Aging & Longevity

Meiotic maturation of vertebrate oocytes occurs in the near-absence of transcription. Thus, female fertility relies on timely translational activation of maternal transcripts stockpiled in full-grown prophase-I-arrested oocytes. However, how expression of these mRNAs is suppressed to maintain the long-lasting prophase-I arrest remains mysterious. Utilizing fast-acting TRIM-Away, we demonstrate that acute loss of the translation repressor 4E-T triggers spontaneous release from prophase-I arrest...

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The mechanisms through which mutations in splicing factor genes drive clonal hematopoiesis (CH) and myeloid malignancies, and their close association with advanced age, remain poorly understood. Here we show that telomere maintenance plays an important role in this phenomenon. First, by studying 454,098 UK Biobank participants, we find that, unlike most CH subtypes, splicing-factor-mutant CH is more common in those with shorter genetically predicted telomeres, as is CH with mutations in PPM1D...

The comparative biology of aging leverages the remarkable diversity in aging rates and lifespans across species to uncover naturally evolved adaptations that promote longevity, disease resistance and injury resilience. The beauty of comparative biology is that it discovers adaptations that evolved outside of the protected laboratory environment, shaped by natural selection under real-world pressures. In this Review, we outline key approaches in comparative biology of aging studies, including the...

Maternal malnutrition affects millions of people worldwide in two main ways: through food insecurity and hunger, as well as through diets high in ultra-processed, low-nutrient foods. These effects are often linked to deficiencies in specific macronutrients and micronutrients, which can lead to organ-specific consequences in the biological development of the child-a context explored within the framework of the Developmental Origins of Health and Disease (DOHaD). Given the extensive effects of...

CONCLUSION: This study identifies specific sEMG-derived features, particularly signal shape and complexity metrics, as potential non-invasive biomarkers for neuromuscular decline in sarcopenia. The Post-stab epoch emerges as a sensitive window for detecting deficits in motor control, supporting the use of perturbation-based tasks and sEMG analysis for early detection, monitoring, and intervention planning in aging populations.

CONCLUSIONS: This systematic review and meta-analysis suggests that homeless individuals have a dementia prevalence higher than population-based studies of housed adults of a similar age, where the estimated prevalence is under 3%. Research on models of care aimed at reducing homelessness in those experiencing dementia is needed.

As the population of individuals living with Alzheimer's disease and related dementias (AD/ADRD) continues to grow, so does the need for a well-prepared and stable dementia care workforce. The National Dementia Workforce Study (NDWS) represents a significant investment to understand the demographics, experiences, and magnitude and scope of challenges faced by the professional and direct care workforce providing care to people with dementia. This article discusses the NDWS's goals, data...

CONCLUSIONS: In this French cohort, SCORE2-OP overestimated cardiovascular risk and showed moderate discrimination. EDS improved SCORE2-OP performance in intermediate cardiovascular risk groups where treatments are uncertain, highlighting its clinical relevance; although implications for prevention strategies require further study.

Centenarians exhibit remarkable disease resilience despite chronic low-grade inflammation. We investigated the inflammation-related proteome response to acute exercise in seven centenarians (100-104 years). Exercise downregulated 52 proteins (e.g., TNF, IL10, IL1RN, CCL family members) involved in immune cell trafficking, apoptosis, and cytokine regulation. Even at the extreme end of the lifespan, humans retain molecular responsiveness to exercise, with modulation of inflammation-related...

Telomeres protect the chromosome ends from deleterious DNA damage response and repair activities. In humans, telomerase maintains telomere length in germ and stem cells, but not in most somatic cells. Consequently, telomeres shorten with cell division and age, limiting cell proliferation and protecting against cancer. When telomeres become critically short, they may also cause senescence, inflammation, and organ failure, which are major drivers of aging. Therefore, maintaining an optimal,...

Cellular senescence is a state of persistent cell cycle arrest and is a critical contributor to arterial aging. The primary drivers of cellular senescence are the DNA damage response (DDR) and telomere dysfunction, which is induced by increasing exposure to DNA-damaging stimuli such as atheroprone shear stress. While late-life aerobic exercise is an effective intervention to mitigate arterial aging, its specific impact on the DDR and telomere dysfunction is unknown and may not show uniform...

Worldwide, more than 4 million patients with end-stage kidney disease require hemodialysis through an arteriovenous fistula (AVF). AVFs fail because of venous neointimal hyperplasia (VNH) resulting in venous stenosis formation. A phase 1 randomized trial in patients undergoing upper extremity AVF placement was performed to evaluate the safety and efficacy of autologous adipose-derived mesenchymal stem cells (MSCs) in improving AVF function. The mechanism of action by which MSCs exert their...

L-3,4-dihydroxyphenylalanine (L-DOPA), a naturally occurring tyrosine derivative, is prevalent in environments that include mosquito habitats, potentially serving as part of their diet. Given its role as a precursor for melanin synthesis we investigate the effect of dietary L-DOPA on mosquito physiology and immunity to Plasmodium falciparum and Cryptococcus neoformans infection. Dietary L-DOPA is incorporated into mosquito melanin via a non-canonical pathway and has a profound transcriptional...

The function of osteoporosis-induced bone marrow adipocyte (BMAds) accumulation remains inadequately understood. Here, we analyze bone marrow lipidomic data and reveal that BMAds deteriorate the skeletal microenvironment by secreting large amounts of lipids, altering the senescence status of neighboring cells by affecting their mitochondrial function. To specifically target BMAds under osteoporotic conditions, we design a polycation-loaded biomimetic dual-site framework (CZP@LC) that interferes...

Perturbations in protein quality control lead to the accumulation of misfolded proteins and protein aggregates, which can compromise health and lifespan. One key mechanism eliminating protein aggregates is aggrephagy, a selective type of autophagy. Here we reveal that fragmentation is required before autophagic clearance of various types of amorphous aggregates. This fragmentation requires both the 19S proteasomal regulatory particle and the DNAJB6-HSP70-HSP110 chaperone module. These two...

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Circadian rhythms are essential biological systems operating on a 24-h cycle, playing a crucial role in regulating sleep, cognitive function, immune responses, and hormone secretion. This review explores the intricate relationship between circadian rhythms and aging, with a focus on the underlying molecular mechanisms. It discusses age-related changes in sleep patterns and the role of circadian disruption in the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's....

BACKGROUND: In an ageing society, most older adults who require long-term care are still living in their homes and communities. Their families are burdened by caregiving duties, but their unique needs are often overlooked. In response to the increasing needs of respite care, the Jockey Club Stand-by-U (JC Stand-by-U) Caregivers Community Support Project aims to study the family caregivers' needs and how to best support them in the context of Hong Kong.

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP(2)) into inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca^(2+) release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven...