Biology subjects

Kasturi, P.

Publications and source records attributed to Kasturi, P..

4 recordsLinked to original sources

bioRxiv2026

Identification of conserved age-associated aggregation-prone proteins for natural molecule targeting during aging in Caenorhabditis elegans

Aging is associated with proteome remodelling and progressive accumulation of insoluble proteins. Identifying age-enriched proteins that undergo aggregation and evaluating compounds capable of modulating their behaviour may provide insights into interventions that promote healthy aging. Here, we report a proteome-guided strategy to identify age-associated aggregation-prone proteins and evaluate phytochemicals targeting conserved proteins in Caenorhabditis elegans. We identified proteins whose abundance increased more than four-fold in aged worms compared with young worms, many of which also accumulated in the age-associated insoluble proteome, and subsequently identified their human orthologs for comparative analysis. Based on biological relevance, structural conservation, and availability of high-confidence structural models, glutamine-fructose-6-phosphate aminotransferase-2 (GFAT-2) was selected for molecular docking. Screening of fifteen phytochemicals against C. elegans GFAT-2 and its human ortholog GFPT1 identified quercetin as the strongest predicted binder, exhibiting conserved interactions with both proteins. However, treatment of worms with quercetin did not significantly alter global protein insolubility during aging. This may reflect its ability to modulate inappropriate protein-protein interactions without substantially affecting the overall aggregation burden. These findings underscore the need for experimental validation of favourable in silico docking predictions. More broadly, this study provides a proteome-guided framework for prioritizing age-associated aggregation-prone proteins as candidate therapeutic targets for preserving proteostasis during aging.

biochemistry↗

bioRxiv2024

A meta-analysis of age-dependent changes in extracellular vesicle proteins in C. elegans

Extracellular vesicles (EVs) contribute to the maintenance of organism-wide proteostasis by mediating intercellular communication. Loss of proteostasis and altered intercellular communication are associated with aging and age-related diseases, suggesting key roles for EVs. However, it is unclear how the proteome of the EVs changes with age. To identify EV-associated proteins (EVAPs) and their fate with age, we curated publicly available proteome data from C. elegans model organism. Our analysis reveals that EVs carry proteins that involve protein quality control. We found that abundance of the EV proteins changes significantly with age. Many of these EV proteins also aggregate with age and overlap with A{beta} driven protein aggregates. We also observe that a subset of proteins that alter their abundance in response to heat stress and pathogen infections are also associated with the EVs. Further, we identify human orthologs of C. elegans EVAPs from human brain tissues affected with Alzheimers disease. This meta-analysis highlights EVs proteome composition, their abundance changes, and aggregation during aging, disease and stress conditions. Overall, this study provides new insights into the dynamics of EV proteins during aging and may possibly help in identifying potential biomarkers for age-related diseases.

biochemistry↗

bioRxiv2024

The abundance change of age-regulated secreted proteins affects lifespan of C. elegans

Proteome integrity is vital for survival and failure to maintain it results in uncontrolled protein abundances, misfolding and aggregation which cause proteotoxicity. In multicellular organisms, proteotoxic stress is communicated among tissues to maintain proteome integrity for organismal stress resistance and survival. However, nature of these signalling molecules and their regulation in extracellular space is largely unknown. Secreted proteins are induced in response to various stresses and aging, indicating their roles in the inter tissue communication. To study fates of age-regulated proteins with potential localization to extracellular, we analysed publicly available age-related proteome data of C. elegans. We found that abundance of proteins with signal peptides (SP) increases with age and result in their aggregation. Intriguingly, these changes are differentially regulated in the lifespan mutants. A subset of these SP proteins is also found in the cargo of extracellular vesicles. Many of these proteins are novel and functionally uncharacterized. Reducing levels of a few extracellular proteins result in increasing lifespan. This suggest that uncontrolled levels of extracellular proteins might disturb proteostasis and limit the lifespan. Overall, our findings suggest that the age induced secreted proteins might be the potential candidates to be considered as biomarkers or for mitigating age-related pathological conditions.

biochemistry↗

bioRxiv2021

A comparative meta-analysis of membraneless organelle associated proteins with age related proteome of C. elegans

Proteome imbalance can lead to protein misfolding and aggregation which is associated with pathologies. Protein aggregation can also be an active, organized process and can be exploited by cells as a survival strategy. In adverse conditions, it is beneficial to deposit the proteins in a condensate rather degrading and resynthesizing. Membraneless organelles (MLOs) are biological condensates formed through liquid-liquid phase separation (LLPS), involving cellular components such as nucleic acids and proteins. LLPS is a regulated process, which when perturbed, can undergo a transition from a physiological liquid condensate to pathological solid-like protein aggregates. To understand how the MLO-associated proteins (MLO-APs) behave during aging, we performed a comparative meta-analysis with age related proteome of C. elegans. We found that the MLO-APs are highly abundant throughout the lifespan. Interestingly, they are aggregating more in long-lived mutant worms compared to the age matched wildtype worms. GO term analysis revealed that the cell cycle and embryonic development are among the top enriched processes in addition to RNP components in insoluble proteome. Considering antagonistic pleotropic nature of these developmental genes and post mitotic status of C. elegans, we assume that these proteins phase transit during post development. As the organism ages, these MLO-APs either mature to become more insoluble or dissolve in uncontrolled manner. However, in the long-lived daf-2 mutant worms, the MLOs may attain protective states due to extended availability and association of molecular chaperones.

biochemistry↗