Leader: Flavia Valtorta (UNISR); Other collaborator(s):
We aim at investigating key mechanisms of age-related cellular and tissue damage in two major areas: inflammation and cellular fitness. Intra- and inter-cellular inflammatory mechanisms will include cellular senescence, HMGB1, sphingolipids, hypoxia and necroptosis. Key determinants of cellular fitness will include mechanisms conferring adaptive properties or selective susceptibility to aging, bioenergetic, organelles and proteome plasticity. Major areas of investigation will include metabolism, receptors and signal transduction, proteostasis and autophagy, translational control of organelle biogenesis and function, and protein quality control.
Brief description of the activities and of the intermediate results: We investigated key mechanisms of age-related cellular and tissue damage in two major areas, inflammation and cellular fitness. We have performed RNA seq analyses on substantia nigra of mice carrying mutations in the PRKN gene and wild-type controls at 1 and 6 months of age, which showed differential expression of genes correlated with inflammation, cell death, and ubiquitination. We characterized the molecular mechanisms regulating protein synthesis in secretory cells with immunoglobulin-producing plasma cells as a privileged model, focusing on two RNA methyltransferases (BUD23/TRMT112) regulating ribosome biogenesis and protein translation efficiency essential to maintain secretory homeostasis and cell survival. We characterized a novel intracellular circuit connecting protein aggregation and mitochondrial dysfunction, two fundamental drivers of aging, involving the prototypical aggrephagy receptor, SQSTM1/p62.
Aging in experimental stroke:
We are evaluating the effect of spontaneous physical training on modulating the inflammatory response and on outcome in an aged mouse model of stroke.
Investigating endosomal function in aged-related changes of post-transcriptional control of gene expression
We have established in vivo and in vitro models to study the link between aged-related endosomal defects and mRNA localization in neurons. By combining genome-wide analysis and imaging approaches, we are currently investigating the changes in the early-endosomal associated transcriptome in neurons during aging.
Investigating aging features in mouse models of PD
We are studying the mechanisms of neurodegeneration in a mouse model of juvenile parkinsonism, i.e. a model of accelerated aging. We found higher levels of necroptosis markers as compared to wild-type mice.
Coming soon