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Sun, Fu, Zheng, Hong, Liu et al. generate a single-nucleus transcriptomic atlas of the primate cochlear aging, identifying an age-related decline in Slc35f1 and showing that silencing Slc35f1 in mice induces hair cell degeneration and auditory deficits.

Through multimodal analyses of human cardiac tissues across different ages, Fan, Zheng, Zhan, Xu, Liu and colleagues reveal that RNA-binding protein ARID5A drives inflammaging by stabilizing the MAVS mRNA and activating the NF-κB–TBK1 pathway, and show that inactivating myocardial ARID5A attenuates cardiac senescence and functional decline.

SIRT5 protects against primate skeletal muscle ageing through TBK1 desuccinylation, which inhibits the downstream inflammatory and senescent phenotypes.

UDA-seq incorporates a post-indexing step to enhance the throughput of droplet-based single-cell multimodal sequencing, enabling efficient large-scale single-cell analysis.

Motor neuron senescence and neuroinflammation with microglial hyperactivation are intertwined hallmarks of spinal cord ageing.

Fanconi anaemia (FA) is a genetic disease associated with low levels of blood stem cells. Here Liu et al.report an improved method to generate genetically corrected induced pluripotent stem cells from an FA patient, and perform a screening to identify drugs that improve their differentiation into blood stem cells.

This large study, conducted in school-aged children in China, evaluates the relationship between long-term exposure to ambient particulate matter and positive screening for attention deficit hyperactivity disorder (ADHD). The authors report stronger associations between ADHD and PM₁ exposure than between ADHD and PM_2.5.

Ye et al. characterize the cardioprotective effect of SIRT2 in primates and reveal an important role for the SIRT2–STAT3–CDKN2B regulatory axis in primate cardiac aging, improving understanding of the epigenetic mechanism governing cardiac aging.

The authors characterized m⁶A dynamics in primate tissue aging and revealed a new role for the METTL3–m⁶A–NPNT axis in maintaining skeletal muscle homeostasis, thereby providing insight into the epitranscriptomic machinery underlying primate aging.

We introduce a major scientific endeavour called π-HuB (proteomic navigator of the human body), its aim being to generate and harness multimodality proteomic datasets to enhance our understanding of human biology.

Investigation of neural cells from post-mortem human brains and differentiated from patient-derived induced pluripotent stem cells shows that the LRRK2 mutation (G2019S) associated with familial and sporadic Parkinson's disease correlates with abnormalities at the nuclear envelope.

DGCR8 is a component of the canonical microprocessor complex for microRNA biogenesis. Here the authors implicate DGCR8 in heterochromatin maintenance and aging attenuation independent of its miRNA-processing activity through Lamin B1, KAP1 and HP1 interaction. DGCR8 overexpression can alleviate aging and senescence

Wang et al. generate a single nucleus-resolved transcriptomic atlas of primate adrenal aging, with which they demonstrate regional changes in adrenal aging, and establish the role of LDLR in impeding cholesterol uptake and DHEA-S production in aging.

Apolipoprotein E (APOE) is a lipoprotein particle component and is genetically linked to human longevity and Alzheimer’s disease; however, the mechanisms that link APOE and aging are incompletely understood. Here, Zhao et al. show that APOE drives cellular senescence in aged human mesenchymal progenitor cells by destabilizing heterochromatin.

The tumor suppressor PTEN is often mutated or lost in glioblastoma. Here, the authors demonstrate that in neuronal stem cells PTEN trans-represses PAX7gene expression and PTEN deficiency promotes PAX7-dependent neoplastic transformation.

Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells use a complex network of genetic and epigenetic pathways to maintain a delicate balance between self-renewal and multilineage differentiation. Studies using high-throughput genomic tools suggest that there is extensive crosstalk among epigenetic pathways that function at the level of DNA, histone and nucleosome. Mapping of higher-order chromatin structures and chromatin–nuclear matrix interactions provides insights into the three-dimensional organization of the genome and can reveal new rules of gene regulation.

Wiskott-Aldrich syndrome is caused by mutations in WASP, but the underlying mechanisms remain to be explored. Here the authors reveal that WASP deficiency results in aberrant RNA splicing, and that WASP regulates the transcription of splicing factor genes and co-transcriptional RNA splicing via a phase-separation process that involves splicing factors and nascent RNA.

The double-stranded DNA receptor AIM2 is able to sense the environmental pollutant perfluorooctane sulfonate, a prototypical perfluoro-alkyl substrate. Activation of the AIM2 pathway leads to inflammation and tissue damage via IL-1β secretion and pyroptosis of affected innate immune cells.

Arterial degeneration, closely associated with cardiovascular diseases, is driven by aging-related vascular cell-specific transcriptomics changes. This study provides a single-cell transcriptomic atlas for senile aortic and coronary arteries and underscores FOXO3A-based the transcriptional network in vasoprotection during aging.

A cynomolgus monkey model deficient in SIRT6 protein exhibits severe retardation in prenatal development, in which neuronal differentiation is delayed by activation of the H19 long non-coding RNA.

Wu et al. explore vaccine strategies targeting age-related diseases, as well as senescent cells specifically, as potential underlying drivers of aging itself. They discuss challenges faced in clinical trials, as well as further optimizations required to increase therapeutic efficacy.

Wang et al. analysed post-mortem samples of the lungs of patients with COVID-19 by bulk and single-nucleus RNA sequencing along with proteomics and discovered lung senescence as a feature of COVID-19 pathology.

Measuring reproductive aging in humans remains challenging. In this Perspective, Wang et al. summarize biomarkers for reproductive aging in clinical use, discuss age-linked molecular changes related to reproductive aging that could potentially serve as future biomarkers and highlight unresolved challenges and upcoming opportunities in the field.

Heterochromatin loss, telomere attrition and DNA damage induce cellular senescence by eliciting genome instability and innate immunity responses, thereby promoting ageing and age-related diseases. This Review discusses the underlying mechanisms of these processes and emerging cell-senescence therapeutics that target them.

A method for CRISPR-based genome editing that harnesses cellular non-homologous end joining activity to achieve targeted DNA knock-in in non-dividing tissues.

Ageing is characterized by the functional decline of tissues and organs and increased risk of ageing-associated disorders, and this decline is associated with epigenetic changes. Recently, ‘rejuvenating’ interventions, such as metabolic manipulation, partial cell reprogramming, heterochronic parabiosis and senescent cell ablation, have been proposed to extend healthspan and lifespan by modulating the epigenome.