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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...

Blood biomarkers of Alzheimer's disease (AD) are promising for dementia prediction, but their association with progression across intermediate stages of cognitive decline in the general population remains unclear. We followed 2148 dementia-free individuals from a Swedish population-based cohort for up to 16 years. Associations between baseline AD blood biomarkers and transitions between normal cognition, mild cognitive impairment (MCI), and dementia were examined. Lower amyloid-β42/40 ratio and...

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...

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...