Aging & Longevity
Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders
The human brain is one of the most metabolically active tissues in the body, due in large part to the activity of trillions of synaptic connections. Under normal conditions, macroautophagy/autophagy at the synapse plays a crucial role in synaptic pruning and plasticity, which occurs physiologically in the absence of disease- or aging-related stressors. Disruption of autophagy has profound effects on neuron development, structure, function, and survival. Neurons are dependent upon maintaining...
Spatiotemporal Crosstalk Between Oocyte and the Microenvironment Governs Preovulatory Follicle Aging
Preovulatory follicle aging is the period between formation and ovulation of a mature follicle. Previous studies had shown that mammalian preovulatory follicle aging is associated with chromosomal abnormalities and developmental defects such as decreased implantation, increased malformation and mortality and lower embryonic weight. Our understanding of the molecular events governing this process has been hampered by the difficulty in accessing them in vivo under natural conditions. We...
The Muscle-Brain Axis in Type 2 Diabetes: Molecular Pathways Linking Sarcopenia and Cognitive Decline
Type 2 diabetes mellitus (T2DM) is increasingly recognized as a shared pathological substrate for both sarcopenia and cognitive decline, particularly Alzheimer's disease (AD). This review synthesizes current evidence on the converging molecular pathways linking insulin resistance, hyperglycaemia, mitochondrial dysfunction, oxidative stress, and chronic inflammation to muscle wasting and neurodegeneration. Central to this interplay is the muscle-brain axis, a bidirectional communication network...
Disruption of Krox20-Notch1 signaling blocks meibomian gland development and homeostasis leading to dry eye disease
Meibomian gland dysfunction (MGD) is the leading cause of Dry Eye Disease (DED), accounting for approximately 90% of DED cases worldwide. The transcription factor KROX20 has been shown to mark stem cells that play a critical role in Meibomian gland (MG) development and homeostasis, however, the molecular mechanisms underlying these processes are not well understood. In this report, we used multiple Krox20 lineage tracing and ablation studies to investigate lineage commitment during MG...
Cognition and brain network connectivity in timed up & go performance
Gait performance depends on numerous aspects of brain functioning that are also relevant to key cognitive processes throughout the lifespan. The Timed Up and Go (TUG) test has been shown to be a reliable tool for assessing age-related mobility changes and risk of falls in older adults. This study aimed to predict TUG performance using motor-cognitive inter-network connectivity, cognitive performance and socio-demographics. 189 participants without cognitive impairment were included. Mobility was...
Mechanisms governing poly(A)-tail-length specificity of the human PAN2-PAN3 deadenylase complex
The lifespan of most eukaryotic mRNAs is modulated by the gradual shortening of the poly(A) tail and removal of the associated poly(A)-binding protein. The human PAN2-PAN3 complex catalyzes initial deadenylation by shortening long poly(A) tails associated with PABPC1. Both PAN2-PAN3 and PABPC1 are evolutionarily conserved from fungi to humans. How the human complex has adapted to recognize and act on longer poly(A) tails characteristic of mammalian mRNAs remains unclear. Here, we report a method...
Astrocytic Sox9 overexpression in Alzheimer's disease mouse models promotes Aβ plaque phagocytosis and preserves cognitive function
Astrocytes play essential roles in the brain, and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, knowledge of how astrocytes contribute to disease pathogenesis is incomplete; accordingly, harnessing their biology toward therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context-specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer's disease...
The Dubousset functional test: a reliable and validated physical function and balance assessment tool for older Chinese adults
CONCLUSION: The Dubousset Functional Test demonstrated relatively good psychometric properties for geriatric functional assessment.
Factors influencing health service utilisation among older adults in the Tamale metropolis: a cross-sectional study based on Andersen's behavioural model
CONCLUSIONS: Health service utilisation among older adults in Tamale was associated with a combination of predisposing, enabling, and need factors. While insurance coverage was high and contributed to health service utilisation, self-employment and living more than 4 km from a facility were major barriers. Community-based outreach, including mobile health clinics or targeted home-based care, may be a cost-effective approach to improving older adults’ access to and utilisation of health services.
Exploring patient-centered care delivery in outpatient settings for older adults: a scoping review and recommendations for implementation in countries with low and middle income
CONCLUSIONS: This review highlights the potential of PCC in enhancing the quality of care for older adults in outpatient settings. Building on our findings, a phased approach focusing on older adults with multimorbidity is recommended for LMICs like Iran, with an emphasis on integrating both primary and specialized care. Our proposed seven-dimensional PCC model includes access to care, proactive care, patient empowerment, integration into care pathways, a whole-person approach, coordinated care,...
Perceived stress and health-related quality of life according to hearing status in elderly people: a cross-sectional study
CONCLUSION: BHL was associated with increased perceived stress and poorer HRQoL, whereas UHL did not differ significantly from the reference group in perceived stress but was associated with poorer physical and mental HRQoL. These findings highlight the importance of early identification and intervention for hearing loss to improve health-related outcomes in elderly people.
The impact of frailty and fear of falling on health-related quality of life in older adults with osteoporosis: a cross-sectional study
CONCLUSION: Frailty and fear of falling exert significant and interactive effects on health-related quality of life in older adults with osteoporosis. The findings underscore the need for comprehensive, multidimensional interventions targeting both frailty and fear of falling to improve health-related quality of life and promote successful aging in this vulnerable population.
Immunoglobulin G and Aging: Biological Functions and Its Crosstalk with the Gut Microbiota
Aging is characterized by a progressive decline in physiological integrity, often accompanied by chronic inflammation and immune dysregulation. Immunoglobulin G (IgG), a key effector of humoral immunity, undergoes substantial structural and functional remodeling with age, particularly through changes in its glycosylation profile. These modifications shift IgG toward a proinflammatory state, linking it to inflammaging and multiple age-related diseases. This review synthesizes recent advances in...
Nicotinamide riboside supplementation restores microglial health and improves cognition in aged male mice
Cognitive impairment affects 1 in 6 individuals over 60, with over 75 million projected by 2030. Age-related changes in microglial function and declining nicotinamide adenine dinucleotide (NAD^(+)) levels may contribute to cognitive decline. Although nicotinamide riboside (NR) supplementation can restore NAD^(+) levels in aged mice, its effects on microglial phenotype and cognition during normal aging remain unclear. We assessed cognitive function, neuroinflammation, and microglial gene...
Effects of aging on transmission from Ia afferents to alpha-motoneurons and presynaptic mechanisms across muscle lengths and contraction types
Presynaptic inhibition of Ia afferents, particularly via primary afferent depolarization (PAD), plays a crucial role in modulating transmission from Ia afferents to α-motoneurons according to task demands. In young adults, PAD is enhanced during eccentric contractions and at longer muscle lengths, supporting adaptable motor control. However, aging is associated with reduced muscle spindle sensitivity, which may impair the regulation of presynaptic inhibition via PAD. This study investigated...
Disruption of Rab9-dependent mitophagy contributes to menopause-induced sarcopenia
CONCLUSION: This study demonstrates that estrogen deficiency impairs mitophagy originated from Rab9-dependent alternative autophagy, leading to mitochondrial dysfunction and sarcopenia, while enhancement of Rab9 restores mitochondrial quality control and muscle function. These results identify Rab9-dependent mitophagy as a potential therapeutic target for postmenopausal sarcopenia.
DNA Methylation Signatures of Systemic Inflammation Are Associated With Brain Volume, Cognitive Trajectories, and Long-Term Dementia Risk
C-reactive protein (CRP) and growth differentiation factor 15 (GDF15) are important markers of inflammation associated with brain health. Compared to plasma, DNA methylation (DNAm) measures of CRP and GDF15 may provide stable epigenetic measures of chronic exposure to inflammation and could therefore be robustly predictive of inflammation-related brain aging and neurodegeneration. We leveraged a subsample of Baltimore Longitudinal Study of Aging (BLSA) participants with DNAm/plasma data and...
Dynamical analysis of a model of BCL-2-dependent cellular decision making
The BCL-2 protein family governs critical cell-fate decisions between survival, senescence, and apoptosis, yet the dynamical principles underlying these choices remain poorly understood. Here, we integrate mathematical modeling, bifurcation analysis, and stochastic simulations to dissect how BCL-2 network architecture encodes multistability and fate plasticity. Our coarse-grained model reveals tristable regimes requiring cooperative BH3-only and anti-apoptotic BCL-2 interactions, with stochastic...
Integrative gene-metabolite network analysis of GLP-1 receptor agonists and related incretin pathways in cardiometabolic health
Glucagon-like peptide-1 (GLP-1) is a hormone known for its critical functions in managing blood sugar and offering cardiovascular benefits. Our study focuses on Glucagon Like Peptide 1 Receptor (GLP1R) agonists that act beyond glycemic control in cardiovascular and metabolic health. A comprehensive bioinformatic analysis was conducted, incorporating GLP1R, Gastric Inhibitory Polypeptide Receptor (GIPR), Gastric Inhibitory Polypeptide (GIP) and glucagon receptor (GCGR) to assess the effects of...
Colorectal cancer screening, incidence, and mortality among aging veterans in the U.S. Department of Veterans Affairs healthcare system by housing status
The objectives of this study are to examine colorectal cancer (CRC) screening, incidence, and mortality among veterans 45 to 75 years who are enrolled in the U.S. Department of Veterans Affairs (VA) healthcare system by housing instability or homelessness (HUH) and determine whether receiving primary care via Homeless Patient Aligned Care Teams (HPACTs) affects CRC screening, incidence, and mortality among veterans experiencing HUH. A retrospective cohort study was conducted among > 3,000,000...
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