Aging & Longevity

Translational regulation in stress biology

1 week 1 day ago
Organisms must constantly respond to stress to maintain homeostasis, and the successful implementation of cellular stress responses is directly linked to lifespan regulation. In this Review we examine how three age-associated stressors-loss of proteostasis, oxidative damage and dysregulated nutrient sensing-alter protein synthesis. We describe how these stressors inflict cellular damage via their effects on translation and how translational changes can serve as both sensors and responses to the...
Naomi R Genuth

Fate mapping of peripherally-derived macrophages after traumatic brain injury in mice reveals a long-lasting population with a distinct transcriptomic signature

1 week 1 day ago
Traumatic brain injury (TBI) is an environmental risk factor for dementia and long-term neurological deficits, posing a significant public health challenge. TBI-induced neuroinflammation involves both brain-resident microglia and peripheral monocyte-derived macrophages (MDMs). Previous research has shown that MDMs contribute to the development of long-term memory deficits, yet their long-term behavior following brain infiltration remains unclear. To address this, our study uses two complementary...
Maria Serena Paladini

CTRP9 as a myokine mitigates sarcopenia via the LAMP-2A/NLRP3 pathway

1 week 1 day ago
Sarcopenia, a degenerative condition marked by progressive skeletal muscle atrophy and impaired regeneration, is closely associated with aging, chronic inflammation, and disrupted proteostasis. While macroautophagy has been extensively studied in this context, little of the role of chaperone-mediated autophagy (CMA) has been known. In this study, we identified C1q/TNF-related protein 9 (CTRP9) as a novel autocrine myokine secreted by skeletal muscle that exerts dual protective...
Linxi Li

CD4 T cells acquire Eomesodermin to modulate cellular senescence and aging

1 week 1 day ago
Aging is characterized by the progressive deterioration of tissue structure and function, leading to increased vulnerability to diseases. Senescent cells (SCs) accumulate with age, but how the immune system regulates their burden is unclear. Here we show that CD4 T cells differentiate into Eomesodermin (Eomes)^(+)CCL5^(+) T lymphocytes (CD4-Eomes) in a SC-rich environment and that a reduction in the SC load, achieved using senolytic drugs, was sufficient to halt this differentiation. We further...
Yehezqel Elyahu

Age differences in what-if thinking from midlife onwards: Prefrontal contribution and implications for emotional health in late life

1 week 1 day ago
Reduced counterfactual ("What-If") thinking (CFT) in late life is believed to reflect successful adaptation to limited resources for overcoming missed opportunities, thereby preventing feelings of regret. We propose that this adaptation becomes critical from midlife onwards, affects emotional regulation, and is mediated by the preserved functionality of the ventromedial prefrontal cortex (vmPFC). To test this, an epidemiological sample from the Hamburg City Health Study (N = 494), aged 48 to 75,...
Riccardo M Galli

A ternary-code DNA methylome atlas of mouse tissues

1 week 1 day ago
CONCLUSIONS: Our work reveals how tissue, sex, and age jointly govern the dynamics of the two cytosine modifications, augments the scope of DNA modification biomarker discovery, and provides a reference atlas to explore epigenetic dynamics in development and disease.
Sol Moe Lee

Synergistic effects of diabetes and sarcopenic obesity on cardiovascular disease risk in middle-aged and elderly Chinese adults: a large-scale prospective cohort study

1 week 1 day ago
CONCLUSIONS: The coexistence of diabetes and sarcopenic obesity synergistically increases cardiovascular disease risk beyond the effects of either condition alone in Chinese adults. These findings highlight the importance of comprehensive screening and integrated management strategies for individuals with both conditions to prevent cardiovascular complications.
Fang Wan

Inflammaging and the sex-frailty paradox

1 week 1 day ago
CONCLUSIONS: Trying to delineate the unique molecular profile of older women and men becomes essential for understanding the mechanisms underlying the sex-frailty paradox. Further research on sex-specific determinants is required to enhance our understanding of aging and develop effective strategies to promote health and longevity in both sexes.
Beatrice Arosio

When Melodies Cue Memories: Electrophysiological Correlates of Autobiographically Salient Music Listening in Older Adults

1 week 1 day ago
Autobiographical memory is essential for older adults, providing a foundation for self-identity. Although healthy aging is accompanied by changes in memory retrieval, musical memory remains relatively unaffected, suggesting music may serve as a cue for autobiographical memory recall. Autobiographically salient (ABS) music (i.e., deeply encoded songs associated with significant people, places, and events) is posited to engage distinct memory processes from familiar (FAM) music (i.e., songs that...
Veronica Vuong

Cisformer: a scalable cross-modality generation framework for decoding transcriptional regulation at single-cell resolution

1 week 1 day ago
Single-cell multiomic technologies enable the joint analysis of different modalities, but face challenges due to experimental complexity. Current computational methods for single-cell cross-modality translation lack biological interpretability. Here, we present Cisformer, a cross-attention-based generative model tailored for cross-modality generation between gene expression and chromatin accessibility at single-cell resolution. Systematic benchmarking demonstrates the superior accuracy and...
Luzhang Ji

Senescent macrophages in tumor: phenotypes, roles, and interventions

1 week 2 days ago
The senescence of immune cells, including macrophages, that accompany the initiation and development of tumors has become a novel research hotspot. Recently, studies have reported the molecular characteristics of senescent macrophages (sMACs) in the tumor microenvironment (TME), including cell cycle arrest, senescence-associated secretory phenotype (SASP), and senescence-associated β-galactosidase phenotype (SA-β-gal), and these characteristics not only suggest that sMACs are functionally rich...
Wenhui Shen

Comprehensive characterisation of age-related changes in cell subpopulations and tissue structural properties in secondary lymphoid organs

1 week 2 days ago
Population aging is an escalating global phenomenon, wherein age-related alterations in the human immune system exacerbate the susceptibility to diseases including infections and autoimmune disorders. Secondary lymphoid organs (SLOs) are key locations for the execution of immunological responses by mature immune cells; however, age-related changes in SLOs remain relatively understudied. To address this gap, this study employed comprehensive approaches including single-cell RNA sequencing...
Yuxin Deng

Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma

1 week 2 days ago
The exposome, an individual's lifelong environmental exposure, profoundly impacts health. Somatic tissues undergo functional decline with age, exhibiting characteristic ageing phenotypes, including hair greying and cancer. However, the specific genotoxins, signals and cellular mechanisms underlying each phenotype remain largely unknown. Here we report that melanocyte stem cells (McSCs) and their niche coordinately determine individual stem cell fate through antagonistic, stress-responsive...
Yasuaki Mohri

Translating cellular senescence research into clinical practice for metabolic disease

1 week 2 days ago
Translational research on cellular senescence has led to numerous early-phase clinical trials targeting senescent cells to treat, prevent or alleviate multiple disorders and diseases, including metabolic diseases and their comorbidities. Cellular senescence is a cell fate that occurs in response to stressors, including metabolic disruptions, and is one of the hallmarks (or pillars) of ageing. In their senescent state, cells cease proliferation and can develop a senescence-associated secretory...
Selim Chaib

HIF1 activity in photoreceptors drives type 3 neovascularization and retinal atrophy in a new mouse model of age-related macular degeneration

1 week 2 days ago
Morphological changes in the ageing eye impede oxygen delivery from the choroid to the outer retina causing tissue hypoxia, which activates a molecular response that adapts the transcriptomic fingerprint of the retina and retinal pigment epithelium (RPE). This response, orchestrated by hypoxia-inducible transcription factors (HIFs), leads to the production of pro-angiogenic factors and plays a critical role in the development and pathogenesis of age-related macular degeneration (AMD). To...
Fredy Geiger
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