Aging & Longevity

Age-Associated Decline in Autophagy Pathways in the Retinal Pigment Epithelium and Protective Effects of Topical Trehalose in Light-Induced Outer Retinal Degeneration in Mice

4 months 1 week ago
Age is a primary risk factor for chronic conditions, including age-related macular degeneration (AMD). Impairments in autophagy processes are implicated in AMD progression, but the extent of autophagy's contribution and its therapeutic potential remain ambiguous. This study investigated age-associated transcriptomic changes in autophagy pathways in the retinal pigment epithelium (RPE) and evaluated the protective effects of topical trehalose, an autophagy-enhancing small molecule, against...
Katherine Cox

Pulmonary V̇O2 on-kinetics and walking net V̇O2 associate with fatigue and mood disturbance in postmenopausal women

4 months 1 week ago
Postmenopausal women often experience fatigue and mood disturbance both of which interfere with quality-of-life. Since greater physical function aids psychosocial well-being, we hypothesized the acute cardiopulmonary responses during walking may reveal important factors linked to fatigue and mood disturbance. In this cross-sectional study, women of similar body mass index (BMI) aged 55-75 y were dichotomized to mid-life (55-65 y; 83.4 ± 8.4 kg/m²; n = 14) or older (≥65 y; 81.8 ± 10.4 kg/m²; n =...
Stephen J Carter

Genetic determinants of proteomic aging

4 months 1 week ago
Changes in the proteome and its dysregulation have long been known to be a hallmark of aging. We derived a proteomic aging trait using data on 1459 plasma proteins from 44,435 UK Biobank individuals measured using an antibody-based assay. This metric is strongly associated with four age-related disease outcomes, even after adjusting for chronological age. Survival analysis showed that one-year older proteomic age, relative to chronological age, increases all-cause mortality hazard by 13 percent....
Alexander Mörseburg

p53 protein degradation redefines the initiation mechanisms and drives transitional mutations in colorectal cancer

4 months 1 week ago
Incidence of colorectal cancer (CRC) is increasing likely due to different mechanisms driving initiation and progression. The initial model proposed by Fearon and Vogelstein posits it as a multi-hit neoplasia, originating from adenomatous-polyps induced by WNT activation, ultimately progressing to aggressiveness through p53 loss. Integrating human data with mouse genetics, we redefine this paradigm, highlighting pivotal roles of MYC, oncogenic URI and p53 degradation to initiate CRC. Early APC...
Irene Herranz-Montoya

CLAVATA signalling shapes barley inflorescence by controlling activity and determinacy of shoot meristem and rachilla

4 months 1 week ago
The large variety of inflorescence architectures evolved in grasses depends on shape, longevity and determinacy of meristems directing growth of the main and lateral axes. The CLAVATA pathway is known to regulate meristem size and inflorescence architecture in grasses. However, how individual meristem activities are determined and integrated to generate specific inflorescences is not yet understood. We found that activity of distinct meristems in the barley inflorescence is controlled by a...
Isaia Vardanega

Developing an indicator for community-level age-friendly communities: the Japan gerontological evaluation study

4 months 1 week ago
CONCLUSIONS: A valid and reliable 17-item community-level indicator was developed, aligning with the WHO framework and incorporating dementia-friendly elements. This indicator is a valuable tool for monitoring, evaluation, and inter-community comparisons, aiding the development of AFCs and DFCs in aging societies like Japan. Additionally, this indicator can be adapted for other high-income countries with similar socioeconomic backgrounds, healthcare systems, and community structures, providing a...
Satoko Fujihara

3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights Into MFN-2-Mediated Changes

4 months 1 week ago
Age-related skeletal muscle atrophy, known as sarcopenia, is characterized by loss of muscle mass, strength, endurance, and oxidative capacity. Although exercise has been shown to mitigate sarcopenia, the underlying governing mechanisms are poorly understood. Mitochondrial dysfunction is implicated in aging and sarcopenia; however, few studies explore how mitochondrial structure contributes to this dysfunction. In this study, we sought to understand how aging impacts mitochondrial...
Estevão Scudese

Deciphering Immunosenescence From Child to Frailty: Transcriptional Changes, Inflammation Dynamics, and Adaptive Immune Alterations

4 months 1 week ago
Aging induces significant alterations in the immune system, with immunosenescence contributing to age-related diseases. Peripheral blood mononuclear cells (PBMCs) offer a convenient and comprehensive snapshot of the body's immune status. In this study, we performed an integrated analysis of PBMCs using both bulk-cell and single-cell RNA-seq data, spanning from children to frail elderlies, to investigate age-related changes. We observed dynamic changes in the PBMC transcriptome during healthy...
Wenpu Lai

Altering metabolism programs cell identity via NAD<sup>+</sup>-dependent deacetylation

4 months 2 weeks ago
Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations in metabolism encode specific transcriptional instructions? Here, we show that forcing a metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the early mammalian blastocyst in cultures. This shift in cellular identity depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation...
Robert A Bone

Stromal lipid species dictate melanoma metastasis and tropism

4 months 2 weeks ago
Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are still incompletely understood. We show that abundant stromal lipids from young subcutaneous adipocytes, including phosphatidylcholines, are taken up by melanoma cells, where they upregulate melanoma PI3K-AKT signaling, fatty acid oxidation, oxidative phosphorylation (OXPHOS) leading to oxidative stress, resulting in decreased metastatic burden. High OXPHOS melanoma cells...
Shilpa Gurung

Cognitive frailty: a useful concept or a source of confusion? Insights from a survey of European geriatricians

4 months 2 weeks ago
CONCLUSIONS: There is no clear consensus opinion among geriatricians in Europe on the definition of 'cognitive frailty'. While there is some core support for the IANA-IAGG definition, it is not intuitive to those not already familiar with the term. The variance in the current understanding of cognitive frailty among geriatricians suggests the time is right for a meaningful debate on this issue. While there is ongoing, growing research on a shared pathophysiology between physical frailty and...
Suzanne Timmons

Inactivity is isolation: insights from a sedentary time intervention in assisted living

4 months 2 weeks ago
CONCLUSIONS: The natural communal setting of assisted living, along with supportive staff, presents a valuable opportunity to promote active aging, which is a complex interplay of social and movement behaviour. Our preliminary findings suggest that in addition to supporting individual behaviour change, a comprehensive approach that addresses the environment, social engagement, and staff engagement is needed in this setting. Future interventions should consider addressing each of these components...
Irmina Klicnik

Proactive end-of-life conversations in residential care homes: a qualitative interview study exploring residents' and family members' experiences

4 months 2 weeks ago
CONCLUSIONS: Proactive end-of-life conversations generated several beneficial outcomes for residents and family members, including those with cognitive decline. The study demonstrated that the conversations may strengthen person-centered care and family support in this context. Based on these findings, proactive end-of-life conversations have the potential for use by residential care home staff.
Åsa Mikaelsson

Vorinostat, a potential hormetin, extends lifespan and enhances stress resistance via the SKN-1 pathway in Caenorhabditis elegans

4 months 2 weeks ago
Vorinostat, a pan histone deacetylases (HDACs) inhibitor clinically approved for cutaneous T-cell lymphoma, exerts therapeutic effects by inducing tumor cell death and cycle arrest. Intriguingly, a previously unrecognized hormetic role of low-dose vorinostat in Caenorhabditis elegans. Subtoxic concentrations of vorinostat (1 μM) significantly extended lifespan, enhanced healthspan, and improved resistance to oxidative and heat stress, while ameliorating Aβ-induced paralysis. qPCR analysis...
Shuai Huang

Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice

4 months 2 weeks ago
Microglia are parenchymal brain macrophages that are established during embryogenesis and form a self-containing cellular compartment that resists seeding with cells derived from adult definitive hematopoiesis. We report that monocyte-derived macrophages (MoMΦs) accumulate in the brain of aging mice with distinct topologies, including the nigrostriatum and medulla but not the frontal cortex. Parenchymal MoMΦs adopt bona fide microglia morphology and expression profiles. Due to their...
Jung-Seok Kim
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