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Q1 2024
ISSN 2817-8831
Candidate Preprints
Q1 2024
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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

Domenico Di Fraia, Antonio Marino, Jae Ho Lee, Erika Kelmer Sacramento, Mario Baumgart, Sara Bagnoli, Pedro Tomaz da Silva, Amit Kumar Sahu, Giacomo Siano, Max Tiessen, Eva Terzibasi-Tozzini, Julien Gagneur, Judith Frydman, Alessandro Cellerino, Alessandro Ori

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.

Q1 2024
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Re-activation of neurogenic niches in aging brain

Re-activation of neurogenic niches in aging brain

Roy Maimon, Carlos Chillon-Marinas, Sonia Vazquez-Sanchez, Colin Kern, Kresna Jenie, Kseniya Malukhina, Stephen Moore, Jess Cui, Alexander Goginashvili, Siavash Moghadami, Alexander Monell, Melissa McAlonis-Downes, Christine Hong, Paymaan Jafar-Nejad, C. Frank Bennett, Quan Zhu, John Ravits, Don W. Cleveland, Bogdan Bintu

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.

Q1 2024
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A universal molecular mechanism driving aging

A universal molecular mechanism driving aging

Wan Jin, Jing Zheng, Yu Xiao, Lingao Ju, Fangjin Chen, Jie Fu, Hui Jiang, Yi Zhang

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.

Q1 2024
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A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring

A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring

Todd W. Dowrey, Samuel F. Cranston, Nicholas Skvir, Yvonne Lok, Brian Gould, Bradley Petrowitz, Daniel Villar, Jidong Shan, Marianne James, Mark Dodge, Anna C. Belkina, Richard M. Giadone, Paola Sebastiani, Thomas T. Perls, Stacy L. Andersen, George J. Murphy

This study examined longevity and healthy aging in centenarians by analyzing blood samples and reprogramming cells into induced pluripotent stem cells. Differences between biological and chronological age were assessed, creating a resource to study human resilience and develop new treatments for aging-related diseases.

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

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.

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Association between prescription drugs and all-cause mortality risk in the UK population

Association between prescription drugs and all-cause mortality risk in the UK population

By analyzing UK biobank data for over 500,000 patients and 406 medications, researchers found that most drugs negatively impacted lifespan, likely due to the underlying diseases. However, Sildenafil, Atorvastatin, Naproxen, and Estradiol showed potential lifespan benefits, warranting further investigation.

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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

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.

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Rejuvenation of Senescent Cells by Low Frequency Ultrasound without Senolysis

Rejuvenation of Senescent Cells by Low Frequency Ultrasound without Senolysis

Senescent cells treated with low frequency ultrasound (LFU) resume growth and increased motility. LFU induces Ca2+ entry, enhances autophagy, and inhibits mTORC1, reversing several senescence markers. Repeated LFU treatments extend cell replicative limits without altering phenotype. Rejuvenation is enhanced by rapamycin and Rho kinase inhibition but blocked by Sirtuin 1, Piezo1, or TRPV1 inhibition.

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