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  1. Article: Hallmarks of Aging: Causes and Consequences.

    Skowronska-Krawczyk, Dorota

    Aging Biology

    2024  Volume 1, Issue 1

    Abstract: In a recent review article published in Cell, López-Otín and colleagues conducted an exhaustive literature review and described 12 hallmarks of aging. The updated model of aging comprehensively captures the key characteristics of the aging phenotype and ... ...

    Abstract In a recent review article published in Cell, López-Otín and colleagues conducted an exhaustive literature review and described 12 hallmarks of aging. The updated model of aging comprehensively captures the key characteristics of the aging phenotype and incorporates new pathways that play a crucial role in age-related processes. Although the updated hallmarks of aging provide a useful framework for describing the phenotype of aging, aging itself is a result of mechanistically complex and interrelated processes that happen during the lifespan of the organism. Here, I propose to shift the focus from a systematic description and categorization of the hallmarks of aging to a model that separates the early, molecular origins of changes from cellular and tissue responses and represents the sequential and causative character of changes in aging. The proposed model aims to prompt discussion among the aging research community, guide future efforts in the field, and provide new ideas for investigation.
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    DOI 10.59368/agingbio.20230011
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  2. Article: Evolution of the enhancer-rich regulatory region of the gene for the cell-type specific transcription factor POU1F1.

    Wallis, Michael / Xu, Qianlan / Krawczyk, Michal / Skowronska-Krawczyk, Dorota

    Heliyon

    2024  Volume 10, Issue 7, Page(s) e28640

    Abstract: Precise spatio-temporal expression of genes in organogenesis is regulated by the coordinated interplay of DNA elements such as promoter and enhancers present in the regulatory region of a given locus. POU1F1 transcription factor plays a crucial role in ... ...

    Abstract Precise spatio-temporal expression of genes in organogenesis is regulated by the coordinated interplay of DNA elements such as promoter and enhancers present in the regulatory region of a given locus. POU1F1 transcription factor plays a crucial role in the development of somatotrophs, lactotrophs and thyrotrophs in the anterior pituitary gland, and in maintaining high expression of growth hormone, prolactin and TSH. In mouse, expression of
    Language English
    Publishing date 2024-03-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2024.e28640
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  3. Article ; Online: Dynamic Progress in Technological Advances to Study Lipids in Aging: Challenges and Future Directions.

    Gao, Fangyuan / Tom, Emily / Skowronska-Krawczyk, Dorota

    Frontiers in aging

    2022  Volume 3, Page(s) 851073

    Abstract: Lipids participate in all cellular processes. Diverse methods have been developed to investigate lipid composition and distribution in biological samples to understand the effect of lipids across an organism's lifespan. Here, we summarize the advanced ... ...

    Abstract Lipids participate in all cellular processes. Diverse methods have been developed to investigate lipid composition and distribution in biological samples to understand the effect of lipids across an organism's lifespan. Here, we summarize the advanced techniques for studying lipids, including mass spectrometry-based lipidomics, lipid imaging, chemical-based lipid analysis and lipid engineering and their advantages. We further discuss the limitation of the current methods to gain an in-depth knowledge of the role of lipids in aging, and the possibility of lipid-based therapy in aging-related diseases.
    Language English
    Publishing date 2022-03-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 3076785-4
    ISSN 2673-6217 ; 2673-6217
    ISSN (online) 2673-6217
    ISSN 2673-6217
    DOI 10.3389/fragi.2022.851073
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  4. Article ; Online: Editorial: Molecular Role of Lipids in Aging.

    Skowronska-Krawczyk, Dorota / Narayan, Priyanka / Tessarz, Peter

    Frontiers in aging

    2022  Volume 3, Page(s) 946884

    Language English
    Publishing date 2022-06-20
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 3076785-4
    ISSN 2673-6217 ; 2673-6217
    ISSN (online) 2673-6217
    ISSN 2673-6217
    DOI 10.3389/fragi.2022.946884
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  5. Article ; Online: Marking cell-type-restricted enhancers before their activation.

    Skowronska-Krawczyk, Dorota

    Cell cycle (Georgetown, Tex.)

    2018  Volume 17, Issue 13, Page(s) 1525–1526

    MeSH term(s) Embryonic Stem Cells ; Enhancer Elements, Genetic
    Language English
    Publishing date 2018-08-10
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.1080/15384101.2018.1491459
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5881: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Aging membranes: Unexplored functions for lipids in the lifespan of the central nervous system.

    Skowronska-Krawczyk, Dorota / Budin, Itay

    Experimental gerontology

    2019  Volume 131, Page(s) 110817

    Abstract: Lipids constitute a significant group of biological metabolites and the building blocks of all cell membranes. The abundance and stoichiometries of different lipid species are known to vary across the lifespan and metabolic state, yet the functional ... ...

    Abstract Lipids constitute a significant group of biological metabolites and the building blocks of all cell membranes. The abundance and stoichiometries of different lipid species are known to vary across the lifespan and metabolic state, yet the functional effects of these changes have been challenging to understand. Here we review the potentially powerful intersection of lipid metabolism, which determines membrane composition, and aging. We first introduce several key lipid classes that are associated with aging and aging-related disease, where they are found in organisms, and how they act on membrane structure and function. Instead of neutral lipids, which have primary roles in energy storage and homeostasis, we review known functions for polar lipids that control the physicochemical properties of cell membranes. We then focus on aging processes in the central nervous system (CNS), which is enriched in lipids and is highly dependent on membrane structure for function. Recent studies show how lipids act not just as biomarkers of aging and associated changes in the CNS, but as direct mediators of these processes. As a model system, we explore how fatty acid composition in the retina impact aging and aging-related disease. We propose that the biophysical effects of membrane structure on fundamental eukaryotic processes - mitochondrial respiration and autophagy - provide avenues by which lipid dysregulation can accelerate aging processes. Finally, we lay out ways in which an increased understanding of lipid membrane biology can be applied to studies of aging and lifespan.
    MeSH term(s) Aging/physiology ; Central Nervous System/physiology ; Humans ; Lipid Metabolism/physiology ; Retina/physiology
    Language English
    Publishing date 2019-12-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 390992-x
    ISSN 1873-6815 ; 0531-5565
    ISSN (online) 1873-6815
    ISSN 0531-5565
    DOI 10.1016/j.exger.2019.110817
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 579: 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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  7. Article: A novel quantification method for retinal pigment epithelium phagocytosis using a very-long-chain polyunsaturated fatty acids-based strategy.

    Gao, Fangyuan / Tom, Emily / Lieffrig, Stephanie A / Finnemann, Silvia C / Skowronska-Krawczyk, Dorota

    Frontiers in molecular neuroscience

    2023  Volume 16, Page(s) 1279457

    Abstract: Introduction: The vertebrate retinal pigment epithelium (RPE) lies adjacent to the photoreceptors and is responsible for the engulfment and degradation of shed photoreceptor outer segment fragments (POS) through receptor-mediated phagocytosis. ... ...

    Abstract Introduction: The vertebrate retinal pigment epithelium (RPE) lies adjacent to the photoreceptors and is responsible for the engulfment and degradation of shed photoreceptor outer segment fragments (POS) through receptor-mediated phagocytosis. Phagocytosis of POS is critical for maintaining photoreceptor function and is a key indicator of RPE functionality. Popular established methods to assess RPE phagocytosis rely mainly on quantifying POS proteins, especially their most abundant protein rhodopsin, or on fluorescent dye conjugation of bulk, unspecified POS components. While these approaches are practical and quantitative, they fail to assess the fate of POS lipids, which make up about 50% of POS by dry weight and whose processing is essential for life-long functionality of RPE and retina.
    Methods: We have developed a novel very-long-chain polyunsaturated fatty acids (VLC-PUFA)-based approach for evaluating RPE phagocytic activity by primary bovine and rat RPE and the human ARPE-19 cell line and validated its results using traditional methods.
    Results and discussion: This new approach can be used to detect
    Language English
    Publishing date 2023-10-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2023.1279457
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  8. Article: Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa.

    Moore, Spencer M / Skowronska-Krawczyk, Dorota / Chao, Daniel L

    Journal of clinical medicine

    2020  Volume 9, Issue 7

    Abstract: Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) with a prevalence of 1:4000, characterized by initial rod photoreceptor loss and subsequent cone photoreceptor loss with accompanying nyctalopia, visual field deficits, and visual acuity ... ...

    Abstract Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) with a prevalence of 1:4000, characterized by initial rod photoreceptor loss and subsequent cone photoreceptor loss with accompanying nyctalopia, visual field deficits, and visual acuity loss. A diversity of causative mutations have been described with autosomal dominant, autosomal recessive, and X-linked inheritance and sporadic mutations. The diversity of mutations makes gene therapy challenging, highlighting the need for mutation-agnostic treatments. Neural leucine zipper (NRL) and NR2E3 are factors important for rod photoreceptor cell differentiation and homeostasis. Germline mutations in NRL or NR2E3 leads to a loss of rods and an increased number of cones with short wavelength opsin in both rodents and humans. Multiple groups have demonstrated that inhibition of NRL or NR2E3 activity in the mature retina could endow rods with certain properties of cones, which prevents cell death in multiple rodent RP models with diverse mutations. In this review, we summarize the literature on NRL and NR2E3, therapeutic strategies of NRL/NR2E3 modulation in preclinical RP models, as well as future directions of research. In summary, inhibition of the NRL/NR2E3 pathway represents an intriguing mutation agnostic and disease-modifying target for the treatment of RP.
    Language English
    Publishing date 2020-07-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm9072224
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  9. Article ; Online: ELOVL2: Not just a biomarker of aging.

    Chao, Daniel L / Skowronska-Krawczyk, Dorota

    Translational medicine of aging

    2020  Volume 4, Page(s) 78–80

    Abstract: DNA methylation of the ELOVL2 (Elongation Of Very Long Chain Fatty Acids-Like 2) promoter is one of the most robust molecular biomarkers for chronological age, but whether ELOVL2 plays a functional role in aging has not been explored. ELOVL2 encodes a ... ...

    Abstract DNA methylation of the ELOVL2 (Elongation Of Very Long Chain Fatty Acids-Like 2) promoter is one of the most robust molecular biomarkers for chronological age, but whether ELOVL2 plays a functional role in aging has not been explored. ELOVL2 encodes a transmembrane protein involved in the synthesis of very long polyunsaturated fatty acids (VLC-PUFAs). These fatty acids play important roles in retinal biology and photoreceptor renewal, key processes implicated in age-related eye diseases such as age-related macular degeneration (AMD). Here, we summarize our work deciphering the role of ELOVL2 in the eye emphasizing the potential functional role of age-related DNA methylation in the pathophysiology of AMD.
    Language English
    Publishing date 2020-06-30
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2468-5011
    ISSN (online) 2468-5011
    DOI 10.1016/j.tma.2020.06.004
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  10. Article: Emerging Concepts for RNA Therapeutics for Inherited Retinal Disease.

    Moore, Spencer M / Skowronska-Krawczyk, Dorota / Chao, Daniel L

    Advances in experimental medicine and biology

    2020  Volume 1185, Page(s) 85–89

    Abstract: Inherited retinal diseases (IRD) encompass a wide spectrum of hereditary blindness with significant genetic heterogeneity. Therapeutics regulating gene expression on an RNA level have significant promise for treating IRD. In this review, we review the ... ...

    Abstract Inherited retinal diseases (IRD) encompass a wide spectrum of hereditary blindness with significant genetic heterogeneity. Therapeutics regulating gene expression on an RNA level have significant promise for treating IRD. In this review, we review the molecular basis of oligonucleotide therapeutics such as ribozymes, RNA interference (RNAi), antisense oligonucleotides (ASO), CRISPRi/a, and their applications to treatments of IRD.
    MeSH term(s) Clustered Regularly Interspaced Short Palindromic Repeats ; Humans ; Oligonucleotides, Antisense/therapeutic use ; RNA/therapeutic use ; RNA Interference ; RNA, Catalytic/therapeutic use ; Retinal Diseases/therapy
    Chemical Substances Oligonucleotides, Antisense ; RNA, Catalytic ; RNA (63231-63-0)
    Language English
    Publishing date 2020-01-22
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-27378-1_14
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