Aging & Longevity

As age is a significant risk factor for multiple neurodegenerative diseases, investigating normal brain aging may help identify molecular events contributing to increased disease risk over time. Single-nucleus RNA sequencing (snRNA-seq) enables analysis of gene expression changes within specific cell-types, offering insights into the molecular mechanisms underlying aging. However, most brain aging snRNA-seq datasets use age-matched controls from studies focused on pathology and sample cortical...

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Cellular senescence is a hallmark of age-related disorders, including cancer, in which senescence contributes to tumor progression and treatment resistance. Targeting senescent cells therapeutically requires noninvasive methods to longitudinally monitor senescence burden. Here, we present an injectable nanoprobe for noninvasive detection of therapy-induced senescence in lung cancer and pulmonary fibrosis via urine testing. Using human biopsy samples, clinical transcriptomic datasets and mouse...

Optimal sleep has a vital role in promoting healthy ageing and enhancing longevity. Here we propose Sleep Chart to assess the relationship between self-reported sleep duration and 23 biological ageing clocks derived from in vivo imaging¹, plasma proteomics² and metabolomics³. First, a systemic, U-shaped pattern emerges between sleep duration and biological age gaps across nine brain and body systems and three omics technologies. The sample-specific lowest biological age gaps are achieved between...

The human brain relies on a complex network of connections to function, with white matter acting as the primary communication highway between different brain regions^(1,2). Disruptions in these critical communication pathways are linked to several neurological, psychiatric and developmental disorders^(3,4). Although clinicians have long used standard growth charts to track physical development⁵, with more recent work translating these to whole-brain and grey matter measurements^(6-9), there has...

Genomic stability is critical for cellular function; however, in the central nervous system, highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion...

Transition toward senescence is a cellular response to various forms of stress. This phenomenon is evolutionarily conserved across species, from insects to humans. Senescent cells (SCs) permanently withdraw from the cell cycle and undergo physiological changes, notably the acquisition of a robust secretory activity characterized by the release of numerous molecules, including cytokines, chemokines, and metalloproteinases. Through this program, termed Senescence-Associated Secretory Phenotype,...

Impaired immune clearance of senescent fibroblasts is a putative driver of pulmonary fibrosis. Exhausted natural killer (NK) cells have been implicated in this process, yet the underlying immune evasion mechanisms remain poorly understood. Using single-cell RNA sequencing (scRNA-seq) and spectral flow cytometry, we identified natural killer group 2 member A (NKG2A) as the predominant inhibitory checkpoint receptor expressed on NK cells in fibrotic lung diseases. Mechanistic in vitro coculture...

Although mitochondrial function is essential for life in multicellular organisms, work from multiple model organisms has demonstrated that a mild impairment of mitochondrial function can increase lifespan. In C. elegans, a mutation in the isp-1 gene, which encodes the Rieske iron sulfur protein in Complex III of the mitochondrial electron transport chain, results in increased lifespan, enhanced resistance to stress and slow physiologic rates. While the molecular mechanisms involved are...

Advanced age is a well-known risk factor for severe complications in surgical patients with critical illnesses, partly due to declined intestinal mucosal defense, but the underlying mechanism remains largely unknown. Our study provided direct evidence from older human and mouse small intestines of the adverse impact of aging on Paneth cell functionality by impaired mitochondrial metabolism. Mechanistic investigation revealed a specific elevation of Paneth cell enriched microRNA-152 (miR-152) in...

Almost a century ago, calorie restriction (CR) was identified as a robust intervention for extending lifespan and healthspan, a discovery that captured the imagination of both scientists and the public. If the powerful mechanisms engaged by CR can be uncovered and harnessed through a pill, humans might be able to live longer and healthier lives. Here, we will discuss the evolution of rapamycin, an inhibitor of the mTOR (mechanistic Target Of Rapamycin) protein kinase, from an immunosuppressant...

Canine Cognitive Dysfunction (CCD) is a progressive neurodegenerative condition of ageing dogs, sharing pathological and clinical features with Alzheimer's disease. Despite the growing prevalence of CCD, non-pharmacological interventions for affected companion animals remain underexplored. This study evaluated the effects of structured group training classes on signs of CCD, sleep, daily activity, and caregiver burden. Forty-two dogs (≥ 8 years) with mild to moderate CCD were enrolled in either...

Elderly patients exhibit heightened susceptibility to postoperative complications following general anesthesia and surgery, yet the molecular mechanisms driving this age-dependent vulnerability remain poorly defined. We performed RNA sequencing on olfactory bulb (OB), hippocampus (HI), lung, and spleen from young (3-month, m), late middle-aged (17 m), and geriatric (27 m) male C57BL/6 mice 24 h after 2 h of exposure to isoflurane anesthesia and laparotomy (ISO/OP). Short-term ISO/OP elicited...

CONCLUSION: These findings highlight ongoing uncertainties and cultural variations in antibiotic prescribing practices at the end of life, highlighting the need for clinical decision-support tools and educational resources directed not only at physicians, but also at nursing teams, families, and caregivers. In the context of an aging population and rising antimicrobial resistance, a deeper understanding of the factors influencing antibiotic use in palliative care is essential to inform the...

CONCLUSIONS: This study highlights the critical role of age-friendly urban environments in supporting the mental health of older adults. Urban planning should prioritise accessible green spaces, elderly-friendly housing, inclusive leisure opportunities, and improved access to life information. Promoting social respect and volunteer engagement can further enhance emotional well-being. These findings provide empirical support for implementing the WHO Age-Friendly Cities Framework as a strategic...

CONCLUSIONS: The findings of this study highlight central ADL and IADL items within the functional network of older adults living alone. These results provide insights into the interrelationships among functional abilities and may guide future research on strategies to support or prevent functional decline in this population.

CONCLUSIONS: This study shows that considering healthy ageing from the perspective of functional ability rather than focusing on chronological age has the potential to more precisely address those community-dwelling older people living with functional decline, frailty or disability who are most vulnerable in heat situations. The measurement of functional ability by screening community-dwelling older people with a self-administered questionnaire on functional resources and risks proved to be a...

CONCLUSION: Adverse trajectories of depressive symptoms, particularly persistent and increasing patterns, are consistently associated with elevated osteoarthritis risk across diverse populations. These findings underscore the importance of longitudinal mental health monitoring and suggest that early intervention for depressive symptoms may represent a modifiable pathway for osteoarthritis prevention. The observed effect modification patterns highlight the need for population-specific and...

CONCLUSION: The interpretable machine learning framework based on dietary antioxidant profiles can robustly predict accelerated biological aging. XGBoost demonstrated the best performance in predicting accelerated aging risk. Daidzein, apigenin, magnesium, zinc, and vitamin E are core dietary antioxidants closely associated with a reduced risk of accelerated biological aging. This study provides analytical reference at the large population level for the development of nutritional intervention...