Aging & Longevity

Targeting the redox system for cardiovascular regeneration in aging

2 weeks 4 days ago
Cardiovascular aging presents a formidable challenge, as the aging process can lead to reduced cardiac function and heightened susceptibility to cardiovascular diseases. Consequently, there is an escalating, unmet medical need for innovative and effective cardiovascular regeneration strategies aimed at restoring and rejuvenating aging cardiovascular tissues. Altered redox homeostasis and the accumulation of oxidative damage play a pivotal role in detrimental changes to stem cell function and...
Meret Sarah Allemann

3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex

2 weeks 4 days ago
During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in...
Zer Vue

Latent transforming growth factor beta binding protein 4: A regulator of mitochondrial function in acute kidney injury

2 weeks 4 days ago
Recently, latent transforming growth factor beta binding protein 4 (LTBP4) was implicated in the pathogenesis of renal damage through its modulation of mitochondrial dynamics. The seminal article written by Su et al. entitled "LTBP4 (Latent Transforming Growth Factor Beta Binding Protein 4) Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts" uncovers LTBP4's renoprotective role against acute kidney injury via modulating mitochondrial dynamics. Recently, LTBP4 has emerged as a...
Kit Neikirk

LEF1 isoforms regulate cellular senescence and aging

2 weeks 4 days ago
The study of aging and its mechanisms, such as cellular senescence, has provided valuable insights into age-related pathologies, thus contributing to their prevention and treatment. The current abundance of high-throughput data combined with the surge of robust analysis algorithms has facilitated novel ways of identifying underlying pathways that may drive these pathologies. For the purpose of identifying key regulators of lung aging, we performed comparative analyses of transcriptional profiles...
Minxue Jia

Calorie restriction reduces biomarkers of cellular senescence in humans

2 weeks 4 days ago
Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR...
Zaira Aversa

NAD<sup>+</sup> regulates nucleotide metabolism and genomic DNA replication

2 weeks 5 days ago
The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD^(+)) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD^(+) plays a key role in regulating metabolic pathways, such as glycolysis and Kreb's cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD^(+) to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid...
Sebastian Howen Nesgaard Munk

Refeeding-associated AMPK<sub>γ1</sub> complex activity is a hallmark of health and longevity

2 weeks 5 days ago
Late-life-initiated dietary interventions show limited efficacy in extending longevity or mitigating frailty, yet the underlying causes remain unclear. Here we studied the age-related fasting response of the short-lived killifish Nothobranchius furzeri. Transcriptomic analysis uncovered the existence of a fasting-like transcriptional program in the adipose tissue of old fish that overrides the feeding response, setting the tissue in persistent metabolic quiescence. The fasting-refeeding cycle...
Roberto Ripa

A drug-like molecule engages nuclear hormone receptor DAF-12/FXR to regulate mitophagy and extend lifespan

2 weeks 5 days ago
Autophagy-lysosomal function is crucial for maintaining healthy lifespan and preventing age-related diseases. The transcription factor TFEB plays a key role in regulating this pathway. Decreased TFEB expression is associated with various age-related disorders, making it a promising therapeutic target. In this study, we screened a natural product library and discovered mitophagy-inducing coumarin (MIC), a benzocoumarin compound that enhances TFEB expression and lysosomal function. MIC robustly...
Manish Chamoli

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

2 weeks 5 days ago
Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) is linked to severe neurological manifestations. Senescent cells contribute to brain aging, but the impact of virus-induced senescence on neuropathologies is unknown. Here we show that senescent cells accumulate in aged human brain organoids and that senolytics reduce age-related inflammation and rejuvenate transcriptomic aging clocks. In postmortem brains of patients with severe COVID-19 we...
Julio Aguado

Pharmacological modulation of vascular ageing: A review from VascAgeNet

2 weeks 5 days ago
Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides...
Lynn Roth

The function of BCL11B in base excision repair contributes to its dual role as an oncogene and a haplo-insufficient tumor suppressor gene

2 weeks 5 days ago
Genetic studies in mice and human cancers established BCL11B as a haploinsufficient tumor suppressor gene. Paradoxically, BCL11B is overexpressed in some human cancers where its knockdown is synthetic lethal. We identified the BCL11B protein in a proximity-dependent biotinylation screen performed with the DNA glycosylase NTHL1. In vitro DNA repair assays demonstrated that both BCL11B and a small recombinant BCL11B213-560 protein lacking transcription regulation potential can stimulate the...
Elise Vickridge

Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone

2 weeks 6 days ago
Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to a pro-neurogenic microglial phenotype in the V-SVZ...
Vivianne Morrison

Skeletal muscle TFEB signaling promotes central nervous system function and reduces neuroinflammation during aging and neurodegenerative disease

2 weeks 6 days ago
Skeletal muscle has recently arisen as a regulator of central nervous system (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here, we report the generation of a transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of transcription factor E-B (TFEB). We discovered that the resulting geroprotective effects in skeletal muscle reduce...
Ian Matthews

RNF14-dependent atypical ubiquitylation promotes translation-coupled resolution of RNA-protein crosslinks

3 weeks ago
Reactive aldehydes are abundant endogenous metabolites that challenge homeostasis by crosslinking cellular macromolecules. Aldehyde-induced DNA damage requires repair to prevent cancer and premature aging, but it is unknown whether cells also possess mechanisms that resolve aldehyde-induced RNA lesions. Here, we establish photoactivatable ribonucleoside-enhanced crosslinking (PAR-CL) as a model system to study RNA crosslinking damage in the absence of confounding DNA damage in human cells. We...
Shubo Zhao

Stress-induced β cell early senescence confers protection against type 1 diabetes

3 weeks 1 day ago
During the progression of type 1 diabetes (T1D), β cells are exposed to significant stress and, therefore, require adaptive responses to survive. The adaptive mechanisms that can preserve β cell function and survival in the face of autoimmunity remain unclear. Here, we show that the deletion of the unfolded protein response (UPR) genes Atf6α or Ire1α in β cells of non-obese diabetic (NOD) mice prior to insulitis generates a p21-driven early senescence phenotype and alters the β cell secretome...
Hugo Lee

Cholesterol 24-hydroxylase at the choroid plexus contributes to brain immune homeostasis

3 weeks 2 days ago
The choroid plexus (CP) plays a key role in remotely controlling brain function in health, aging, and disease. Here, we report that CP epithelial cells express the brain-specific cholesterol 24-hydroxylase (CYP46A1) and that its levels are decreased under different mouse and human brain conditions, including amyloidosis, aging, and SARS-CoV-2 infection. Using primary mouse CP cell cultures, we demonstrate that the enzymatic product of CYP46A1, 24(S)-hydroxycholesterol, downregulates inflammatory...
Afroditi Tsitsou-Kampeli

Lifestyle effects on aging and CVD: A spotlight on the nutrient-sensing network

3 weeks 2 days ago
Aging is widespread worldwide and a significant risk factor for cardiovascular disease (CVD). Mechanisms underlying aging have attracted considerable attention in recent years. Remarkably, aging and CVD overlap in numerous ways, with deregulated nutrient sensing as a common mechanism and lifestyle as a communal modifier. Interestingly, lifestyle triggers or suppresses multiple nutrient-related signaling pathways. In this review, we first present the composition of the nutrient-sensing network...
Kaiying Yang

Functional alterations of the prefrontal circuit underlying cognitive aging in mice

3 weeks 2 days ago
Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in the mouse medial prefrontal cortex (mPFC) are altered as early as middle age. Population activity in the young adult mPFC exhibits dissociable yet overlapping patterns between tactile and auditory...
Huee Ru Chong

Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance

3 weeks 2 days ago
We recently reported accelerated cognitive decline in Europeans aged > 70 years with low circulating adropin levels. Adropin is a small, secreted peptide that is highly expressed in the human nervous system. Expression profiling indicate relationships between adropin expression in the human brain and pathways that affect dementia risk. Moreover, increased adropin expression or treatment using synthetic adropin improves cognition in mouse models of aging. Here we report that low circulating...
Geetika Aggarwal
20 minutes 16 seconds ago
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