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Scientists have uncovered why two seemingly opposite ways of targeting the same brain receptor can both promote weight loss. In mice, activating the GIP receptor in the brainstem reduced appetite, while blocking it in the hypothalamus removed a kind of “brake” on fullness signals. The discovery helps explain why very different obesity drugs can achieve similar results and suggests that carefully combining GIP-targeting treatments with GLP-1 drugs like those related to Wegovy and Ozempic could produce stronger effects.

CONCLUSIONS: The flexible Choose Home model successfully fills a gap in the home and community-based care continuum by providing time-limited, high-intensity case management to rapidly stabilize multicomplex older Veterans. This sustainable, provider-led interprofessional approach offers a scalable strategy to support aging in place and reduce costly institutional care.

One of the defining phenotypes of a senescent cell is the senescence-associated secretory phenotype (SASP), which can propagate senescence in neighboring cells both in vitro and in vivo. Importantly, this paracrine spreading of senescence can act in a cell non-autonomous manner, influencing neighboring cell populations and contributing to immune cell recruitment. As cellular senescence has recently been linked to both age-related neurodegenerative phenotypes and local inflammation and is more...

Scientists have discovered that the aging human brain may be far less isolated from the rest of the body than once believed. Stanford researchers found that large numbers of immune cells from the blood begin entering the brain as early as middle age, where they can transform into microglia, the brain’s specialized immune cells. The finding overturns a long-standing assumption that these cells remain largely separate from the body’s immune system throughout life.

Simply choosing the stairs could have surprisingly big benefits for your heart and longevity. A large analysis involving more than 480,000 people found that regular stair climbers were 39% less likely to die from cardiovascular disease and 24% less likely to die from any cause than people who rarely took the stairs. They also had lower risks of heart attack, stroke, and heart failure.

A surprising stress-related signal may help the brain repair itself after injury. Researchers found that myelin-producing precursor cells rapidly release the stress hormone CRH near damaged brain tissue, helping control how those cells mature and rebuild protective nerve insulation. The same system also influences brain development and the thickness of myelin later in life. The findings could offer new clues about how early-life stress contributes to psychiatric disorders.

Women who used estrogen-only hormone therapy later in life were less likely to develop dementia and showed fewer signs of Alzheimer’s disease in their brains, according to a large study of more than 21,000 participants. Hormone therapy use was linked to 39% lower odds of a dementia diagnosis and 35% lower odds of Alzheimer’s-related brain changes at autopsy, including amyloid plaques and tau tangles. Biomarker tests also suggested less amyloid buildup among hormone therapy users.

Mitochondria are essential metabolic and signalling hubs exposed to stress, and mitochondrial damage is highly detrimental to the cell. Mitophagy - the autophagy of mitochondria - is a key mechanism that maintains both mitochondrial integrity and metabolic flexibility. Mitophagy occurs via multiple pathways that either involve activation of PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin-protein ligase Parkin, or are independent of PINK1 and Parkin. Recessive mutations in PINK1 and PKRN (the...

We developed a high-content screening to investigate how Alzheimer's disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently disrupted dendritic morphology and synaptic function. In human neuronal cultures (hNCs), PLCG2 downregulation also impaired synaptic function and increased amyloid-β (Aβ) levels and Tau phosphorylation. Very rare PLCG2...

Aging is the primary risk factor for chronic disease and is characterized by profound structural and architectural remodeling of human tissues. Here, we present a comprehensive assessment of these changes using 25,712 whole-slide histopathological images from 40 tissue types across 983 individuals in the Genotype-Tissue Expression cohort. By leveraging deep learning, we quantified nuanced morphological alterations to develop 'tissue clocks', predictors of biological age that reflect tissue...

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Understanding how brain connectivity reorganizes with age is essential for characterizing healthy aging. While static functional connectivity (sFC) has revealed broad age-related shifts in network segregation and integration, recent work underscores the need to examine how these patterns dynamically fluctuate over time to better understand cognitive decline and resilience in aging. The present resting-state fMRI study was conducted to enhance comprehension of the temporal variability and...

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by de novo LMNA mutations. Patients develop severe systemic symptoms limiting life quality and ultimately causing death from cardiovascular events. Despite extensive research, treatment options remain limited. Here, we investigated the role of long non-coding RNAs (lncRNAs) in the development of vascular pathology in HGPS. We analyzed an available single-cell RNA sequencing dataset from aortic arch cells of...

CONCLUSION: While the vast majority of the homebound population is frail or pre-frail, a considerable portion are not frail. Efforts to manage high-need, high-cost populations such as homebound older adults must account for the heterogeneity of the population with efforts to better understand the non-frail subpopulation and target interventions tailored to their needs with the goal of potentially reversing their homebound status.

Ovarian aging leads to infertility, endocrine dysregulation and increased chronic disease risk, yet there are currently no approved therapies to delay ovarian aging. Physical activity (PA) is a crucial lifestyle factor for human health and antiaging, but its effects and mechanisms on ovarian aging remain unclear. Here we show, through a cross-sectional analysis of 152,435 participants in the UK Biobank, that lower PA levels were observed among postmenopausal persons when compared to...

Aging is the primary risk factor for chronic disease and is characterized by profound structural and architectural remodeling of human tissues. Here, we present a comprehensive assessment of these changes using 25,712 whole-slide histopathological images from 40 tissue types across 983 individuals in the Genotype-Tissue Expression cohort. By leveraging deep learning, we quantified nuanced morphological alterations to develop 'tissue clocks', predictors of biological age that reflect tissue...

Spontaneous intracerebral hemorrhage (ICH) is a highly lethal and disabling form of stroke, in which hematoma expansion (HE) is a major and potentially modifiable determinant of early neurological deterioration and poor functional outcome. Computed tomography (CT) remains the first-line imaging modality for acute ICH and provides essential information for early HE risk stratification. However, current evidence is dispersed across conventional CT signs, composite scores, radiomics, machine...

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular...

CONCLUSIONS: Exercise improves balance, but modality choice should consider balance domain. Current estimates were most favourable for perturbation training in overall and static balance under supervision, sensory training at home, Tai Chi in global balance, Pilates in dynamic balance, and agility stepping or aquatic exercise in proactive balance. These estimates do not establish superiority. Dose should reflect task-specific challenge, safety and feasibility, because METs capture metabolic cost...

CONCLUSION: Moderate levels of green and blue spaces were associated with lower levels of biological aging. Nonlinear associations were stronger in socially vulnerable groups, suggesting that equitable nature-based planning could be a strategic public health intervention to promote healthy aging.