Biogerontology最新文献

With the aging of the population, frailty has become a common syndrome that severely affects the quality of life of older adults. This study aims to analyze the correlation between cognition and frailty, physical activity and frailty, and elucidate the potential pharmacological targets of cognitive frailty and physical frailty.We conducted logistic regression analyses using data from the China Health and Retirement Longitudinal Study (CHARLS) to examine the associations between total cognition and frailty, physical activity and frailty. Furthermore, summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (TSMR) were employed to explore potential pharmacological targets for frailty. Genes associated with physical frailty and cognitive frailty were identified, followed by analysis via colocalization analysis, phenome-wide association studies (PheWAS), and DsigDB drug prediction. Cross-sectional analysis of CHARLs revealed that total cognition(OR 0.93, 95% CI 0.92-0.95) and middle physical activity(OR 0.95, 95% CI 0.92-0.97) were negatively correlated with frailty. SMR identified 41 drug genes associated with frailty, and subsequent TSMR validation and co-localization analysis showed that 11 candidate genes exhibited strong colocalization (PP.H4 > 0.8). GRPEL 1, PABPC 4, and WBP 2NL were ultimately identified as potential drug targets associated with physical frailty, while LANCL1, LRPPRC, FADS1, and WBP2NL were identified as potential drug targets associated with cognitive frailty. Phenome-wide association analysis(PheWAS) did not reveal any significant associations between these genes and other phenotypes at the genome-wide significance threshold. Laudanosine, 25-hydroxycholesterol, and hexadecanal emerged as the top three candidate compounds for therapeutic intervention. We identified potential drug targets for physical frailty and cognitive frailty through comprehensive analysis and elucidated drugs associated with potentially relevant genetic markers, thereby laying the foundation for a deeper understanding of the mechanisms of frailty.

Aging is a progressive and irreversible biological process that contributes to the pathogenesis of numerous age-related diseases. Elucidating the molecular mechanisms of aging is crucial for promoting healthy aging and extending healthspan. RNA-binding proteins (RBPs) are pivotal regulators of post-transcriptional gene expression and play essential roles in diverse biological processes. RBPs interact with both coding and non-coding RNAs to regulate RNA metabolism, stability, localization, and translation. Dysregulated RBP-RNA interactions have been closely associated with aging and age-related diseases. This review systematically summarizes the structural characteristics of RBPs and the evolution of methods used to study them. We focus on the molecular mechanisms of six key RBPs, namely HuR, AUF1, TTP, IGF2BP2, QKI, and LARP7, in the context of aging and age-related diseases. In addition, we discuss the regulatory functions of post-translational modifications of RBPs. Furthermore, we provide a multidimensional overview of RBP involvement in aging and age-related diseases through large language model (LLM)-based text-mining analysis. Our study provides a foundation for the comprehensive characterization of RBPs in aging and age-related diseases.

With the global rise in life expectancy, promoting healthy aging has become a central focus in biomedical research. From global initiatives like The World Health Organization's Decade of Healthy Ageing (2021-2030) to local ones, they highlight the need for accessible, non-invasive, and cost-effective tools to monitor aging-related physiological changes. Since the hand skin is an easily accessible tissue, it can offer valuable insights into aging processes, influenced by age, gender, and environment, as suggested by the paradigm of One Health. In this study, we exploited the potential of Visible and Near-Infrared Hyperspectral Reflectance Imaging (Vis-NIRHSI) as a quantitative, non-invasive method for monitoring skin aging in healthy individuals. A dataset of 101 hand-skin hypercubes images, from healthy volunteers over 40 years old, was acquired with a dedicated camera and analyzed in the range of 410 - 820 nm. A total of 224 spectral and texture features were extracted at selected wavelengths to investigate age-related variations in skin properties and to establish a standard reference map. Among these, 15 were retained as significant descriptors of the aging process and were used to build reference curves for the "healthy status condition." A questionnaire about quality and perception of lifestyle was administered to describe the sampled population in terms of exposome. Our findings suggest that hyperspectral skin analysis can serve as a promising biomonitoring approach for assessing aging dynamics and may contribute to the development of reliable tools for supporting healthy aging monitoring strategies.

Aging is the primary risk factor for neurodegenerative diseases, characterized by a progressive decline in cellular homeostasis. Central to this process is the mammalian target of rapamycin complex 1 (mTORC1), a convergent integrator regulator of metabolism that integrates nutrient sensing with cellular growth. While essential for development, chronic mTORC1 hyperactivity, termed mTORopathy, emerges during aging, driving a deleterious cycle of mitochondrial dysfunction, neuroinflammation, and impaired protein clearance. This pathological state promotes the accumulation of toxic proteins, such as amyloid-beta, tau, and alpha-synuclein, while simultaneously suppressing autophagy and glymphatic function. Furthermore, mTORC1 overactivation in glial cells fuels inflammaging by inducing cellular senescence and the senescence-associated secretory phenotype (SASP), which compromises blood-brain barrier integrity and synaptic plasticity. Conversely, pharmacological inhibition of mTORC1 using rapamycin or its analogs (rapalogs) has demonstrated significant neuroprotective potential. By restoring autophagic flux, rebalancing metabolic axes (AMPK/SIRT1), and suppressing chronic inflammation, these compounds can rescue synaptic function and reactivate neurogenesis. This review synthesizes current evidence regarding mTORC1 as a convergent integrator for brain aging and evaluates the clinical prospects of mTOR-targeted therapies in mitigating neurodegenerative decline.

Aging is accompanied by the accumulation of senescent cells and chronic low-grade inflammation, which together contribute to functional decline and tissue remodeling across organs. We previously reported that long-term nacre extract supplementation can delay age-related deterioration when initiated early; however, whether it can provide benefit under post-onset intervention conditions remains unclear. Here, we evaluated a water-soluble nacre extract derived from Pinctada fucata using (i) senescence-accelerated mouse prone 8 (SAMP8) mice and (ii) a D-galactose-induced aging paradigm, with treatment administered after the emergence of age-related phenotypes. In SAMP8 mice, nacre extract improved cognitive and neuromuscular performance, including Y-maze spontaneous alternation, novel object recognition, and forelimb grip strength, and showed a partial improvement in composite aging indices. These benefits were accompanied by reduced senescence-associated markers (p16, p21, and phosphorylated histone H2AX (γH2AX)) in skeletal muscle and peripheral organs, suppression of inflammation-associated signaling in skeletal muscle, and improved redox-related marker profiles. Nacre extract also increased satellite cell- and contractile marker-related immunoreactivity in aged skeletal muscle, suggesting improved regeneration- and maturation-related tissue characteristics. In the D-galactose model, nacre extract was introduced after impairments emerged and administered during the final 11 weeks of continued D-galactose exposure; under these post-onset intervention conditions, nacre extract improved grip strength, showed trends toward improved cognitive performance, and reduced senescence-associated markers in skeletal muscle and adipose tissue, supporting reproducibility across paradigms. Collectively, these findings indicate that nacre extract attenuates aging-associated functional and tissue alterations under post-onset intervention conditions by attenuating senescence- and inflammation-associated tissue responses and improving organism-level homeostasis.

Maternal sleep deprivation (MSD) is a common but usually unnoticed issue during pregnancy, and in recent years, it has been increasingly recognised as an important prenatal stressor that may adversely influence maternal physiology, placental function, and fetal neurodevelopment. Sleep disturbances during pregnancy, including reduced sleep duration, fragmented sleep, poor sleep quality, circadian disruption, and rapid eye movement sleep restriction, have been associated with altered hypothalamic-pituitary-adrenal axis activity, systemic inflammation, oxidative stress, and impaired circadian regulation. Emerging evidence from clinical and preclinical studies suggests that these alterations may affect fetal neurogenesis, synaptic development, neuroimmune signaling, and maturation of brain circuits involved in cognition and emotional regulations. Within the framework of the Developmental Origins of Health and Disease, maternal sleep disturbances may contribute to epigenetic modifications, mitochondrial dysfunction, microglial activation, and altered neuroplasticity-related pathways, which are increasingly implicated in long-term neurological vulnerability. Experimental findings further indicate that prenatal sleep disruption may impair offspring cognitive performance, emotional behavior, and stress responsiveness, while potentially influencing biological pathways associated with brain aging-related processes. However, the extent to which MSD directly contributes to pathological brain aging in humans remains incompletely understood. Factors such as timing and duration of exposure, sex-specific responses, and postnatal environmental conditions may further influence offspring outcomes. Therefore, this narrative review critically summarizes current evidence regarding MSD and examines the molecular, cellular, and neurodevelopmental mechanisms through which prenatal sleep disturbances may influence long-term neurological health and vulnerability to brain aging-associated alterations in offspring.This graphical abstract illustrates the mechanistic framework connecting maternal sleep deprivation to the developmental programming of brain aging in offspring. [ MSD: maternal sleep deprivation; DOHaD: Developmental Origins of Health and Disease; 11β HSD2: 11β hydroxysteroid dehydrogenase type 2; ROS: reactive oxygen species; REM: rapid eye movement; HPA axis: hypothalamic pituitary adrenal axis; BDNF: brain derived neurotrophic factor].

Kaempferol (KMP) is a dietary compound found in a wide range of foods. The therapeutic capabilities of these foods are associated with the phenolic compounds present in their structures, particularly their antioxidant activity. Remarkable medical care areas linked to KMP include pain relief, anti-aging, antiallergic, anticancer, antidiabetic, anti-inflammatory, antioxidant, antipyretic, central nervous system regulation, wound healing, and hepatoprotective characteristics. KMP has attracted considerable attention in the examination of its possible roles in dealing with a range of age-related diseases. These conditions include cardiovascular diseases (CVDs), immunoinflammatory diseases, neurodegenerative diseases (NDs), and cancer. It can delay oocyte aging, thereby enhancing the subsequent embryonic growth cascade. Delaying oocyte aging is mainly accomplished by reducing apoptosis and reactive oxygen species (ROS) levels. Furthermore, KMP has antioxidant effects on age-related diminished ovarian reserve (AR-DOR) by reducing HSP90 expression, thereby boosting NRF2 expression. KMP treatment influences multiple processes in aging oocytes, including peroxisome function, oxidative stress, cAMP signaling, TNF signaling, and gap junction pathways. Additionally, KMP improved negative pregnancy outcomes associated with fertilized aged oocytes.

This study aims to investigate the mechanism by which extract of Dendrobium officinale leaves (EDL) extends the lifespan of Caenorhabditis elegans. Untargeted metabolomics and network pharmacology analyses revealed that EDL primarily contains active components such as fatty acids, flavonoids, and polyphenols, which are predicted to potentially modulate pathways including MAPK, AMPK, mTOR, and longevity-related signaling pathways. Experimental results showed that 2 mg/mL EDL significantly extended the mean lifespan of nematodes by 11.4%, enhanced pharyngeal pumping rate and muscular endurance, but reduced brood size. EDL treatment also significantly decreased lipid droplet accumulation, cell apoptosis, and lipofuscin levels. Transcriptomic analysis indicated that EDL regulated the expression of multiple genes related to energy metabolism, particularly activating longevity-regulating pathways and the AMPK signaling pathway. RT-qPCR results demonstrated that EDL significantly increased the mRNA level of sod-3 in C.elegans. In conclusion, EDL may upregulate the expression of the sod-3 gene via the DAF-16/SOD-3 axis, thereby extending lifespan in C. elegans, providing a scientific basis for the high-value utilization of Dendrobium officinale leaves.

The ageing population and the increasing prevalence of age-related diseases underscore the urgent need for targeted therapeutic strategies. Accumulating evidence indicates that quinolinic acid (QA), a neuroinflammatory neurotoxin, contributes to the pathogenesis of neurodegenerative disorders. In this study, using Caenorhabditis elegans as a model organism, we demonstrate that chronic QA exposure acts as a robust driver of accelerated aging, significantly reducing overall healthspan. This pro-aging effect is accompanied by the premature onset of decreased locomotor function, enhanced lipofuscin accumulation, and decreased thermotolerance. Beyond these systemic aging phenotypes, QA induced pronounced cognitive deficits, including impaired short- and long-term associative memory and structural damage to dopaminergic neurons. Using this QA-induced injury model, we investigated the therapeutic potential of the clinical compound dimethyl fumarate (DMF), a derivative of a tricarboxylic acid cycle intermediate, and revealed that DMF's protective effects are partially dependent on the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In summary, our results demonstrate the therapeutic efficacy of DMF as a highly effective geroprotector and neuroprotector against QA-induced toxicity and define the Nrf2 pathway as a crucial mediator of the cognitive benefits of DMF, thus establishing its therapeutic repurposing potential for age-related neurodegenerative diseases.

Aging research has made remarkable progress in describing aging through the genetic architecture of longevity, epigenetic clocks, proteomic signatures, and systems-level analyses. Yet a critical dimension remains underrepresented: the role of genome integrity, germline and somatic mutation accumulation in individual-specific vulnerability, frailty, and multimorbidity across the life course. The need for individual-level thinking has deep roots, from Darwin's emphasis on individual variation in natural selection, to Garrod's chemical individuality, to Lewontin's genotype-phenotype (G-P) map and reaction norms. This tradition in evolutionary biology and medicine treats the individual as a primary unit of both selection and intervention. Here, we argue for an N-of-1 framework in aging research. Population-level epidemiology and genetics of aging based on means and variances can produce a "curse of the average," obscuring the individual genetic variation that impacts relative aging among individuals. The individual-centered N-of-1 framework would integrate longitudinal tracking of mutation accumulation ranging from individual cells, tissues, and organs into comprehensive individual aging profiles aligned with the G-P map concept. The emerging idea of "mosaic aging" further emphasizes that cells, cell types, tissues, organs, and organ systems within an individual reflect heterogeneous aging trajectories. We discuss how somatic mutations, operating through Muller's ratchet-like dynamics in stem cell populations, generate hierarchical vulnerabilities across biological scales. The extreme rarity of centenarians who may maintain superior genome integrity illustrates the relevance of this framework. We suggest that an integrated G-P map approach, grounded in evolutionary genetics, would advance both precision medicine and geroscience.