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Fuellen et al. (2025) highlighted the essential role of explainable AI methods, particularly principal component analysis (PCA), in evaluating interventions for aging and longevity. However, this paper raises significant concerns regarding PCA's linear and parametric nature, which can misrepresent complex, nonlinear data common in geroscience research. As biological relationships often defy simplistic interpretations, reliance on PCA may obscure vital insights, leading to potential...

The core mechanism of skeletal aging lies in the comprehensive disruption of microenvironmental homeostasis, involving a multidimensional interactive network comprising immune cells, mesenchymal stem cells, and their differentiated lineages. Although osteoporosis (OP) and osteoarthritis (OA) have traditionally been viewed as distinct degenerative disorders, recent breakthroughs in osteoimmunology reveal their shared immune-aging mechanism: immune cell dysfunction within the bone marrow...

The role of tubular epithelial cells (TEC) senescence in the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remains debated due to the complexity of senescent cell populations and their pro-survival mechanisms. To directly assess the contribution of TEC senescence to AKI-to-CKD progression, we employed an aristolochic acid nephropathy (AAN) mouse model. Here, we demonstrated that AAI-induced DNA damage specifically drives TEC senescence during AKI-to-CKD progression....

The ultra-slow relaxation dynamics of glasses at ambient temperature provide a promising alternative for dating glasses with extremely low isotopic content that cannot be dated using traditional radiometric methods. However, these ultra-slow, nonlinear aging dynamics remain poorly understood due to the lack of accurate theoretical models and long-term experimental validation. Existing equilibrium-based dynamics models substantially overestimate relaxation times at temperatures far below the...

CONCLUSION: 24-week HIIT intervention can effectively delay the decline of renal function and the progression of renal fibrosis in naturally aging rats. Its protective effect may be associated with inhibiting the overactivation of the TGF-β1/Smad signaling pathway. High-volume HIIT (H1) induced a more profound suppression of the pro-fibrotic pathway, whereas low-volume HIIT (H2) represents a time-efficient strategy conferring notable protection at the phenotypic level.

CONCLUSION: Plasma biomarkers may reflect stage-specific mobility changes in aging populations. Their integration with performance-based tests may support early identification of functional decline and guide timely interventions.

Timely infiltration and effective turnover of macrophages after trauma are essential for wound regeneration. In pathological conditions, such as diabetic wounds, how disturbances in cellular collaboration leads to persistent inflammatory infiltration remains unclear. Herein, we identify that the expression of methionine adenosyltransferase 2 A (MAT2A), which is downregulated in pericytes, is negatively correlated with inflammatory macrophage infiltration in diabetic wounds. Cspg4-CreER^(T2)/+;...

Aging studies have entered a transformative era with the discovery and application of short peptides as regulators of senescence. These short peptides are encoded by small open reading frames in nuclear, mitochondrial, and viral genomes. Unlike non-coding RNAs, short peptides are evolutionarily conserved and play a role in ameliorating decline of cellular function. It has now been recognized involved in nearly all biological processes, including diseases and senescence, however, the mechanisms...

The liver plays a central role in regulating systemic metabolism, and its function declines with age, contributing to increased susceptibility to metabolic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by hepatic lipid accumulation and inflammation, is an early manifestation of liver dysfunction strongly associated with aging, insulin resistance, and high-fat diet (HFD) consumption. Ames Dwarf mice, which are growth hormone (GH)-deficient and...

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Epigenetic drift is a key feature of aging and is associated with age-related diseases including cancer, yet the underlying molecular mechanisms remain unclear. Here, by analyzing DNA methylation and gene expression data from healthy and cancerous human colon samples, we identify an aging and colon cancer-associated DNA methylation (DNAm) drift. We find evidence that this drift is conserved in the mouse intestinal epithelium, where we demonstrate its origin within intestinal stem cells and...

Aging and age-related diseases share convergent pathways at the proteome level. Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the UK Biobank (n = 43,616) and validated their high accuracy in cohorts from China (n = 3,977) and the USA (n = 800; cross-cohort r = 0.98 and 0.93). Accelerated organ aging predicted disease onset, progression and mortality beyond clinical and genetic risk factors, with brain aging being most strongly...

Intraneuronal aggregates of the microtubule-associated protein tau play a pivotal role in Alzheimer's disease and several other neurodegenerative syndromes. Anti-tau antibodies can reduce pathology in mouse models of neurodegeneration and are currently being tested in humans. Here, we performed a large-scale seroepidemiological search for anti-tau IgG autoantibodies (ατ) on 40,497 human plasma samples. High-titer ατ+ individuals were surprisingly prevalent, with hospital patients being three...

Recent advances in ultra-accurate sequencing technologies have revealed that somatic mutations accumulate throughout the human lifespan and may contribute to both normal aging and disease. These mutations are highly diverse, often non-recurrent, and functionally heterogeneous, making their biological impact difficult to evaluate systematically. Although many studies have profiled somatic mutations in individual tissues or limited cohorts, a centralized and scalable platform that integrates...

Lung adenocarcinoma (LUAD), the most prevalent form of lung cancer, is characterized by aggressive growth, immune resistance, and high tumor heterogeneity. Here, we demonstrate that genetic loss of protein kinase Cι (PKCι), which is found in ∼20% of LUAD patients, alters the trajectory of mouse Kras/Trp53-driven LUAD tumors from one resembling lung development to one mimicking lung regeneration. As a result, a major subset of tumor cells with PKCι loss exhibit cellular senescence and...

The telomerase RNA-protein enzyme is critical for most eukaryotes to complete genome copying by extending chromosome ends, thus solving the end-replication problem and postponing senescence. Despite the importance of the fission yeast Schizosaccharomyces pombe to biomedical research, very little is known about the structure of its 1212 nt telomerase RNA. We have determined the secondary structure of this large RNA, TER1, based on phylogenetics and bioinformatic modeling, as well as genetic and...

Synapses must be resilient to the challenges they confront during development, experience, disease, and aging. A conserved form of adaptive plasticity, observed at the glutamatergic Drosophila neuromuscular junction (NMJ), is expressed following acute pharmacological blockade of postsynaptic glutamate receptors (GluRs). This challenge is counteracted by enhanced presynaptic neurotransmitter release to maintain stable synaptic strength. This retrograde form of homeostatic plasticity is termed...

The abnormal protein degradation implicated in the pathogenesis of Parkinson's disease was previously attributed to defective H+ leakage from lysosomes via TMEM175 (https://doi.org/10.1016/j.cell.2022.05.021). In this issue, Riederer et al. (https://doi.org/10.1083/jcb.202501145) demonstrate that TMEM175 is instead a K+ channel, minimally permeable to H+.

DNA recovered from people buried at the site reveals surprises

Identity of the toe bones and other fossils could shake up the human family tree