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Q1 2024
ISSN 2817-8831
Candidate Preprints
Q1 2024
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A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine

A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine

Bonnie L. Walton, Rebecca Shattuck-Brandt, Catherine A. Hamann, Victoria W. Tung, Juan M. Colazo, David D. Brand, Karen A. Hasty, Craig L. Duvall, Jonathan M. Brunger

A synthetic receptor platform was developed to target cell therapies for osteoarthritis (OA) to damaged cartilage. Type II collagen-specific synNotch receptors enabled engineered mesenchymal stromal cells (MSCs) to activate only in response to cartilage degeneration, expressing therapeutic genes, reducing inflammation, and promoting cartilage repair, demonstrating targeted OA treatment potential.

Q1 2024
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Differential Responses of Dynamic and Entropic Aging Factors to Longevity Interventions

Differential Responses of Dynamic and Entropic Aging Factors to Longevity Interventions

Kristina Perevoshchikova, Peter O. Fedichev

Aging in species like mice and humans shows exponential mortality rate acceleration. By analyzing DNA methylation (DNAm) in aging mice, researchers identified an aging signature with exponential age dependency, reflecting the Gompertz law. This signature aligns with aging clocks and responds to interventions like caloric restriction. Additionally, a linear DNAm signature indicates global demethylation. Single-cell DNAm data reveal this signature captures the exponential expansion of the state space volume in aging organisms, indicating linearly increasing configuration entropy, likely an irreversible process unaffected by interventions.

Q1 2024
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Rejuvenation of aged oocyte through exposure to young follicular microenvironment

Rejuvenation of aged oocyte through exposure to young follicular microenvironment

HaiYang Wang, Zhongwei Huang, Yaelim Lee, XinJie Song, Xingyu Shen, Chang Shu, Lik Hang Wu, Leroy Sivappiragasam Pakkiri, Poh Leong Lim, Xi Zhang, Chester Lee Drum, Jin Zhu, Rong Li

Reproductive aging causes fertility decline due to decreased oocyte quality. Researchers created chimeric follicles by transplanting oocytes into different follicular environments. Young oocytes in aged follicles showed reduced maturation, while aged oocytes in young follicles improved significantly. The young environment enhanced oocyte interaction with somatic cells, improved mitochondrial function, and meiotic chromosome segregation, suggesting potential follicular somatic cell-based therapies for age-related infertility.

Q1 2024
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A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine

A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine

A synthetic receptor platform was developed to target cell therapies for osteoarthritis (OA) to damaged cartilage. Type II collagen-specific synNotch receptors enabled engineered mesenchymal stromal cells (MSCs) to activate only in response to cartilage degeneration, expressing therapeutic genes, reducing inflammation, and promoting cartilage repair, demonstrating targeted OA treatment potential.

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Re-activation of neurogenic niches in aging brain

Re-activation of neurogenic niches in aging brain

Researchers used single-cell spatial transcriptomics (MERFISH) to map neurogenic niches in young and aged murine brains, finding high PTBP1 levels in glia. Suppressing PTBP1 in quiescent glia reactivated them, converting them into neurons that migrated and became GABAergic neurons. This suggests PTBP1 reduction could induce neuron generation in aged brains, offering therapeutic potential.

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Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain

Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain

In the aging brain of a short-lived killifish, researchers studied the transcriptome, translatome, and proteome. Aging causes a reduction in proteins rich in basic amino acids, independent of mRNA regulation and proteasome activity. Aberrant translation pausing reduces ribosome availability, leading to proteome remodeling. This highlights a vulnerability in the biogenesis of basic DNA/RNA binding proteins, potentially connecting various aging hallmarks.

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A universal molecular mechanism driving aging

A universal molecular mechanism driving aging

Accumulation of DNA G-quadruplexes (G4s) during cell replication drives aging mechanisms by delaying genome replication and impairing DNA re-methylation and histone modification recovery. This leads to loss of heterochromatin and progressive G4 accumulation on promoters. Mutations in G4-resolving enzymes accelerate aging, revealing a universal molecular mechanism conserved across various species.

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