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MAPL regulates gasdermin-mediated release of mtDNA from lysosomes to drive pyroptotic cell death

2 months 1 week ago
Mitochondrial control of cell death is of central importance to disease mechanisms from cancer to neurodegeneration. Mitochondrial anchored protein ligase (MAPL) is an outer mitochondrial membrane small ubiquitin-like modifier ligase that is a key determinant of cell survival, yet how MAPL controls the fate of this process remains unclear. Combining genome-wide functional genetic screening and cell biological approaches, we found that MAPL induces pyroptosis through an inflammatory pathway...
Mai Nguyen

The interactome era: Integrating RNA-seq, proteomics, and network biology to decode cellular senescence

2 months 1 week ago
Cellular senescence is a dynamic state in which cells permanently withdraw from the cell cycle while continuing to reshape their internal and external environment. It is characterized by persistent DNA damage responses, chromatin reorganization, and the secretion of a complex mixture of cytokines and proteases collectively known as the senescence-associated secretory phenotype (SASP). Transcriptomic and proteomic studies have defined key markers, including CDKN2A, CDKN1A, TP53, and SASP factors,...
Mohd Shahzaib

Effects of lifetime supplementation with ubiquinol 10 on the lifespan and progression of aging in female C57BL/6 mice

2 months 1 week ago
Supplementation with ubiquinol 10 has been shown to improve the health of experimental animals and elderly individuals. The present study investigated the effects of lifetime supplementation with ubiquinol 10 on the progression of aging and lifespan in C57BL/6 mice, a standard strain for biomedical and aging research. A diet containing ubiquinol 10 (0.3 % w/w) and a control diet were fed to female C57BL/6J mice from 8 weeks of age until death, and the progression of senescence, lifespan, and...
Yuichi Igarashi

Sex differences in healthy brain aging are unlikely to explain higher Alzheimer's disease prevalence in women

2 months 1 week ago
As Alzheimer's disease (AD) is diagnosed more frequently in women, understanding the role of sex has become a key priority in AD research. However, despite aging being the primary risk factor for AD, it remains unclear whether men and women differ in the extent of brain decline with age. Using 12,638 longitudinal brain MRIs from 4,726 participants aged 17 to 95 y across 14 cohorts, we examined sex differences in structural brain changes over time, controlling for differences in head size. Men...
Anne Ravndal

Precise gene editing of pathogenic Lamin A mutations corrects cardiac disease

2 months 1 week ago
Mutations in the Lamin A (LMNA) gene, which encodes the Lamin A and C proteins, cause severe human diseases collectively known as laminopathies. These conditions are often devastating and lack effective therapies. In this study, we developed precise base editing (BE) strategies targeting the human LMNA gene variants L35P and R249Q, which cause congenital muscular dystrophy (CMD) and dilated cardiomyopathy with conduction defects (DCM-CD), respectively. Induced pluripotent stem cell-derived...
Xurde M Caravia

Sex differences in healthy brain aging are unlikely to explain higher Alzheimer's disease prevalence in women

2 months 1 week ago
As Alzheimer's disease (AD) is diagnosed more frequently in women, understanding the role of sex has become a key priority in AD research. However, despite aging being the primary risk factor for AD, it remains unclear whether men and women differ in the extent of brain decline with age. Using 12,638 longitudinal brain MRIs from 4,726 participants aged 17 to 95 y across 14 cohorts, we examined sex differences in structural brain changes over time, controlling for differences in head size. Men...
Anne Ravndal

Post-reproductive lifespan in wild mountain gorillas

2 months 1 week ago
Animals can typically maximize their fitness by reproducing throughout adulthood. Yet, in a handful of species, females cease reproduction long before death, highlighting an apparent evolutionary paradox. We used over three decades of life-history and behavioral data to examine the prevalence of postreproductive lifespan in wild mountain gorillas (Gorilla beringei beringei). Almost one third of females in our study population (7/25) have been "postreproductive" according to a commonly used...
Nikolaos Smit