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Mothers with obesity and gestational diabetes did not induce brain pathologies or premature brain aging in their adolescent and early adult offspring in rats

5 months ago
This study investigated the effect of a medium high-fat diet (HFD)-induced maternal obesity and gestational diabetes mellitus (GDM) on rat offspring to verify the hypothesis that maternal obesity and GDM cause brain pathologies and premature brain aging in the prefrontal cortex and hippocampus of the adolescent and early adult offspring. Maternal obesity and GDM were generated by a medium HFD and HFD combined with streptozotocin, respectively. Metabolic parameters were used to confirm the...
Huatuo Huang

Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis: Role of Immunosenescence

5 months ago
The onset of multiple sclerosis (MS) in older individuals correlates with a higher risk of developing primary progressive MS, faster progression to secondary progressive MS, and increased disability accumulation. This phenomenon can be related to age-related changes in the immune system: with age, the immune system undergoes a process called immunosenescence, characterized by a decline in the function of both the innate and adaptive immune responses. This decline can lead to a decreased ability...
María Dema

A central role for acetylcholine in entorhinal cortex function and dysfunction with age in humans and mice

5 months ago
Structural and functional changes in the entorhinal cortex (EC) are among the earliest signs of cognitive aging. Here, we ask whether a compromised cholinergic system influences early EC impairments and plays a primary role in EC cognition. We evaluated the relationship between loss of integrity of cholinergic inputs to the EC and cognitive deficits in otherwise healthy humans and mice. Using in vivo imaging (PET/MRI) in older humans and high-resolution imaging in wild-type mice and mice with...
Mala R Ananth

Loss of endothelial CD2AP causes sex-dependent cerebrovascular dysfunction

5 months ago
Polymorphisms in CD2-associated protein (CD2AP) predispose to Alzheimer's disease (AD), but the underlying mechanisms remain unknown. Here, we show that loss of CD2AP in cerebral blood vessels is associated with cognitive decline in AD subjects and that genetic downregulation of CD2AP in brain vascular endothelial cells impairs memory function in male mice. Animals with reduced brain endothelial CD2AP display altered blood flow regulation at rest and during neurovascular coupling, defects in...
Milène Vandal

Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage

5 months ago
Thymic injury associated with disease or cancer treatment reduces T cell production and makes patients more vulnerable to infections and cancers. Here, we examined the role of regulatory T (Treg) cells on thymic regeneration. Treg cell frequencies increased in the thymus in various acute injury models. Depletion of Treg cells impaired thymic regeneration, impacting both the thymocyte compartment and the stromal cell compartment; adoptive transfer of Treg cells enhanced regeneration. Expansion of...
Andri L Lemarquis

Focused ultrasound widely broadens AAV-delivered Cas9 distribution and activity

5 months ago
Because children have little temporal exposure to environment and aging, most pediatric neurological diseases are inherent, i.e. genetic. Since postnatal neurons and astrocytes are mostly non-replicating, gene therapy and genome editing present enormous promise in child neurology. Unlike in other organs, which are highly permissive to adeno-associated viruses (AAV), the mature blood-brain barrier (BBB) greatly limits circulating AAV distribution to the brain. Intrathecal administration improves...
Emrah Gumusgoz

A central role for acetylcholine in entorhinal cortex function and dysfunction with age in humans and mice

5 months ago
Structural and functional changes in the entorhinal cortex (EC) are among the earliest signs of cognitive aging. Here, we ask whether a compromised cholinergic system influences early EC impairments and plays a primary role in EC cognition. We evaluated the relationship between loss of integrity of cholinergic inputs to the EC and cognitive deficits in otherwise healthy humans and mice. Using in vivo imaging (PET/MRI) in older humans and high-resolution imaging in wild-type mice and mice with...
Mala R Ananth

Association between occupational complexity and cognitive function in older adults from Brazil and Mexico

5 months ago
More complex occupations during adulthood may be associated with better cognition in later life. We used data from the Brazilian Longitudinal Study of Aging (ELSI) and the Mexican Health and Aging Study (MHAS) to investigate the association between occupational complexity and cognitive function. Using a regression-based approach, participants were classified as cognitively impaired or not. Occupation was categorized into four levels using the 2008 International Standard of Classification of...
Natalia Gomes Goncalves

Bidirectional relationship between epigenetic age and stroke, dementia, and late-life depression

5 months ago
Chronological age is an imperfect estimate of molecular aging. Epigenetic age, derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. We examine the bidirectional relationship between epigenetic age and brain health events (stroke, dementia, late-life depression) using data from 4,018 participants. Participants with a prior brain health event are 4% epigenetically older (β = 0.04, SE = 0.01), indicating these conditions are associated...
Cyprien A Rivier

Using CT imaging to identify sarcopenia as a risk factor for severe falls in older adults

5 months ago
CONCLUSIONS: These results underscore the importance of addressing sarcopenia and related risk factors, including malnutrition, in the management and prevention of severe falls in the elderly population. Body composition analyzed in CT-scans could add value in this risk assessment. This analysis could be conducted opportunistically during CT scans performed for other purposes.
Nadja Fries

Uncovering dark mass in population proteomics: Pan-analysis of single amino acid polymorphism relevant to cognition and aging

5 months ago
Human proteome data across populations have been analyzed extensively to reveal protein quantitative associations with physiological or pathological states, while the single amino acid polymorphism (SAP) has been rarely investigated. In this work, we introduce a pan-SAP workflow that relies on pan-database searching independent of individual genome sequencing. Using ten cohorts comprising 2,004 individuals related to cognition disorder and aging, we quantify the SAP sites in key proteins, such...
Xiaojing Gao

Uncovering dark mass in population proteomics: Pan-analysis of single amino acid polymorphism relevant to cognition and aging

5 months ago
Human proteome data across populations have been analyzed extensively to reveal protein quantitative associations with physiological or pathological states, while the single amino acid polymorphism (SAP) has been rarely investigated. In this work, we introduce a pan-SAP workflow that relies on pan-database searching independent of individual genome sequencing. Using ten cohorts comprising 2,004 individuals related to cognition disorder and aging, we quantify the SAP sites in key proteins, such...
Xiaojing Gao

Strides towards healthy longevity: Harnessing the power of sports and elements of Kathak, an Indian classical dance form through social participation to combat cognitive frailty among older adults

5 months ago
Aging brings with it many health issues that can make life challenging. As much of the attention is given to non-communicable diseases, there are others which are slowly becoming a matter of great concern. One such issue is cognitive frailty, which is a high risk factor for dementia, falls, fractures and hospitalization. Though not yet declared a public health concern, it deserves early detection and prevention strategies. As it is reversible if treated on time, there is a need to look into its...
Abhijeet Singh Dewari

Cognition Assessment With ICOPE-Monitor: Identifying Candidates for Novel Therapies

5 months ago
CONCLUSION AND IMPLICATIONS: CogStep1 demonstrated good sensitivity and PPV to identify objective cognitive impairment among older people referred to a memory clinic. Achieving excellent sensitivity and specificity values is challenging for a very short test. However, CogStep1 proved useful for risk-stratifying patients who can benefit from further cognitive assessment, biomarker measurements, and therapeutic management, especially in the context of new anti-amyloid therapies.
Emmanuel Gonzalez-Bautista

Upregulation of LXRbeta/ABCA1 pathway alleviates cochlear hair cell senescence of C57BL/6 J mice via reducing lipid droplet accumulation

5 months ago
Senescence and loss of cochlear hair cells is an important pathologic basis of age-related hearing loss. Lipid droplet accumulation has previously been shown to play an important role in neurodegeneration; however, its role in age-related hearing loss has not yet been investigated. LXRβ/ABCA1 is a key pathway that regulates lipid metabolism, while its dysfunction can cause abnormal accumulation of lipid droplets in neurons, leading to neurodegeneration. In this study, we found that decreased...
Dongye Guo