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DMTF1 up-regulation rescues proliferation defect of telomere dysfunctional neural stem cells via the SWI/SNF-E2F axis

2 months 4 weeks ago
Impaired neural stem cell (NSC) proliferation/activation is associated with brain aging, but the underlying mechanisms remain poorly understood. Here, we unexpectedly find that DMTF1, a transcription factor that regulates the Arf/p53 axis in cancer, is down-regulated in the NSCs of a premature aging model driven by telomerase deficiency. DMTF1 up-regulation was able to rescue the impaired proliferation of telomere dysfunctional NSCs. Mechanistically, DMTF1 regulates the transcription of Arid2...
Yajing Liang

Perturbation of NAD(P)H metabolism with the LbNOX xenotopic tool extends lifespan and mitigates age-related changes

2 months 4 weeks ago
Aging involves widespread metabolic dysregulation, including a decline in total nicotinamide adenine dinucleotide (NAD) levels. While NAD precursor supplementation elevates total NAD levels, it does not reveal tissue-specific effects of an altered NADH [reduced form of NAD^(+) (oxidized NAD)]/NAD^(+) balance. To address this, we generated transgenic Drosophila expressing the genetically encoded xenotopic enzyme LbNOX, which converts NADH to NAD^(+). LbNOX expression modulated both NAD(H) and...
Shweta Yadav

Systemic LINE-1 RNA in Plasma Extracellular Vesicles Drives Neuroinflammation and Cognitive Dysfunction via cGAS-STING Pathway in Aging

2 months 4 weeks ago
Aging is characterized by systemic inflammation and progressive cognitive decline, yet the molecular pathways linking peripheral aging signals to central nervous system dysfunction remain elusive. Here, we identify plasma extracellular vesicle (EV)-derived long interspersed nuclear element-1 (LINE-1) RNA as a potent systemic aging factor mediating neuroinflammation and cognitive impairment in humans and mice. Plasma EV LINE-1 RNA levels markedly increase with age and strongly correlate with...
Shuyi Yu

Cancer cell death: Cell-autonomous and immunogenic dimensions

3 months ago
Regulated cell death (RCD) shapes neoplastic transformation, tumor progression, and response to treatment. While apoptosis was long viewed as the only RCD variant, additional modalities, including necroptosis, pyroptosis, and ferroptosis, have been characterized. These interconnected pathways operate in a context-dependent manner to influence the dynamic interplay between malignant and non-malignant cells that governs disease progression or regression, both naturally and during therapy. Major...
Lorenzo Galluzzi

The skeletal muscle function deficit: From an operational definition to clinic results from the InCHIANTI longitudinal study

3 months ago
Age-related muscle dysfunction is a major contributor to disability, frailty, and poor clinical outcomes in older adults. Skeletal Muscle Function Deficit (SMFD) framework integrates multiple domains as: muscle mass, muscle density, strength, and power to capture a broader spectrum of age-related muscle dysfunction. The primary aims of these analyses are to develop and validate a composite SMFD score and evaluate its association with key geriatric outcome. This study used data from the InCHIANTI...
Angelo Di Iorio

Longevity of cardiac and skeletal muscle proteins is dependent on tissue and subcellular compartmentation patterns

3 months ago
Myocytes are exceptionally long-lived cells that must maintain proteome integrity over decades while adjusting for changes in functional output and metabolic demand. We used in vivo stable isotope labeling combined with mass spectrometry proteomics and correlated multi-isotope imaging mass spectrometry to quantify and visualize protein turnover across cardiac, fast-twitch, and slow-twitch skeletal muscles, creating a resource of hundreds of individual protein turnover rates from each tissue. We...
Jack Gugel

Immunosuppressive macrophages determine the effect of cellular senescence on tumor progression

3 months ago
Cells terminally arrested in the cell cycle that exhibit a distinct secretory phenotype are referred to as senescent. These cells play a complex role during tumor progression; they can inhibit or promote tumor growth depending on disease stage. We developed a mouse model that allows monitoring and selective elimination of cells expressing high levels of the cyclin-dependent kinase inhibitor p16 and interleukin-6. These mice, termed SuSe (suicidal senescence), were crossed with the mouse mammary...
Marta Lalinde-Gutiérrez