BMB Reports最新文献

Aging represents a fundamental evolutionary feature shared across all living organisms, intrinsically coupled with development and lifespan. It is orchestrated by a complex polygenic architecture involving numerous small-effect variants distributed across diverse biological pathways, giving rise to striking interindividual variation in aging trajectories and lifespan. Over the past decade and a half, genome-wide association studies (GWAS) have uncovered multiple loci associated with lifespan, healthspan, exceptional longevity, and aging, converging on key biological processes such as lipid metabolism, inflammation, insulin/IGF signaling, and DNA repair. These discoveries have illuminated conserved molecular networks underlying the regulation of aging and longevity. Nevertheless, the identified variants collectively account for only a modest fraction of heritability, underscoring that aging and longevity arise from the cumulative and coordinated actions of myriad common alleles within complex biological networks. In this minireview, we synthesize major genetic insights from GWAS of aging and longevity, delineate recurrent pathways and molecular themes, and discuss how these findings refine our understanding of the genomic foundations of lifespan variation. We further highlight outstanding challenges, including phenotypic heterogeneity, ancestry-specific effects, and the limited predictive power of current models, and propose conceptual directions for future research aimed at establishing a more comprehensive and mechanistic framework for the genetic architecture of human aging and healthy longevity. [BMB Reports 2026; 59(1): 2-12].

Aging poses one of the most urgent biomedical challenges of the 21st century, increasing vulnerability to chronic diseases and limiting healthspan in aging populations. Recent advances in aging research are transforming our understanding of aging from an inevitable decline to a multidimensional and potentially modifiable biological process. This special issue presents five invited reviews that collectively illustrate the recent progress in aging research. These articles introduce emerging concepts that shed light on the fundamental causes of aging, including the genetic architecture underlying human aging, senescence-driven fibrotic scarring arising from imperfect tissue repair, and the progressive erosion of epigenetic information in the brain. They further highlight promising avenues for intervention-such as epigenetic rejuvenation, the bidirectional interplay between the aging gut microbiome and host physiology, and the emergence of precision geronutrition. By integrating genetic, molecular, cellular, microbial, and nutritional perspectives, this collection emphasizes a future where extending human healthspan is both realistic and scientifically attainable. [BMB Reports 2026; 59(1): 1-1].

The gut microbiota plays a fundamental role in maintaining host homeostasis, and the aging process profoundly influences its composition and function. Accumulating evidence suggests that alterations in the gut microbiota are not just a consequence of aging, but also an active driver of age-related physiological decline. In particular, age-dependent gut microbiota dysbiosis has emerged as a critical factor contributing to host aging and aging-related diseases. This review systematically summarizes alterations in the gut microbiota (e.g., reduced alpha diversity, depletion of beneficial commensals, and enrichment of pathobionts) during the aging process, and discusses the spatiotemporal dynamics and causal relationships between microbial aging and host aging. The regulatory mechanisms by which the gut microbiota influences aging-related diseases, such as metabolic disorders (e.g., obesity, type 2 diabetes, and cardiovascular disease), immunosenescence, and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), are also elucidated. Finally, microbiota-targeted intervention strategies (e.g., probiotics, prebiotics, and postbiotics) are explored, together with advanced research strategies. [BMB Reports 2026; 59(1): 40-50].

Altered nuclear morphology, one of the characteristics of cancer cells, is often indicative of tumor prognosis. While reactive oxygen species (ROS) are known to induce nuclear morphology changes, mechanisms underlying these effects remain elusive, particularly regarding nuclear assembly. We hypothesized that mitotic cells might exhibit increased susceptibility to ROSinduced nuclear deformation due to the dynamic nature of nuclear envelope during mitosis, i.e., disassembly and reassembly. Interestingly, we discovered that exposure of mitotic cells to hydrogen peroxide (H2O2) resulted in persistence of lamin aggregates during early mitosis, which coincided with aberrant nuclear morphology. Further investigation revealed a dampening effect of H2O2 on Cdk1, a pivotal kinase governing mitotic entry. Our in vitro kinase assays demonstrated that H2O2 mediated reduction of Cdk1 activity, resulting in diminished phosphorylation of lamin, a key Cdk1 substrate. Notably, restoration of Cdk1 activity rescued lamin phosphorylation, thereby mitigating lamin aggregation. Furthermore, persistence of lamin aggregation during mitotic entry correlated with premature reassembly of lamin during mitotic exit, affecting nuclear envelope reassembly. These findings collectively suggest that ROS-mediated perturbation of Cdk1 activity during early mitosis can trigger lamin aggregation that affects lamin reassembly, thereby disrupting nuclear morphology. Our study elucidates a novel mechanism by which ROS can disrupt nuclear architecture by modulating Cdk1 activity during mitosis. [BMB Reports 2026; 59(1): 69-77].

Evolution has tuned epigenetic resilience to preserve chromatin organization, transcriptional networks, and cellular identity under relentless stress. Over time, however, all eukaryotic life faces an inevitable rise in entropy that erodes the chromatin landscape at the genomic scale. This entropic decay of epigenetic information, epigenetic aging, is a primary driver of biological aging and systemic dysfunction. The brain is particularly vulnerable to epigenetic aging, with post-mitotic neurons accumulating lifelong chromatin erosion, and the glial epigenome drifting toward pro-inflammatory states. Defining the drivers and consequences of epigenetic aging in the brain forms the basis for restoring youthful chromatin landscapes, cellular identity, and cognitive capacity. [BMB Reports 2026; 59(1): 27-39].

Left-right determination factor 2 (Lefty2) is a transforming growth factor-β (TGF-β) receptor ligand that is critical for organ asymmetry and cell proliferation. More broadly, the TGF-β superfamily plays indispensable roles in development and gene regulation, and TGF-β family ligands are instrumental in osteoclast differentiation and bone resorption. In the present study, we show that Lefty2 dramatically inhibits receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation. We found that this effect was associated with inhibition of early intracellular signaling pathways activated by RANKL, which are important for osteoclast differentiation. Furthermore, administration of exogenous Lefty2 prevented RANKLinduced bone loss in mice. Interestingly, transgenic mice expressing Lefty2 controlled by the Mx-1 promoter did not show a distinct bone phenotype, even though transgenic mouse-derived bone marrow macrophages exhibited reduced osteoclast formation compared to controls in vitro. [BMB Reports 2026; 59(1): 78-83].

Aging is a multifactorial and heterogeneous biological process, where chronological age alone does not accurately reflect an individual's functional or physiological state. The emerging discipline of precision geronutrition integrates the principles of geroscience with precision nutrition, aiming to delay the onset of age-related functional decline by modulating fundamental molecular mechanisms, such as nutrient-sensing pathways (mTOR, AMPK, and sirtuins), inflammaging, and oxidative stress. A major barrier to progress has been the absence of validated biomarkers that can quantify biological aging and assess intervention efficacy. Recent advances in biological aging clocks, in particular DNA methylation-based epigenetic clocks, provide powerful tools to objectively measure biological age, and evaluate the impact of nutritional interventions. This review discusses how personalized dietary strategies, guided by multi-omics data (genomic, metabolomic, and microbiome profiles), can decelerate aging trajectories. We propose that individualized daily nutrition, aligned with an individual's unique biological characteristics, represents a targeted and actionable approach to extend healthspan. The integration of dynamic aging clocks into nutritional intervention frameworks will be essential to transition from a diseaseoriented model to a preventive, healthspan-centered paradigm. Future challenges include large-scale clinical validation, standardization of aging biomarkers, cost reduction, and translation into public health and clinical applications. [BMB Reports 2026; 59(1): 51-59].

Most in vivo neural technologies have been developed to either enhance the resolution for capturing subcellular neuronal activity or to expand the spatial range for tracking the populational ensemble of neurons in the brains of live animals. While these prevailing approaches hold great promises for elucidating cellular and circuit functions in behaving mammals, the cross-sectional observation is inherently limited in its ability to fully account for the causal interactions of neural dynamics across multiple scales of brain architecture. Therefore, the simultaneous observation of multi-scale neural activity has emerged as a crucial strategy to provide a more holistic understanding of brain function. These advancements enable the simultaneous detection of diverse signals, offering unprecedented insights into the dynamic neurophysiological mechanisms across three-dimensional brain structures that have not yet been fully elucidated. In this review, we review the state-of-the-art technologies for the parallel observation of multiple neural targets in vivo. We next highlight strategies for the simultaneous observation of brain signals at multiple resolutions, aiming to bridge the spatiotemporal gaps between the microscopic and macroscopic domains of neurobiology. We also focus on the technical integration of neural tools to acquire simultaneously electrophysiological activity or optical imaging, leveraging their complementary strengths. Finally, we discuss the future challenges and potential prospects of multimodal neural techniques, paving the way for a more comprehensive understanding of the brain functions and disorders.

Deep mutational scanning (DMS) enables systematic evaluation of protein sequence-function relationships, but its utility is often limited by the complexity of library construction. Existing mutagenesis strategies are either biased, labor-intensive, or prone to design errors, restricting their scalability for comprehensive variant generation. Here, we present a systematic cloning framework coupled with an automated Python-based pipeline for oligonucleotide design in DMS library construction. Our strategy employs restriction enzyme-guided tiling to partition coding sequences into manageable fragments, ensuring uniform coverage and compatibility with standard cloning workflows. The pipeline supports both strict and relaxed design modes, minimizes redundancy, and incorporates silent mutations to prevent restriction site conflicts. This platform optimizes library design efficiency, improves accuracy, and provides a flexible framework adaptable to diverse genes and experimental contexts. By integrating molecular cloning constraints with computational automation, our method offers a scalable and accessible solution to accelerate DMS library construction and functional genomics studies.

Long non-coding RNAs (lncRNAs) are now recognized as being pivotal regulators that enable the fine-tuned control of gene expression. While the functional diversity of lncRNAs challenges comprehensive understanding of their mechanisms, recent advances have revealed how these molecules coordinate epigenomic control, ranging from local chromatin regulation to large-scale nuclear organization. By scaffolding, recruiting, or antagonizing transcription factors and chromatin-modifying complexes, lncRNAs shape chromatin states, including histone modifications and DNA methylation patterns. In parallel, lncRNAs regulate three-dimensional genome architecture by modulating chromatin loops, topologically associating domains, and nuclear compartments. These regulatory mechanisms frequently operate in a coordinated manner, as exemplified by X chromosome inactivation, in which lncRNAs direct chromosome-wide silencing through combined epigenetic reprogramming and architectural remodeling. This review synthesizes current mechanistic insights into how lncRNAs integrate chromatin modification with architectural regulation to achieve spatiotemporal gene expression, and highlights how lncRNA dysregulation contributes to human disease. We provide an integrative perspective on how lncRNAs link epigenetic programs with genome topology to control normal physiology and pathogenesis.