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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...

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...

Spatial disorientation is emerging as an early cognitive biomarker of dementia, but the underlying neural mechanisms remain undefined. The anterodorsal nucleus of the thalamus (ADn) exhibits early and selective vulnerability to pathological misfolded forms of tau, a major hallmark of Alzheimer's disease. As the ADn contains a high density of head direction (HD) cells, we hypothesized that ptau disrupts HD cell activity, promoting spatial disorientation. To test this, we virally expressed human...

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...

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...

Sex-biased differences in Alzheimer's disease (AD) are well documented, but the mechanisms underlying increased vulnerability in postmenopausal women remain unclear. This study aimed to model the effects of perimenopausal hormonal fluctuations on AD pathophysiology. Using a VCD-induced accelerated ovarian failure model in young female C57BL/6 J and 3xTg mice, we simulated a perimenopausal state with hormonal changes characterised by elevated oestradiol levels and reduced progesterone levels....

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...

CONCLUSION: The Dubousset Functional Test demonstrated relatively good psychometric properties for geriatric functional assessment.

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.

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,...

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.

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.

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...

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...

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...

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.

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...

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...

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...

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...