Aging & Longevity

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...

CONCLUSION: Our findings reveal that elderly individuals showed larger MNCSA, whether or not they have diabetes, compared to young group. These findings suggest that aging is a dominant factor in the increase in MNCSA and that T2D may exacerbate it We propose that changes in MNCSA associated with diabetes could be part of the normal aging process, rather than representing an independent pathology.

CONCLUSION: Loneliness significantly explains the sarcopenia-mental health relationship, with men exhibiting stronger indirect pathways via loneliness. This highlights the need for integrated interventions targeting sarcopenia (e.g., resistance training) and loneliness (e.g., group-based social activities), tailored to sex-specific mechanisms. Scaling such approaches is urgent for the aging society, with highly prevalent sarcopenia and mental health problems among older adults.

CONCLUSION: The model generated for this study showed that adults with older age, diabetes, greater dependency in activities of daily living, and decreased functional status were more frail and that genetic markers conferred a greater risk of presenting frailty.

To further understand whether childhood maltreatment (CM) is associated with indicators of accelerated cognitive aging, this study investigated whether CM moderated the relationship of age with gray matter volume (GMV) and executive functions among community adults aged 21-55. Participants (N = 225) underwent MRI scanning, and a composite measure of executive functions was computed across measures of inhibitory control, switching, and working memory. To interpret interactions, we created high...

Accumulation of senescent cells is a key contributor to multiple diseases across the lifespan, including metabolic dysfunction. We previously demonstrated that elimination of senescent cells using senolytic drugs alleviates obesity-induced metabolic dysfunction. However, the contribution of senescent endothelial cells to metabolic disorders remains elusive. Hence, we crossed mice that allow selective elimination of senescent cells (p16^(Ink4a)-LOX-ATTAC mice) with Tie2-Cre mice...

Menopause is a hallmark of women's aging and is frequently portrayed as a medical issue. It also encompasses social and biological aspects often neglected and not well-understood, leaving women with insufficient support and attention. With the decline in estrogen levels, starting years before menopause is fully established, women experience various physical symptoms, and the risk of many age-related diseases increases sharply soon after these hormonal changes occur. Notably, these hormonal...

CONCLUSIONS AND IMPLICATIONS: High-risk prescribing is common in those living with dementia and varies by sociodemographic factors. Regular, targeted medication reviews are needed to ensure quality use of medicines in this population.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, leading to fatal muscle paralysis. Familial forms of ALS (fALS) account for approximately 10% of cases. Alterations of mitochondrial functions have been proposed to contribute to disease pathogenesis. Here, we employed a direct conversion (DC) technique to generate induced motor neurons (iMN) from skin fibroblasts to investigate mitochondrial phenotypes in a patient-derived disease relevant cell...

Spermine, a pivotal player in biomolecular condensation and diverse cellular processes, has emerged as a focus of investigation in aging, neurodegeneration, and other diseases. Despite its significance, the mechanistic details of spermine remain incompletely understood. Here, we describe the distinct modulation by spermine on Alzheimer's Tau and Parkinson's α-synuclein, elucidating their condensation behaviors in vitro and in vivo. Using biophysical techniques including time-resolved SAXS and...

Loss of Fibronectin (FN) from the skeletal muscle stem cell (MuSC) niche represents a root cause of regenerative failure in aging. While FN has pleiotropic functions during healthy skeletal muscle regeneration, it remains unclear how aging affects its spatiotemporal specificity for MuSCs. Here, we demonstrate that activated MuSCs secrete an autoregulatory FN splice variant containing the EDB extra domain (EDB(+) FN), which is not expressed by accessory cells in the niche. EDB(+) FN splicing in...

Brain atrophy is a key factor behind episodic memory loss in aging, but the nature and ubiquity of this relationship remains poorly understood. This study leverages 13 longitudinal datasets, including 3737 cognitively healthy adults (10,343 MRI scans; 13,460 memory assessments), to determine whether brain change-memory change associations are more pronounced with age and genetic risk for Alzheimer's Disease. Both factors are associated with accelerated brain decline, yet it remains unclear...

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Cognitive impairment is associated with perturbations of fine-tuned neuroimmune interactions. At the molecular level, alterations in cellular metabolism can compromise brain function, driving structural damage and cognitive deficits. In this Review, we focus on the bidirectional interactions between microglia, the brain-resident immune cells and neurons to dissect the metabolic determinants of brain resilience and cognition. We first outline these metabolic pathways during development and adult...

Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using RNAseq analysis of young, isogenic, subpopulations of Caenorhabditis elegans selected solely on the basis of the splicing pattern of an in vivo minigene reporter that is predictive of future life expectancy, we find a strong correlation in young animals between...

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