Lysosomal alkalinization in nutrient restricted cancer cells activates cytoskeletal rearrangement to enhance partial epithelial to mesenchymal transition DOI Creative Commons
Hepşen Hazal Hüsnügil, Aliye Ezgi Güleç Taşkıran, İsmail Güderer

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 41, P. 101860 - 101860

Published: Jan. 22, 2024

Nutrient restriction in cancer cells can activate a number of stress response pathways for cell survival. We aimed to determine mechanistically how nutrient depletion colorectal (CRC) leads cellular adaptation. Cell survival under (ND) was evaluated by colony formation and vivo tumor assays. Lysosomes are activated with ND; therefore, we incubated the ND V-ATPase inhibitor Bafilomycin A1 (ND+Baf). The expression epithelial mesenchymal markers ND+Baf determined RNA sequencing RT-qPCR while motility an Chorioallantoic membrane (CAM) assay. Reorganization cytoskeletal network lysosomal positioning immunocytochemistry. 4 different lines showed high viability, forming ability increased one or more markers, suggesting activation partial (p)-EMT. observed further increase p-EMT numerous protrusions, decreased cell-cell adhesion 3D, cells. protrusions were primarily mediated microtubules enabled relocalization lysosomes from perinuclear region periphery. CRC cells, which exacerbated alkalinization. also containing lysosomes, may lead exocytosis enhanced motility.

Language: Английский

Lysosomes in senescence and aging DOI
Xiaojun Tan, Toren Finkel

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(11)

Published: Oct. 9, 2023

Language: Английский

Citations

46
Human Skin Aging and the Anti-Aging Properties of Retinol DOI Creative Commons
Taihao Quan

Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1614 - 1614

Published: Nov. 4, 2023

The skin is the most-extensive and -abundant tissue in human body. Like many organs, as we age, experiences gradual atrophy both epidermis dermis. This can be primarily attributed to diminishing population of epidermal stem cells reduction collagen, which primary structural protein alterations occurring dermis due aging process result disruptions structure functionality skin. creates a microenvironment conducive age-related conditions such compromised barrier, slowed wound healing, onset cancer. review emphasizes recent molecular discoveries related evaluates preventive approaches, use topical retinoids. Topical retinoids have demonstrated promise enhancing texture, fine lines, augmenting thickness dermal layers.

Language: Английский

Citations

42
Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases DOI

Qing Zeng,

Yongzhen Gong,

Neng Zhu

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102294 - 102294

Published: April 5, 2024

Language: Английский

Citations

33
A TBK1-independent primordial function of STING in lysosomal biogenesis DOI
Bo Lv, William Dion, Haoxiang Yang

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(20), P. 3979 - 3996.e9

Published: Sept. 19, 2024

Language: Английский

Citations

10
Regulation of cGAS–STING signalling and its diversity of cellular outcomes DOI
Zhengyin Zhang, Conggang Zhang

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

Citations

1
mTOR activation induces endolysosomal remodeling and nonclassical secretion of IL-32 via exosomes in inflammatory reactive astrocytes DOI Creative Commons
Kun Leng, Brendan Rooney, Frank McCarthy

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 8, 2024

Astrocytes respond and contribute to neuroinflammation by adopting inflammatory reactive states. Although recent efforts have characterized the gene expression signatures associated with these states, cell biology underlying astrocyte phenotypes remains under-explored. Here, we used CRISPR-based screening in human iPSC-derived astrocytes identify mTOR activation a driver of cytokine-induced endolysosomal system remodeling, manifesting as alkalinization compartments, decreased autophagic flux, increased exocytosis certain cargos. Through proteomics, identified focused on one such cargo-IL-32, disease-associated pro-inflammatory cytokine not present rodents, whose secretion mechanism is well understood. We found that IL-32 was partially secreted extracellular vesicles likely be exosomes. Furthermore, involved polarization states upregulated multiple sclerosis lesions. believe our results advance understanding biological pathways potential therapeutic targets.

Language: Английский

Citations

6
Lysosome Functions in Atherosclerosis: A Potential Therapeutic Target DOI Creative Commons
Zhengchao Wang,

Xiang Li,

Alexandra K. Moura

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 183 - 183

Published: Jan. 24, 2025

Lysosomes in mammalian cells are recognized as key digestive organelles, containing a variety of hydrolytic enzymes that enable the processing both endogenous and exogenous substrates. These organelles digest various macromolecules recycle them through autophagy–lysosomal system. Recent research has expanded our understanding lysosomes, identifying not only centers degradation but also crucial regulators nutrient sensing, immunity, secretion, other vital cellular functions. The lysosomal pathway plays significant role vascular regulation is implicated diseases such atherosclerosis. During atherosclerotic plaque formation, macrophages initially engulf large quantities lipoproteins, triggering pathogenic responses include dysfunction, foam cell subsequent atherosclerosis development. Lysosomal along with inefficient apoptotic accumulation modified low-density negatively impacts lesion progression. studies have highlighted dysfunction contributes critically to cell- stage-specific manner. In this review, we discuss mechanisms biogenesis its regulatory lesions. Based on these functions, propose targeting lysosomes could offer novel therapeutic approach for atherosclerosis, shedding light connection between disease progression while offering new insights into potential anti-atherosclerotic strategies.

Language: Английский

Citations

0
Raman Spectroscopy in Cellular and Tissue Aging Research DOI Creative Commons
Jeong Hee Kim, Daejong Yang, Seungman Park

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ABSTRACT The establishment of various molecular, physiological, and genetic markers for cellular senescence aging‐associated conditions has progressed the aging study. To identify such markers, a combination optical, proteomic‐, sequencing‐based tools is primarily used, often accompanying extrinsic labels. Yet, clinical detection at cellular, tissue levels are still lacking which profoundly hinders advancements in specific timely prevention aging‐related diseases pathologies. Raman spectroscopy, with its capability rapid, label‐free, non‐invasive analysis molecular compositions alterations cells tissues, holds considerable promise vivo applications. In this review, we present recent application spectroscopy to study tissues. We explore use related techniques detecting senescence, focusing on that accompany these processes. Subsequently, provide review identifying changes molecules within tissues organs.

Language: Английский

Citations

0
Exploring melatonin's signalling pathways in the protection against age-related skin deterioration DOI
Maryam Taheri, Farnoosh Seirafianpour,

Amirali Fallahian

et al.

Pharmacological Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Language: Английский

Citations

0
Aging, cellular senescence and Parkinson's disease DOI Creative Commons
Yue Ma, Madalynn Erb, Darren J. Moore

et al.

Journal of Parkinson s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting 1–2% of people over age 65. The risk developing PD dramatically increases with advanced age, indicating that aging likely a driving factor in neuropathogenesis. Several age-associated biological changes are also hallmarks neuropathology, including mitochondrial dysfunction, oxidative stress, and neuroinflammation. Accumulation senescent cells an important feature contributes to age-related diseases. How cellular senescence affects brain health whether this phenomenon neuropathogenesis not yet fully understood. In review, we highlight aging, loss proteostasis, genomic instability telomere attrition relation well established neuropathological pathways. We then discuss context neuroscience review studies directly examine PD. Studying presents challenges holds promise for advancing our understanding mechanisms, which could contribute development effective disease-modifying therapeutics. Targeting or modulating senescence-associated secretory phenotype (SASP) requires comprehensive complex relationship between pathogenesis senescence.

Language: Английский

Citations

0