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  1. AU="Wilson, Kenneth A."
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  1. Article ; Online: The understudied links of the retromer complex to age-related pathways.

    Wilson, Kenneth A

    GeroScience

    2021  Volume 44, Issue 1, Page(s) 19–24

    Abstract: Neuronal aging is associated with numerous diseases resulting in memory impairment and functional decline. A common hallmark of these disorders is the accumulation of intracellular and extracellular protein aggregates. The retromer complex plays a ... ...

    Abstract Neuronal aging is associated with numerous diseases resulting in memory impairment and functional decline. A common hallmark of these disorders is the accumulation of intracellular and extracellular protein aggregates. The retromer complex plays a central role in sorting proteins by marking them for reuse rather than degradation. Retromer dysfunction has been shown to induce protein aggregates and neurodegeneration, suggesting that it may be important for age-related neuronal decline and disease progression. Despite this, little is known about how aging influences retromer stability and the proteins with which it interacts. Detailed insights into age-dependent changes in retromer structure and function could provide valuable information towards treating and preventing many age-related neurodegenerative disorders. Here, we visit age-related pathways which interact with retromer function that ought to be further explored to determine its role in age-related neurodegeneration.
    MeSH term(s) Humans ; Neurodegenerative Diseases ; Neurons/metabolism ; Protein Transport/physiology
    Language English
    Publishing date 2021-08-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-021-00430-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1502: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Ketones to the rescue of the starving fly.

    Wilson, Kenneth A / Bar, Sudipta / Kapahi, Pankaj

    Nature metabolism

    2022  Volume 4, Issue 2, Page(s) 159–160

    Language English
    Publishing date 2022-02-17
    Publishing country Germany
    Document type Journal Article
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-022-00527-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Haste makes waste: The significance of translation fidelity for development and longevity

    Wilson, Kenneth A. / Bar, Sudipta / Kapahi, Pankaj

    Molecular cell. 2021 Sept. 16, v. 81, no. 18

    2021  

    Abstract: We highlight Martinez-Miguel et al. (2021), which demonstrates that an amino acid substitution in RPS23 found in thermophilic archaea contributes to increased translation fidelity, lifespan, and stress response but slows development and reproduction in ... ...

    Abstract We highlight Martinez-Miguel et al. (2021), which demonstrates that an amino acid substitution in RPS23 found in thermophilic archaea contributes to increased translation fidelity, lifespan, and stress response but slows development and reproduction in other organisms.
    Keywords amino acid substitution ; longevity ; reproduction ; stress response ; thermophilic archaea ; wastes
    Language English
    Dates of publication 2021-0916
    Size p. 3675-3676.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.08.036
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  4. Article ; Online: Haste makes waste: The significance of translation fidelity for development and longevity.

    Wilson, Kenneth A / Bar, Sudipta / Kapahi, Pankaj

    Molecular cell

    2021  Volume 81, Issue 18, Page(s) 3675–3676

    Abstract: We highlight Martinez-Miguel et al. (2021), which demonstrates that an amino acid substitution in RPS23 found in thermophilic archaea contributes to increased translation fidelity, lifespan, and stress response but slows development and reproduction in ... ...

    Abstract We highlight Martinez-Miguel et al. (2021), which demonstrates that an amino acid substitution in RPS23 found in thermophilic archaea contributes to increased translation fidelity, lifespan, and stress response but slows development and reproduction in other organisms.
    MeSH term(s) Longevity/genetics ; Reproduction
    Language English
    Publishing date 2021-09-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.08.036
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5055: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  5. Article: Humanin-induced autophagy plays important roles in skeletal muscle function and lifespan extension

    Kim, Su-Jeong / Devgan, Anjali / Miller, Brendan / Lee, Sam Mool / Kumagai, Hiroshi / Wilson, Kenneth A. / Wassef, Gabriella / Wong, Richard / Mehta, Hemal H. / Cohen, Pinchas / Yen, Kelvin

    Biochimica et biophysica acta. 2022 Jan., v. 1866, no. 1

    2022  

    Abstract: Autophagy, a highly conserved homeostatic mechanism, is essential for cell survival. The decline of autophagy function has been implicated in various diseases as well as aging. Although mitochondria play a key role in the autophagy process, whether ... ...

    Abstract Autophagy, a highly conserved homeostatic mechanism, is essential for cell survival. The decline of autophagy function has been implicated in various diseases as well as aging. Although mitochondria play a key role in the autophagy process, whether mitochondrial-derived peptides are involved in this process has not been explored.We developed a high through put screening method to identify potential autophagy inducers among mitochondrial-derived peptides. We used three different cell lines, mice, c.elegans, and a human cohort to validate the observation.Humanin, a mitochondrial-derived peptide, increases autophagy and maintains autophagy flux in several cell types. Humanin administration increases the expression of autophagy-related genes and lowers accumulation of harmful misfolded proteins in mice skeletal muscle, suggesting that humanin-induced autophagy potentially contributes to the improved skeletal function. Moreover, autophagy is a critical role in humanin-induced lifespan extension in C. elegans.Humanin is an autophagy inducer.This paper presents a significant, novel discovery regarding the role of the mitochondrial derived peptide humanin in autophagy regulation and as a possible therapeutic target for autophagy in various age-related diseases.
    Keywords autophagy ; cell viability ; humans ; longevity ; mitochondria ; peptides ; skeletal muscle ; therapeutics
    Language English
    Dates of publication 2022-01
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 840755-1
    ISSN 0304-4165
    ISSN 0304-4165
    DOI 10.1016/j.bbagen.2021.130017
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    Uc I Zs.247: Show issues Location:
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  6. Article ; Online: Longitudinal fundus imaging and its genome-wide association analysis provide evidence for a human retinal aging clock.

    Ahadi, Sara / Wilson, Kenneth A / Babenko, Boris / McLean, Cory Y / Bryant, Drew / Pritchard, Orion / Kumar, Ajay / Carrera, Enrique M / Lamy, Ricardo / Stewart, Jay M / Varadarajan, Avinash / Berndl, Marc / Kapahi, Pankaj / Bashir, Ali

    eLife

    2023  Volume 12

    Abstract: Biological age, distinct from an individual's chronological age, has been studied extensively through predictive aging clocks. However, these clocks have limited accuracy in short time-scales. Here we trained deep learning models on fundus images from ... ...

    Abstract Biological age, distinct from an individual's chronological age, has been studied extensively through predictive aging clocks. However, these clocks have limited accuracy in short time-scales. Here we trained deep learning models on fundus images from the EyePACS dataset to predict individuals' chronological age. Our retinal aging clocking, 'eyeAge', predicted chronological age more accurately than other aging clocks (mean absolute error of 2.86 and 3.30 years on quality-filtered data from EyePACS and UK Biobank, respectively). Additionally, eyeAge was independent of blood marker-based measures of biological age, maintaining an all-cause mortality hazard ratio of 1.026 even when adjusted for phenotypic age. The individual-specific nature of eyeAge was reinforced via multiple GWAS hits in the UK Biobank cohort. The top GWAS locus was further validated via knockdown of the fly homolog,
    MeSH term(s) Humans ; Child, Preschool ; Genome-Wide Association Study ; Aging/genetics ; Retina ; Fundus Oculi ; Diagnostic Imaging ; Epigenesis, Genetic
    Language English
    Publishing date 2023-04-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.82364
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  7. Article: Systems biology and machine learning approaches identify metabolites that influence dietary lifespan and healthspan responses across flies and humans.

    Hilsabeck, Tyler A U / Narayan, Vikram P / Wilson, Kenneth A / Carrera, Enrique / Raftery, Daniel / Promislow, Daniel / Brem, Rachel B / Campisi, Judith / Kapahi, Pankaj

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To ... ...

    Abstract Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from
    Language English
    Publishing date 2023-12-04
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.09.548232
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  8. Article ; Online: Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience.

    Wilson, Kenneth A / Chamoli, Manish / Hilsabeck, Tyler A / Pandey, Manish / Bansal, Sakshi / Chawla, Geetanjali / Kapahi, Pankaj

    Cell metabolism

    2021  Volume 33, Issue 11, Page(s) 2142–2173

    Abstract: Dietary restriction (DR) has long been viewed as the most robust nongenetic means to extend lifespan and healthspan. Many aging-associated mechanisms are nutrient responsive, but despite the ubiquitous functions of these pathways, the benefits of DR ... ...

    Abstract Dietary restriction (DR) has long been viewed as the most robust nongenetic means to extend lifespan and healthspan. Many aging-associated mechanisms are nutrient responsive, but despite the ubiquitous functions of these pathways, the benefits of DR often vary among individuals and even among tissues within an individual, challenging the aging research field. Furthermore, it is often assumed that lifespan interventions like DR will also extend healthspan, which is thus often ignored in aging studies. In this review, we provide an overview of DR as an intervention and discuss the mechanisms by which it affects lifespan and various healthspan measures. We also review studies that demonstrate exceptions to the standing paradigm of DR being beneficial, thus raising new questions that future studies must address. We detail critical factors for the proposed field of precision nutrigeroscience, which would utilize individualized treatments and predict outcomes using biomarkers based on genotype, sex, tissue, and age.
    MeSH term(s) Aging ; Caloric Restriction ; Humans ; Longevity/genetics
    Language English
    Publishing date 2021-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2021.08.018
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    Zs.A 6169: Show issues Location:
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  9. Article ; Online: OXR1 maintains the retromer to delay brain aging under dietary restriction.

    Wilson, Kenneth A / Bar, Sudipta / Dammer, Eric B / Carrera, Enrique M / Hodge, Brian A / Hilsabeck, Tyler A U / Bons, Joanna / Brownridge, George W / Beck, Jennifer N / Rose, Jacob / Granath-Panelo, Melia / Nelson, Christopher S / Qi, Grace / Gerencser, Akos A / Lan, Jianfeng / Afenjar, Alexandra / Chawla, Geetanjali / Brem, Rachel B / Campeau, Philippe M /
    Bellen, Hugo J / Schilling, Birgit / Seyfried, Nicholas T / Ellerby, Lisa M / Kapahi, Pankaj

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 467

    Abstract: Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan ... ...

    Abstract Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity.
    MeSH term(s) Humans ; Female ; Aging/genetics ; Longevity/genetics ; Neurons/metabolism ; Nervous System Diseases/metabolism ; Brain/metabolism ; Caloric Restriction ; Mitochondrial Proteins/metabolism
    Chemical Substances OXR1 protein, human ; Mitochondrial Proteins
    Language English
    Publishing date 2024-01-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44343-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Single-cell transcriptomics reveals colonic immune perturbations during amyloid-β driven Alzheimer's disease in mice.

    Makhijani, Priya / Emani, Rohini / Aguirre, Carlos Galicia / Mu, Wei-Chieh / Rane, Anand / Ng, Jenny Hong Yu / Valentino, Taylor R / Manwaring-Mueller, Max / Tan, Christopher Ryan / Du, Huixun / Wu, Fei / Khan, Saad / Wilson, Kenneth A / Winer, Shawn / Wang, Chao / Mortha, Arthur / Furman, David / Ellerby, Lisa M / Rojas, Olga L /
    Andersen, Julie K / Winer, Daniel A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-β ( ...

    Abstract The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-β (Aβ) mouse model, we uncovered AD-associated changes in ribosomal activity, oxidative stress, and BCR/plasma cell activity. Strikingly, levels of colon CXCR4
    Study highlights: AD is associated with altered immune parameters in the gut of
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.27.573841
    Database MEDical Literature Analysis and Retrieval System OnLINE

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