Aging & Longevity

Global understanding of arterial aging remains limited despite its well-recognized medical and economic impact, hindering the development of effective mitigation strategies. The aorta, the major elastic artery, experiences a loss of homeostasis during aging that results from highly complex interactions. A promising approach to unravel the underlaying mechanisms is to investigate how aging affects the aortic transcriptome, leveraging the tremendous technological advances in RNA sequencing...

CONCLUSION: Combining aerobic exercise with cognitive training improves clinical outcomes in older adults with MCI and may influence stress-related neurobiological pathways. This multimodal approach represents a promising, non-pharmacological strategy for mitigating age-related cognitive decline.

CONCLUSION: Liver fat accumulation and fibro-inflammation were associated with higher brain-PAD, with fibro-inflammation playing a key role. These associations may be attenuated in individuals with optimal lifestyle behaviors, suggesting a potentially modifiable target for intervention.

CONCLUSION: Socioeconomic disadvantages, reflected in lower education, income, and employment, were associated with a higher incidence of depressive symptoms. Addressing these inequalities within integrated chronic disease and mental-health care may help prevent late-life depression.

Ceramides regulate diverse cellular processes through compartment-specific accumulation. While mitochondrial ceramide accumulation promotes apoptosis, its regulation and function during senescence remain incompletely understood. Here, we integrate lipidomics, transcriptomics, Raman spectroscopy, and biochemical characterizations to define sphingolipid remodeling in replicative senescence. Senescent cells exhibit elevated ceramide levels and depletion of very-long-chain sphingomyelins, despite...

Radiotherapy (RT)-induced senescent tumor cells (STCs) reinforce an immunosuppressive tumor microenvironment (ITM) and compromise therapeutic outcomes. However, current senolytic strategies lack specificity for STCs and often cause off-target toxicity. Here, we observe that STCs possess enhanced antigen-presenting capacity in patient-derived tumor tissues and murine tumor models. Leveraging this phenomenon, we engineer STC-derived nanovesicles (termed nano-APM) for preserving endogenous antigens...

The accumulation of senescent cells in white adipose tissue (WAT) is closely associated with the functional decline of WAT and plays a causal role in the pathogenesis of metabolic diseases. Therefore, the elimination of senescent cells in WAT holds promise for the treatment and prevention of age-related metabolic diseases. Using a drug-repositioning strategy for 2150 clinically applied compounds, we discover that homoharringtonine (HHT), an FDA-approved anti-leukemic drug, manifests...

Long noncoding RNAs (lncRNAs) regulate transcriptional and epigenetic programs during aging and senescence. However, no comprehensive studies have systematically integrated multilayered analyses to reveal their diverse regulatory roles. Moreover, lncRNAs with therapeutic potential in age-related diseases remain unexplored. Here we systematically perturbed 32 high-abundance aging- and senescence-associated lncRNAs (PtbAlncs) using a Perturb-seq-based CRISPR-dCas9-KRAB knockdown system coupled...

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Immune responses vary between individuals due to age, sex, genetics, and environment, yet most systems immunology studies focus on populations of European ancestry. To address this gap, we established the Healthy Human Global Project - Hong Kong (HHGP-HK) to characterize immune variability in a healthy Asian population. Modeled on the French Milieu Intérieur study, we adapted inclusion and exclusion criteria and collected harmonized demographic, medical, and lifestyle data for cross-cohort...

Chimeric antigen receptor (CAR) T cells have transformed hematologic cancer therapy but remain limited in solid tumors by antigen heterogeneity and a suppressive, pro-fibrotic microenvironment. We previously identified the urokinase plasminogen activator receptor (uPAR) as upregulated in senescent, pro-fibrotic cells and showed that uPAR-directed CAR T cells could safely reverse fibrosis in mice. Integrative analyses now reveal that uPAR is broadly expressed in solid tumors enriched for TP53 and...

Phenotyping cells at transcriptomic and proteomic levels is an essential step to understanding cellular contributions to development, aging, injury, and disease. Since proteome and transcriptome level abundances modestly correlate, complementary profiling of both is needed. We report a method called simultaneous protein and RNA -omics (SPARO) to capture the cell type-specific transcriptome and proteome simultaneously in vitro using BV2 microglial and HEK293 cell lines and in vivo using...

Co-pathology is a common feature of neurodegenerative diseases that complicates diagnosis, treatment and clinical management. However, sensitive, specific and scalable biomarkers for in vivo pathological diagnosis are not available for most neurodegenerative neuropathologies. Here we present Proteomics-based Artificial Intelligence for Dementia Diagnosis (ProtAIDe-Dx), a deep joint-learning model on 17,187 patients and controls (age of 70.3 ± 11.5 years, 53.2% female), that uses plasma...

Breast cancer can develop over a wide age range and tumors in younger women differ from those in older women. Aging alters the spatial context of early tumors and may explain these differences, but breast tissue aging remains poorly characterized. Here, using imaging mass cytometry to profile the spatial expression of 40 proteins, we explore age-related remodeling of normal breast tissues in over 3 million cells from 527 reduction mammoplasties. Aged breast tissue was less cellular and less...

The coordination of proteostasis between the brain and peripheral tissues is essential for the health and survival of all animals. In C. elegans, glia coordinate organismal proteostasis and longevity via the unfolded protein response of the endoplasmic reticulum (UPR^(ER)). However, the signaling molecules required remain unknown. Here, we show that glial UPR^(ER) activation increases levels of specific neuropeptides. We identify a single neuropeptide, FLP-17, that is sufficient but not...

Mammals are constantly exposed to various stressors of internal and external origin. Though hair follicles (HFs) are exquisitely sensitive to stress, it remains largely unknown how stress-induced responses are linked with the intrinsic regulators of HF growth, cycling, and regeneration. Here, we characterize the long-range enhancer of Sonic hedgehog (Shh) gene which encodes a crucial mitogen in the HF, and identify a hair stress-responsive enhancer (HSRE) as a unified target on which various...

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In our society, the aging of the population is a major public health concern. Recently we have identified a new snoRNA (jouvence) in Drosophila, and showed that its deletion (F4) reduces lifespan, while its overexpression increases it. F4 deleted flies also present neurodegenerative lesions and a deregulation of metabolic parameters such as triglycerides and sterols. However, a deeper characterization of this genomic locus has revealed the presence of two additional snoRNAs. Here, we have...

Delirium is a common and severe neuropsychiatric syndrome with lasting cognitive consequences, yet its pathophysiology remains poorly understood. We hypothesize that impaired glymphatic flow represents a central mechanism by which delirium evolves. This hypothesis builds on recent evidence showing that major delirium risk factors, such as ageing, dementia, cardiovascular disease and renal failure, are all associated with reduced glymphatic clearance. Similarly, common delirium triggers,...