Age-Related Fourier-Transform Infrared Spectroscopic Changes in Protein Conformation in an Aging Model of Human Dermal Fibroblasts DOI Open Access
Cláudia Martins, Idália Almeida, Sandra Rebelo

et al.

Spectroscopy Journal, Journal Year: 2023, Volume and Issue: 1(1), P. 37 - 48

Published: April 24, 2023

The loss of proteostasis, which results in the accumulation misfolded proteins, is one hallmarks aging and frequently associated with process. Fibroblasts are a cellular model widely used study can mimic proteostasis that occurs human body. When studying using fibroblasts, two approaches be used: fibroblasts from same donor aged vitro until senescence or donors different ages. A previous by our group showed first approach aging. Thus, this work aimed to spectroscopic profile dermal four ages Fourier-transform infrared spectroscopy identify changes protein conformation compare those obtained study. Partial least squares regression analysis peak intensity suggested older were characterized an increase levels antiparallel β-sheets decrease intermolecular β-sheets, agreement results.

Language: Английский

Chronic inflammation and the hallmarks of aging DOI Creative Commons
Jordan J. Baechle, Nan Chen, Priya Makhijani

et al.

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101755 - 101755

Published: June 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Language: Английский

Citations

156

Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration? DOI Creative Commons
Mirjam Brackhan, Marina Arribas-Blázquez, Isabel Lastres‐Becker

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(8), P. 1564 - 1564

Published: Aug. 4, 2023

Although the trigger for neurodegenerative disease process is unknown, relevance of aging stands out as a major risk development neurodegeneration. In this review, we highlighted relationship between different cellular mechanisms that occur consequence and transcription factor nuclear erythroid-2-related 2 (NRF2) connection with TAU protein. We focused on NRF2 in main processes involved neurodegeneration associated aging, such genomic instability, protein degradation systems (proteasomes/autophagy), senescence, stem cell exhaustion, well inflammation. also analyzed effect levels its aggregation spread process. Finally, investigated interconnection alterations signaling pathway both primary secondary tauopathies. All these points highlight possible therapeutic target

Language: Английский

Citations

13

Beyond youth: Understanding CAR T cell fitness in the context of immunological aging DOI Open Access
Julia Han Noll, Bruce L. Levine, Carl H. June

et al.

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 70, P. 101840 - 101840

Published: Sept. 18, 2023

Language: Английский

Citations

12

Structural Features of Pathogenic Aggregates Correlate with Cell Pathology in Differentiated Cells DOI Creative Commons
Vered Raz,

Sander Mallon,

Erik Bos

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract The accumulation of intracellular protein aggregates is a hallmark aging. In hereditary adult-onset neuromuscular diseases (NMDs), these are not only characteristic but also pathogenic, marking age-related disorders. transition from age-associated non-pathogenic to disease-driving pathogenic remains poorly understood. Poly(A) binding nuclear 1 (PABPN1) forms in post-mitotic aged cells. However, short trinucleotide expansion PABPN1 leads muscle dysfunction Oculopharyngeal Muscular Dystrophy (OPMD), where insoluble skeletal become defining disease feature. Combining an array advanced imaging modalities, we examined the morphological differences between formed by and variants. Through micro- nanoscale analyses, identified key structural aggregation propensity variants both differentiated undifferentiated cells linked mRNA cellular dysfunctions. Our findings provide new insights into distinctions their implications for diseases.

Language: Английский

Citations

0

Molecular insights into the unique properties of the blood‐circulating proteasome DOI Creative Commons

Yegor Leushkin,

David Morgenstern, Shifra Ben‐Dor

et al.

Journal of Extracellular Biology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 1, 2025

Abstract Proteasomes are essential for protein degradation and maintaining cellular balance, yet their roles in extracellular fluids not well understood. Our study investigates the freely circulating proteasome blood, to uncover its unique molecular characteristics, compared intracellular counterparts. Using a transgenic mouse model, mass spectrometry, biochemical tools, we show that predominant serum is free uncapped 20S particle, which seems assemble intracellularly before entering bloodstream. This composed of constitutive immuno subunits exhibits all three catalytic activities. Moreover, complex displays distinct post‐translational modifications, indicating specialization roles, as demonstrated by enhanced caspase‐like activity. We also found physiological stress significantly upregulates levels, paralleling human data. research highlights specialized characteristics proteasomes, offering new insights into turnover blood with significant implications understanding proteostasis beyond environment.

Language: Английский

Citations

0

Disordered peptide-based design of intrinsically disordered polymers for biomedical applications DOI
Orkid Coskuner‐Weber,

Fatma Nilsu Cayli,

Vladimir N. Uversky

et al.

International Journal of Polymer Analysis and Characterization, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 49

Published: Feb. 10, 2025

Language: Английский

Citations

0

Target Deletion or Retention of Sections After Enzyme Digestion Monitored with Attenuation-of-Sound Images DOI
Katsutoshi Miura, Toshihide Iwashita

Published: April 4, 2025

Detecting tissue components is valuable in histology. Scanning acoustic microscopy (SAM) measures the attenuation of sound (AOS) through sections to obtain histological images without need for staining. AOS values are reduced as tissues break down. Here, we digested specific using enzymes and followed process with imaging over time. Additionally, applied dyes antibodies inhibit enzyme activity preserve target component within section. Collagenase bone clearly visualise internal structure. The showed a distinct decline values. Actinase cervical artery except amyloid deposits, which were detected by Congo red Actinase-digested lymphoid cells remained horseradish peroxidase (HRP)-staining positive. Amylase some corpora amylacea (CA) brain, became periodic acid-Schiff (PAS) staining negative diminished size upon electron observation. DNase deleted cell nuclei, those stained HRP or haematoxylin. Residual nuclear matched light microscopy. Specific inhibition preserved materials. Our method offers practical solution intentionally deleting retaining Furthermore, it provides means adjust compare degree degradation

Language: Английский

Citations

0

Oxidant-Based Cytotoxic Agents During Aging: From Disturbed Energy Metabolism to Chronic Inflammation and Disease Progression DOI Creative Commons

Jürgen Arnhold

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 547 - 547

Published: April 9, 2025

In humans, aging is an inevitable consequence of diminished growth processes after reaching maturity. The high order biomolecules in cells and tissues continuously disturbed by numerous physical chemical destructive impacts. Host-derived oxidant-based cytotoxic agents (reactive species, transition free metal ions, heme) contribute considerably to this damage. These are under the control immediately acting antagonizing principles, which important ensure cell tissue homeostasis. review, I apply concept host-derived their interplay with principles process. During aging, energy metabolism supply dioxygen nutrients increasingly disturbed. addition, a chronic inflammatory state develops, condition known as inflammaging. balance between protective mechanisms analyzed depending on age-based physiological alterations ATP production. Disturbances associated development age-related diseases comorbidities. An enhanced production reactive species from dysfunctional mitochondria, cellular redox homeostasis, adaptations hypoxia highlighted. Examples how disturbances pathogenesis persons advanced age given.

Language: Английский

Citations

0

Target Deletion or Retention in Sections after Enzyme Digestion Monitored with Attenuation-of-Sound Images DOI
Katsutoshi Miura, Toshihide Iwashita

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Abstract Detecting tissue components is valuable in histology. Scanning acoustic microscopy (SAM) measures the attenuation-of-sound (AOS) through sections to obtain histological images without need for staining. AOS values are reduced as tissues break down. Here, we digested target using enzymes and followed process with imaging over time. Additionally, applied specific dyes antibodies inhibit enzyme activity preserve component. Collagenase bone clearly visualise internal structure. The component showed a distinct decline values. Actinase artery except amyloid deposits, which were detected by Congo red Actinase-digested lymphoid cells remained horseradish peroxidase (HRP)-staining positive. Amylase some corpora amylacea (CA) brain, became periodic acid-Schiff (PAS) staining negative diminished size upon electron observation. DNase deleted cell nuclei, those stained HRP. Residual nuclear of matched light microscopy. Specific inhibition preserved materials. Our method offers practical solution intentionally deleting or retaining section. Furthermore, it provides means adjust compare degree degradation 198 words

Language: Английский

Citations

0

Advancement of Targeted Protein Degradation Strategies As Therapeutics for Undruggable Disease Targets DOI

K Mayuri,

Sarojini Sreeraman,

Chaitanya Sree Somala

et al.

Future Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(10), P. 867 - 883

Published: May 1, 2023

Targeted protein degradation (TPD) aids in developing novel bifunctional small-molecule degraders and eliminates proteins of interest. The TPD approach shows promising results oncological, neurogenerative, cardiovascular gynecological drug development. We provide an overview technology advancements TPD, including molecular glues, proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimeras, antibody-based PROTAC, GlueBody autophagy-targeting chimera, autophagosome-tethering compound, chimera chaperone-mediated autophagy-based degraders. Here we discuss the development evolution field, variety that PROTACs target biological repercussions their degradation. particularly highlight recent improvements research utilize autophagy or endolysosomal pathway, which enables targeting undruggable targets.

Language: Английский

Citations

9