. In vitro experiments demonstrated that formononetin pretreatment significantly reduced OGD-induced TNF-α levels and improved HL-1 cell viability. The A. membranaceus-P. ginseng combination herb pair exerts anti-CHD effects via multiple bioactive ingredients (e.g., formononetin, quercetin, isorhamnetin, ginsenoside Rh2, kaempferol) by targeting TNF, AKT1, PTGS2, and JUN and modulating pathways including the TNF and NF-κB signaling pathways.

Salvia miltiorrhiza (SM)-Dalbergia odorifera (DO) is a commonly used circulating blood and transforming stasis drug pair for the treatment of cardiovascular and cerebrovascular diseases, but systematic studies on the optimal ratio for the treatment of cerebrovascular diseases have not been reported. In this study, we determined the optimal ratio of SM-DO for the treatment of ischemic stroke (IS) through the mixture design.Five different ratios of SM and DO were applied to middle cerebral artery occlusion (MCAO) mice using an enhanced simplex center-of-mass mixture design by Minitab 17 software. The experimental ratios of SM and DO as independent variables and dependent variables including modified neurological severity scores, corner test, sticker removal test, cylinder test, 2,3,5-triphenyltetrazolium chloride staining, lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) levels, and the optimal ratio of the two herbs was obtained by fitting regression equations through mixture design and multi-objective synchronization optimization. The therapeutic effects of the optimal ratio of SM-DO on MCAO mice were verified and evaluated by the indicators of neurological function, brain swelling, cerebral infarction volume, brain histopathological morphology, and the levels of LDH and NSE. The optimal ratio of SM:DO = 0.61:0.39 was obtained by multi-objective synchronization optimization. The results of pharmacodynamic validation showed that the optimal ratio of SM-DO significantly improved the neurological function scores of MCAO mice, the motor functions of the left forelimb, the sensory functions of the left paw, the motor functions of the right steering, the cerebral infarct volume, and the release of LDH and NSE and exerted the therapeutic effect on IS. The optimal ratio of SM (0.61) and DO (0.39) was found to be effective in the treatment of IS mice based on mixture design.

Alzheimer's disease (AD) is an aging-associated neurodegenerative disorder characterized by amyloid-β (Aβ) and tau accumulation and progressive cognitive decline. Increasing evidence implicates the glymphatic system, a brain-wide perivascular pathway involved in cerebrospinal fluid-interstitial fluid exchange and metabolic waste clearance, in the removal of Aβ, tau, and other solutes relevant to AD pathogenesis. Aging-related alterations in aquaporin-4 polarization, arterial pulsatility, sleep architecture, and cerebrovascular integrity may impair glymphatic transport and thereby promote protein retention and neurodegeneration. In this review, we summarize current knowledge of glymphatic anatomy and function and discuss its implications for AD, with particular emphasis on modifiable factors such as sleep, exercise, vascular health, and aging-associated decline. We further highlight emerging therapeutic and potential intervention strategies aimed at restoring glymphatic function, and critically evaluate current methods for assessing this system in humans together with the evidence obtained to date. Although human studies increasingly support the relevance of perivascular fluid transport to AD-related pathology and cognitive outcomes, mechanistic insights remain largely derived from animal models, and human assessment is still constrained by methodological and imaging limitations. Overall, the glymphatic system provides a useful framework for linking brain aging to impaired clearance in AD. Further refinement of human biomarkers and longitudinal translational studies will be essential for clarifying their clinical relevance and therapeutic potential.

Agrin-mediated neuromuscular junction (NMJ) morphological alterations is one of the main pathogeneses of sarcopenia. The aim of this study was to observe the changes in serum agrin in patients with different degrees of sarcopenia and the alterations in Agrin receptors in human skeletal muscle with age. A total of 236 elderly subjects were enrolled and categorized into nonsarcopenia, possible sarcopenia, sarcopenia, and severe sarcopenia groups. Serum levels of the C-terminal Agrin fragment were quantified using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. In addition, in a distinct and smaller exploratory subgroup (n = 12), quantitative real-time polymerase chain reaction and immunofluorescence staining were performed to investigate the expression of Agrin receptors, specifically low-density lipoprotein receptor-related protein 4 (Lrp4) and alpha-dystroglycan (α-DG), in human skeletal muscle samples. Compared with that in the nonsarcopenia group, the level of agrin in the other groups was significantly different. Partial correlation analysis and binary logistic regression analysis suggested that the level of Agrin was associated with handgrip strength. There was a significant increase in the serum level of agrin and a reduction in the mRNA expression of the agrin receptors Lrp4, α-DG, and RAPSN, while immunofluorescence analysis confirmed the expression patterns of the Lrp4 and α-DG receptors. In the elderly population, the level of agrin decreased in patients with sarcopenia, while the expression of its receptors also decreased. These factors result in NMJ morphological alterations, weakened muscle contraction, and increased risk of sarcopenia.

To investigate the protective effects of Nvshi Oral Liquid on skin aging and oxidative stress in 4-vinylcyclohexene diepoxide (VCD)-induced menopausal rats and Ultraviolet B (UVB)-irradiated HaCaT cells. VCD-induced menopausal rats and UVB-damaged HaCaT cells under low-estrogen conditions were established. Nvshi Oral Liquid was administered at low (2%), medium (6%), and high (10%) concentrations. Cell viability, Reactive Oxygen Species (ROS) levels, antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase), inflammatory cytokines [Interleukin-1 beta, Interleukin-6, Tumor Necrosis Factor-alpha (IL-1β, IL-6, TNF-α)], and the expression of aquaporin-3 (AQP-3), complement component 1q binding protein (C1QBP), and keratin 19 (K19) were assessed using Cell Counting Kit-8 (CCK-8) assay, fluorescence staining, enzyme-linked immunosorbent assay, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR), and Western blot. Nvshi Oral Liquid significantly improved HaCaT cell viability, reduced ROS levels, enhanced antioxidant enzyme activities (SOD increased by 1.8-fold, p < 0.01), and suppressed inflammatory cytokines. Both mRNA and protein expression levels of AQP-3, C1QBP, and K19 were consistently increased in rat skin tissues and HaCaT cells. Histological analysis further demonstrated improved skin structure. Nvshi Oral Liquid attenuates menopausal skin aging by enhancing antioxidant capacity and restoring skin barrier function, which is associated with regulation of AQP-3, C1QBP, and K19 expression. These findings suggest a potential natural intervention for menopausal skin health.