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Synaptic deregulation of cholinergic projection neurons causes olfactory dysfunction across five fly Parkinsonism models

4 months ago
The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and...
Ulrike Pech

Decoding brain aging trajectory: predictive discrepancies, genetic susceptibilities, and emerging therapeutic strategies

4 months ago
The global extension of human lifespan has intensified the focus on aging, yet its underlying mechanisms remain inadequately understood. The article highlights aspects of genetic susceptibility to impaired brain bioenergetics, trends in age-related gene expression related to neuroinflammation and brain senescence, and the impact of stem cell exhaustion and quiescence on accelerated brain aging. We also review the accumulation of senescent cells, mitochondrial dysfunction, and metabolic...
Yulia Komleva

Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy

4 months ago
Immunotherapy has transformed the landscape of cancer treatment, with T cell-based strategies at the forefront of this revolution. However, the durability of these responses is frequently undermined by two intertwined phenomena: T cell exhaustion and senescence. While exhaustion is driven by chronic antigen exposure in the immunosuppressive tumor microenvironment, leading to a reversible state of diminished functionality, senescence reflects a more permanent, age- or stress-induced arrest in...
Tesfahun Dessale Admasu

Neuroprotective role of Hippo signaling by microtubule stability control in <em>Caenorhabditis elegans</em>

4 months ago
The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature...
Hanee Lee

NIA Caenorhabditis Intervention Testing Program: identification of robust and reproducible pharmacological interventions that promote longevity across experimentally accessible, genetically diverse populations

4 months ago
A core facet of the National Institute on Aging's mission is to identify pharmacological interventions that can promote human healthy aging and long life. As part of the comprehensive effort toward that goal, the NIA Division of Biology of Aging established the Caenorhabditis Intervention Testing Program (CITP) in 2013. The C. elegans model (with an ~ 21 day lifespan) has led the field in dissection of longevity genetics and offers features that allow for relatively rapid testing and for the...
Monica Driscoll

In Science Journals

4 months ago
Science, Volume 388, Issue 6742, Page 42-44, April 2025.
Michael Funk, and Sacha Vignieri, Mattia Maroso, Michael A. Funk, Marc S. Lavine, Phil Szuromi, Di Jiang, Wei Wong, Claire Olingy, Bianca Lopez, Stella M. Hurtley, Yevgeniya Nusinovich, Jake S. Yeston, Caroline Ash, Peter Stern, Madeleine Seale, Sarah H…