Aging & Longevity

Primary human hepatocyte (PHH)-derived organoids form grape-like clusters with proliferative capacity, hepatocyte functionality, and multipolar polarity, serving as valuable models for liver biology and therapeutics. However, deriving comparable organoids from human embryonic stem cells (hESCs) remains difficult. Here, we established a defined system to differentiate hESC-derived hepatoblast organoids into hepatocyte organoids (heporgs) with two morphologies: spheroid-like (S-heporgs) and...

As climate warming accelerates, shifts in plant phenology are reshaping the functioning and stability of terrestrial ecosystems. While the roles of climatic drivers in shaping phenological responses to warming are well established, the influence of intrinsic plant functional traits remains poorly understood. Here, we combine two complementary approaches through a meta-analysis of 124 field warming experiments and an analysis of long-term phenological monitoring networks (CPON and USA‑NPN) to...

Calcium signalling in astrocytes is a fundamental mechanism for maintaining brain homeostasis, shaping neuronal activity, and coordinating vascular and immune responses. Once considered secondary to neuronal signalling, astrocytic Ca^(2+) dynamics are now recognized as highly versatile, spatially compartmentalized and essential for regulating neurotransmitter uptake, ion buffering, metabolic support and mitochondrial function. Accumulating evidence shows that these Ca^(2+) signalling pathways...

The New England Centenarian Study (NECS) provides a unique resource for the study of extreme human longevity (EL). To gain insight into biological pathways related to EL, chronological age and survival, we used an untargeted serum metabolomic approach (> 1400 metabolites) in 213 NECS participants, followed by integration of our findings with metabolomic data from four additional studies. Compared to their offspring and matched controls, EL individuals exhibited a distinct metabolic profile...

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CONCLUSION: This study will synthesize evidence from multiple studies on various electrical stimulation therapies for improving cognitive function in patients with mild cognitive impairment, thereby providing a diverse body of evidence to support clinical decision-making by physicians and optimization of treatment strategies for patients.

[This retracts the article DOI: 10.3389/fnagi.2017.00134.].

[This retracts the article DOI: 10.3389/fnagi.2017.00066.].

Endometriosis is a benign yet invasive disease characterized by ectopic endometrial growth and immune remodeling. While emerging evidence implicates cellular senescence in disease progression, the underlying mechanisms remain largely undefined. In this study, we identified marked heterogeneity in senescence across ectopic lesions and observed that P21-activated kinase 4 (PAK4) was consistently upregulated in senescent cells. Mechanistically, senescence induced PAK4 expression, which in turn...

Aging is a myeloid-biased process, i.e., the differentiation of myeloid cells increases, while the lymphoid lineage declines. Cellular senescence increases the secretion of inflammatory mediators which skew hematopoiesis toward myeloid cell generation. Myeloid cell nuclear differentiation antigen (MNDA) is a type-1 interferon (IFN)-inducible factor which is mainly expressed in the cells of the granulocyte-monocyte lineage, especially it is enriched in M2 macrophages and myeloid-derived...

Male reproductive aging is a complex physiological process characterized by progressive deterioration in spermatogenesis, hormonal imbalance, and increased susceptibility to infertility and genetic disorders. This review comprehensively summarizes the pivotal molecular mechanisms underlying testicular aging, with emphasis on mitochondrial dysfunction, oxidative stress, DNA damage, autophagy impairment, chronic inflammation, cellular senescence, and dysregulated apoptosis. Accumulating evidence...

CONCLUSION: We showed that increased USI values are associated with sarcopenia. This study shows USI as a sensitive, non-invasive marker for sarcopenia classification, supporting its use in clinical screening and monitoring of muscle changes in older adults.

Aging is a multifaceted process impacting physiological, genomic, metabolic, and immune functions. This study investigates the role of luminal fecal exosomes (LFEs) in age-associated metabolic dysfunction. We analyzed LFEs from young (3-month) and old (24-month) male and female C57BL/6 mice to characterize age-related differences in exosomal proteomic and miRNA cargos. To explore interactions between LFEs and the gut microbiome, naïve young mice were gavage fed with LFEs from old donors,...

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The integration of environmental cues into cellular programs is crucial for cell function. Yet, how this integration is modulated due to cellular aging remains unclear. We propose that the 3D chromatin organization filters these signals and investigated how age-related chromatin changes in human dermal fibroblasts affect responses to mechanical tension and TGF-β. Young fibroblasts exhibited synergistic gene expression enhancement in response to combined stimuli, a response that was markedly...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and maternal immune activation (MIA) is highly implicated in neuropathology and ASD-like phenotypes in offspring. However, the underlying regulatory mechanisms of ASD are multifactorial and remain largely unknown in MIA offspring. Here, we performed spatial transcriptome and single-nucleus RNA sequencing (snRNA-seq) analysis in MIA offspring brain to explore the neurobiological features of ASD. We obtained MIA-induced genes and...

Cell cycle progression presents a fundamental challenge to epigenome integrity, particularly due to the need to reestablish post-translational histone modifications (PTMs) following DNA replication. Although proliferative and differentiating tissues exhibit markedly different cell cycle dynamics, how these differences shape the histone modification landscape in vivo remains largely unexplored. Here, we show that levels of H3K27ac, H3K27me3, and H3K9me3 are tightly linked to cell cycle dynamics...

Tissues harbor memories of inflammation, which heighten sensitivity to diverse future assaults. Whether and how these adaptations are sustained through time and cell division remain poorly understood. We show that in mice, epidermal stem cells store lifelong, functional epigenetic records of psoriasis-like skin flares. Applying deep learning to investigate these chromatin dynamics, we unearth CpG dinucleotide density as a major driver of memory persistence. Although unnecessary for...

Aging is characterized by a decline in essential sensory functions, including olfaction, which is crucial for environmental interaction and survival. This decline is often paralleled by the cellular accumulation of dysfunctional mitochondria, particularly detrimental in post-mitotic cells such as neurons. Mitochondrial stress triggers the mitochondrial unfolded protein response (UPR^(MT)), a pathway that activates mitochondrial chaperones and antioxidant enzymes. Critical to the efficacy of the...