Aging & Longevity

Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging

2 months 2 weeks ago
Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice. Transcriptomic analysis shows marked upregulation of the type I interferon response in the retina of old mice, which correlates...
Juan Ignacio Jiménez-Loygorri

The mechanism of low blue light-induced leaf senescence mediated by GmCRY1s in soybean

2 months 2 weeks ago
Leaf senescence is a crucial trait that has a significant impact on crop quality and yield. Previous studies have demonstrated that light is a key factor in modulating the senescence process. However, the precise mechanism by which plants sense light and control senescence remains largely unknown, particularly in crop species. In this study, we reveal that the reduction in blue light under shading conditions can efficiently induce leaf senescence in soybean. The blue light receptors GmCRY1s...
Zhuang Li

Long term methionine restriction: Influence on gut microbiome and metabolic characteristics

2 months 2 weeks ago
The Methionine restriction (MR) diet has been shown to delay aging and extend lifespan in various model organisms. However, the long-term effects of MR diet on the gut microbiome composition remain unclear. To study this, male mice were started on MR and control diet regimens at 6 months and continued until 22 months of age. MR mice have reduced body weight, fat mass percentage, and bone mineral density while having increased lean mass percentage. MR mice also have increased insulin sensitivity...
Akash Nagarajan

PARP1 at the crossroad of cellular senescence and nucleolar processes

2 months 2 weeks ago
Senescent cells that occur in response to telomere shortening, oncogenes, extracellular and intracellular stress factors are characterized by permanent cell cycle arrest, the morphological and structural changes of the cell that include the senescence-associated secretory phenotype (SASP) and nucleoli rearrangement. The associated DNA lesions induce DNA damage response (DDR), which activates the DNA repair protein - poly-ADP-ribose polymerase 1 (PARP1). This protein consumes NAD^(+) to...
Kinga Kołacz

A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis

2 months 2 weeks ago
Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for β-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, β-galactosidase cleaves the O-glycosidic bond,...
Sara Rojas-Vázquez

The regulations of telomerase reverse transcriptase (TERT) in cancer

2 months 2 weeks ago
Abnormal activation of telomerase occurs in most cancer types, which facilitates escaping from cell senescence. As the key component of telomerase, telomerase reverse transcriptase (TERT) is regulated by various regulation pathways. TERT gene changing in its promoter and phosphorylation respectively leads to TERT ectopic expression at the transcription and protein levels. The co-interacting factors play an important role in the regulation of TERT in different cancer types. In this review, we...
Mingdi Liu

Epigenetic reprogramming as a key to reverse ageing and increase longevity

2 months 2 weeks ago
The pursuit for the fountain of youth has long been a fascination amongst scientists and humanity. Ageing is broadly characterized by a cellular decline with increased susceptibility to age-related diseases, being intimately associated with epigenetic modifications. Recently, reprogramming-induced rejuvenation strategies have begun to greatly alter longevity research not only to tackle age-related defects but also to possibly reverse the cellular ageing process. Hence, in this review, we...
Beatriz Pereira

Dietary Restriction Improves Perioperative Neurocognitive Disorders by Inhibiting Neuroinflammation and Gut Microbial Dysbiosis

2 months 2 weeks ago
Anesthesia/surgery have been identified as potential factors contributing to perioperative neurocognitive disorders, with a notably heightened risk observed in aging populations. One of the primary drivers of this impairment is believed to be neuroinflammation, specifically inflammation of hippocampal microglia. Dietary restriction has demonstrated a favorable impact on cognitive impairment across various disorders, primarily by quelling neuroinflammation. However, the precise influence of...
Lulu Ren

The transcription factor ZEB2 drives the formation of age-associated B cells

2 months 2 weeks ago
Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with toll-like receptor 7 (TLR7)-driven lupus, ZEB2 is essential for ABC formation...
Dai Dai

Daily activity profiles over the lifespan of female medflies as biomarkers of aging and longevity

2 months 2 weeks ago
The relationship between the early-age activity of Mediterranean fruit flies (medflies) or other fruit flies and their lifespan has not been much studied, in contrast to the connections between lifespan and diet, sexual signaling, and reproduction. The objective of this study is to assess intra-day and day-to-day activity profiles of female Mediterranean fruit flies and their role as biomarker of longevity as well as to explore the relationships between these activity profiles, diet, and...
Han Chen

In vivo imaging of synaptic density in neurodegenerative disorders with positron emission tomography: A systematic review

2 months 3 weeks ago
Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2 A (SV2A) enables quantification of synaptic density in the living human brain. Assessing the regional distribution and severity of synaptic density loss will contribute to our understanding of the pathological processes that precede atrophy in neurodegeneration. In this systematic review, we provide a discussion of in vivo SV2A PET imaging research for quantitative assessment of synaptic density in...
Malouke Visser

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

2 months 3 weeks ago
Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system...
Selim Chaib

TXNRD1 drives the innate immune response in senescent cells with implications for age-associated inflammation

2 months 3 weeks ago
Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating...
Xue Hao

Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction

2 months 3 weeks ago
Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells ('senolytics') partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the...
Corina Amor

Excessive processing and acetylation of OPA1 aggravate age-related hearing loss via the dysregulation of mitochondrial dynamics

2 months 3 weeks ago
The pathogenesis of age-related hearing loss (ARHL) remains unclear. OPA1 is the sole fusion protein currently known to be situated in the inner mitochondrial membrane, which is pivotal for maintaining normal mitochondrial function. While it has already been demonstrated that mutations in OPA1 may lead to hereditary deafness, its involvement in the occurrence and development of ARHL has not been previously explored. In our study, we constructed D-gal-induced senescent HEI-OC1 cells and the...
Andi Zhang

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin

2 months 3 weeks ago
Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here, we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. Increased TSP-1 abundance persists even after...
Wei I Jiang

DNA methylation and chromatin accessibility predict age in the domestic dog

2 months 3 weeks ago
Across mammals, the epigenome is highly predictive of chronological age. These "epigenetic clocks," most of which have been built using DNA methylation (DNAm) profiles, have gained traction as biomarkers of aging and organismal health. While the ability of DNAm to predict chronological age has been repeatedly demonstrated, the ability of other epigenetic features to predict age remains unclear. Here, we use two types of epigenetic information-DNAm, and chromatin accessibility as measured by...
Kelly Jin

Type 2 cytokine signaling in macrophages protects from cellular senescence and organismal aging

2 months 3 weeks ago
Accumulation of senescent cells in organs and tissues is a hallmark of aging and known to contribute to age-related diseases. Although aging-associated immune dysfunction, or immunosenescence, is known to contribute to this process, the underlying mechanism remains elusive. Here, we report that type 2 cytokine signaling deficiency accelerated aging and, conversely, that the interleukin-4 (IL-4)-STAT6 pathway protected macrophages from senescence. Mechanistically, activated STAT6 promoted the...
Zhao Zhou
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