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  1. Article ; Online: The long and winding road of reprogramming-induced rejuvenation.

    Yücel, Ali Doğa / Gladyshev, Vadim N

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1941

    Abstract: Organismal aging is inherently connected to the aging of its constituent cells and systems. Reducing the biological age of the organism may be assisted by reducing the age of its cells - an approach exemplified by partial cell reprogramming through the ... ...

    Abstract Organismal aging is inherently connected to the aging of its constituent cells and systems. Reducing the biological age of the organism may be assisted by reducing the age of its cells - an approach exemplified by partial cell reprogramming through the expression of Yamanaka factors or exposure to chemical cocktails. It is crucial to protect cell type identity during partial reprogramming, as cells need to retain or rapidly regain their functions following the treatment. Another critical issue is the ability to quantify biological age as reprogrammed older cells acquire younger states. We discuss recent advances in reprogramming-induced rejuvenation and offer a critical review of this procedure and its relationship to the fundamental nature of aging. We further comparatively analyze partial reprogramming, full reprogramming and transdifferentiation approaches, assess safety concerns and emphasize the importance of distinguishing rejuvenation from dedifferentiation. Finally, we highlight translational opportunities that the reprogramming-induced rejuvenation approach offers.
    MeSH term(s) Rejuvenation ; Cellular Reprogramming/genetics
    Language English
    Publishing date 2024-03-02
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46020-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Intersection clock reveals a rejuvenation event during human embryogenesis.

    Kerepesi, Csaba / Gladyshev, Vadim N

    Aging cell

    2023  Volume 22, Issue 10, Page(s) e13922

    Abstract: Recent research revealed a rejuvenation event during early development of mice. Here, by examining epigenetic age dynamics of human embryogenesis, we tested whether a similar event exists in humans. For this purpose, we developed an epigenetic clock ... ...

    Abstract Recent research revealed a rejuvenation event during early development of mice. Here, by examining epigenetic age dynamics of human embryogenesis, we tested whether a similar event exists in humans. For this purpose, we developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples and applied it to human embryo development data. We observed no changes in the predicted epigenetic age between cleavage stage and blastocyst stage embryos; however, a significant decrease was observed between blastocysts and cells representing the epiblast. Additionally, by applying the intersection clock to datasets spanning pre and postimplantation, we found no significant change in the epigenetic age during preimplantation stages; however, the epigenetic age of postimplantation samples was lower compared to the preimplantation stages. We further investigated the epigenetic age of primed (representing early postimplantation) and naïve (representing preimplantation) pluripotent stem cells and observed that in all cases the epigenetic age of primed cells was significantly lower than that of naïve cells. Together, our data suggest that human embryos are rejuvenated during early embryogenesis. Hence, the rejuvenation event is conserved between the mouse and human, and it occurs around the gastrulation stage in both species. Beyond this advance, the intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets as opposed to methylation arrays.
    MeSH term(s) Humans ; Animals ; Mice ; Rejuvenation ; Blastocyst/metabolism ; Germ Layers ; Embryonic Development/genetics ; DNA Methylation/genetics
    Chemical Substances hydrogen sulfite (OJ9787WBLU)
    Language English
    Publishing date 2023-10-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.13922
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  3. Article ; Online: We need to shift the focus of aging research to aging itself.

    Poganik, Jesse R / Gladyshev, Vadim N

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 37, Page(s) e2307449120

    MeSH term(s) Geroscience ; Humans ; Biomedical Research
    Language English
    Publishing date 2023-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2307449120
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  4. Article ; Online: Metabolism, homeostasis, and aging.

    Moldakozhayev, Alibek / Gladyshev, Vadim N

    Trends in endocrinology and metabolism: TEM

    2023  Volume 34, Issue 3, Page(s) 158–169

    Abstract: We propose a two-mode (pursuit/maintenance) model of metabolism defined by usable resource availability. Pursuit, consisting of anabolism and catabolism, dominates when usable resources are plentiful and leads to the generation of metabolic waste. In ... ...

    Abstract We propose a two-mode (pursuit/maintenance) model of metabolism defined by usable resource availability. Pursuit, consisting of anabolism and catabolism, dominates when usable resources are plentiful and leads to the generation of metabolic waste. In turn, maintenance of a system is activated by elevated metabolic waste during resource depletion. Interaction with the environment results in pendulum-like swings between these metabolic states in thriveless attempts to maintain the least deleterious organismal state - ephemeral homeostasis. Imperfectness of biological processes during these attempts supports the accumulation of the deleteriome, driving organismal aging. We discuss how metabolic adjustment by the environment and resource stabilization may modulate healthspan and lifespan.
    MeSH term(s) Humans ; Aging/metabolism ; Longevity ; Homeostasis
    Language English
    Publishing date 2023-01-20
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1042384-9
    ISSN 1879-3061 ; 1043-2760
    ISSN (online) 1879-3061
    ISSN 1043-2760
    DOI 10.1016/j.tem.2023.01.003
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  5. Article ; Online: The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations.

    Ogrodnik, Mikolaj / Gladyshev, Vadim N

    Nature aging

    2023  Volume 3, Issue 7, Page(s) 766–775

    Abstract: With recent rapid progress in research on aging, there is increasing evidence that many features commonly considered to be mechanisms or drivers of aging in fact represent adaptations. Here, we examine several such features, including cellular senescence, ...

    Abstract With recent rapid progress in research on aging, there is increasing evidence that many features commonly considered to be mechanisms or drivers of aging in fact represent adaptations. Here, we examine several such features, including cellular senescence, epigenetic aging and stem cell alterations. We draw a distinction between the causes and consequences of aging and define short-term consequences as 'responses' and long-term ones as 'adaptations'. We also discuss 'damaging adaptations', which despite having beneficial effects in the short term, lead to exacerbation of the initial insult and acceleration of aging. Features commonly recognized as 'basic mechanisms of the aging process' are critically examined for the possibility of their adaptation-driven emergence from processes such as cell competition and the wound-like features of the aging body. Finally, we speculate on the meaning of these interactions for the aging process and their relevance for the development of antiaging interventions.
    MeSH term(s) Cellular Senescence/genetics ; Stem Cells ; Acclimatization ; Epigenesis, Genetic
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2662-8465
    ISSN (online) 2662-8465
    DOI 10.1038/s43587-023-00447-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The Ground Zero of Organismal Life and Aging.

    Gladyshev, Vadim N

    Trends in molecular medicine

    2020  Volume 27, Issue 1, Page(s) 11–19

    Abstract: Cells may naturally proceed or be forced to transition to a state with a radically lower biological age, that is, be rejuvenated. Examples are the conversion of somatic cells to induced pluripotent stem cells and rejuvenation of the germline with each ... ...

    Abstract Cells may naturally proceed or be forced to transition to a state with a radically lower biological age, that is, be rejuvenated. Examples are the conversion of somatic cells to induced pluripotent stem cells and rejuvenation of the germline with each generation. We posit that these processes converge to the same 'ground zero', the mid-embryonic state characterized by the lowest biological age where both organismal life and aging begin. It may also be related to the phylotypic state. The ground zero model clarifies the relationship between aging, development, rejuvenation, and de-differentiation, which are distinct throughout life. By extending the rejuvenation phase during early embryogenesis and editing the genome, it may be possible to achieve the biological age at the ground zero lower than that achieved naturally.
    MeSH term(s) Aging/physiology ; Animals ; Embryonic Development/physiology ; Genomics ; Humans ; Longevity ; Rejuvenation
    Language English
    Publishing date 2020-09-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2036490-8
    ISSN 1471-499X ; 1471-4914
    ISSN (online) 1471-499X
    ISSN 1471-4914
    DOI 10.1016/j.molmed.2020.08.012
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    Zs.A 4345: Show issues Location:
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  7. Article ; Online: Selenocysteine Machinery Primarily Supports TXNRD1 and GPX4 Functions and Together They Are Functionally Linked with SCD and PRDX6.

    Santesmasses, Didac / Gladyshev, Vadim N

    Biomolecules

    2022  Volume 12, Issue 8

    Abstract: The human genome has 25 genes coding for selenocysteine (Sec)-containing proteins, whose synthesis is supported by specialized Sec machinery proteins. Here, we carried out an analysis of the co-essentiality network to identify functional partners of ... ...

    Abstract The human genome has 25 genes coding for selenocysteine (Sec)-containing proteins, whose synthesis is supported by specialized Sec machinery proteins. Here, we carried out an analysis of the co-essentiality network to identify functional partners of selenoproteins and Sec machinery. One outstanding cluster included all seven known Sec machinery proteins and two critical selenoproteins, GPX4 and TXNRD1. Additionally, these nine genes were further positively associated with PRDX6 and negatively with SCD, linking the latter two genes to the essential role of selenium. We analyzed the essentiality scores of gene knockouts in this cluster across one thousand cancer cell lines and found that Sec metabolism genes are strongly selective for a subset of primary tissues, suggesting that certain cancer cell lineages are particularly dependent on selenium. A separate outstanding cluster included selenophosphate synthetase SEPHS1, which was linked to a group of transcription factors, whereas the remaining selenoproteins were linked neither to these clusters nor among themselves. The data suggest that key components of Sec machinery have already been identified and that their primary role is to support the functions of GPX4 and TXNRD1, with further functional links to PRDX6 and SCD.
    MeSH term(s) Cell Line ; Genome, Human ; Humans ; Peroxiredoxin VI/genetics ; Peroxiredoxin VI/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Selenium/metabolism ; Selenocysteine/genetics ; Selenocysteine/metabolism ; Selenoproteins/genetics ; Selenoproteins/metabolism ; Stearoyl-CoA Desaturase/metabolism ; Thioredoxin Reductase 1/genetics ; Thioredoxin Reductase 1/metabolism
    Chemical Substances Selenoproteins ; Selenocysteine (0CH9049VIS) ; Phospholipid Hydroperoxide Glutathione Peroxidase (EC 1.11.1.12) ; PRDX6 protein, human (EC 1.11.1.15) ; Peroxiredoxin VI (EC 1.11.1.15) ; SCD1 protein, human (EC 1.14.19.1) ; Stearoyl-CoA Desaturase (EC 1.14.19.1) ; TXNRD1 protein, human (EC 1.8.1.9) ; Thioredoxin Reductase 1 (EC 1.8.1.9) ; Selenium (H6241UJ22B)
    Language English
    Publishing date 2022-07-28
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12081049
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  8. Book: Selenium

    Hatfield, Dolph L. / Berry, Marla J. / Gladyshev, Vadim N.

    its molecular biology and role in human health

    2012  

    Author's details Dolph L. Hatfield ; Marla J. Berry ; Vadim N. Gladyshev
    Keywords Selenium / physiology ; Selenium / deficiency ; Selenium / therapeutic use ; Proteins / metabolism ; Antioxidants ; Selenium ; Molecular biology ; Selenium/Physiological effect ; Sehen ; Molekularbiologie ; Gesundheit
    Subject Gesundheitsstatus ; Gesundheitszustand ; Gesichtssinn ; Sehvorgang ; Molekulare Biologie
    Subject code 572.555
    Language English
    Size XXV, 598 S. : Ill., graph. Darst., 25cm
    Edition 3. ed
    Publisher Springer
    Publishing place New York u.a.
    Publishing country United States
    Document type Book
    Note Includes bibliographical references and index
    HBZ-ID HT017071009
    ISBN 978-1-4614-1024-9 ; 9781461410256 ; 1-4614-1024-X ; 1461410258
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2011 A 5485 order for loan Magazin

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  9. Article ; Online: Accelerated transcriptional elongation during aging impairs longevity.

    Tyshkovskiy, Alexander / Zhang, Sirui / Gladyshev, Vadim N

    Cell research

    2023  Volume 33, Issue 11, Page(s) 817–818

    MeSH term(s) Longevity/genetics ; Oxidative Stress
    Language English
    Publishing date 2023-05-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1319303-x
    ISSN 1748-7838 ; 1001-0602
    ISSN (online) 1748-7838
    ISSN 1001-0602
    DOI 10.1038/s41422-023-00829-9
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    Full text online

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    Zs.A 5283: Show issues Location:
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  10. Article ; Online: Pathogenic Variants in Selenoproteins and Selenocysteine Biosynthesis Machinery.

    Santesmasses, Didac / Gladyshev, Vadim N

    International journal of molecular sciences

    2021  Volume 22, Issue 21

    Abstract: Selenium is incorporated into selenoproteins as the 21st amino acid selenocysteine (Sec). There are 25 selenoproteins encoded in the human genome, and their synthesis requires a dedicated machinery. Most selenoproteins are oxidoreductases with important ... ...

    Abstract Selenium is incorporated into selenoproteins as the 21st amino acid selenocysteine (Sec). There are 25 selenoproteins encoded in the human genome, and their synthesis requires a dedicated machinery. Most selenoproteins are oxidoreductases with important functions in human health. A number of disorders have been associated with deficiency of selenoproteins, caused by mutations in selenoprotein genes or Sec machinery genes. We discuss mutations that are known to cause disease in humans and report their allele frequencies in the general population. The occurrence of protein-truncating variants in the same genes is also presented. We provide an overview of pathogenic variants in selenoproteins genes from a population genomics perspective.
    MeSH term(s) Alleles ; Animals ; Genetic Variation/genetics ; Genome, Human/genetics ; Humans ; Selenium/metabolism ; Selenocysteine/genetics ; Selenoproteins/genetics
    Chemical Substances Selenoproteins ; Selenocysteine (0CH9049VIS) ; Selenium (H6241UJ22B)
    Language English
    Publishing date 2021-10-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222111593
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