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  1. Article ; Online: The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases.

    Salminen, Antero

    Journal of molecular medicine (Berlin, Germany)

    2024  

    Abstract: The accumulation of senescent cells within tissues is a hallmark of the aging process. Senescent cells are also commonly present in many age-related diseases and in the cancer microenvironment. The escape of abnormal cells from immune surveillance ... ...

    Abstract The accumulation of senescent cells within tissues is a hallmark of the aging process. Senescent cells are also commonly present in many age-related diseases and in the cancer microenvironment. The escape of abnormal cells from immune surveillance indicates that there is some defect in the function of cytotoxic immune cells, e.g., CD8
    Language English
    Publishing date 2024-04-11
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1223802-8
    ISSN 1432-1440 ; 0946-2716
    ISSN (online) 1432-1440
    ISSN 0946-2716
    DOI 10.1007/s00109-024-02444-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The role of immunosuppressive myofibroblasts in the aging process and age-related diseases.

    Salminen, Antero

    Journal of molecular medicine (Berlin, Germany)

    2023  Volume 101, Issue 10, Page(s) 1169–1189

    Abstract: Tissue-resident fibroblasts are mesenchymal cells which control the structural integrity of the extracellular matrix (ECM). Fibroblasts possess a remarkable plasticity to allow them to adapt to the changes in the microenvironment and thus maintain tissue ...

    Abstract Tissue-resident fibroblasts are mesenchymal cells which control the structural integrity of the extracellular matrix (ECM). Fibroblasts possess a remarkable plasticity to allow them to adapt to the changes in the microenvironment and thus maintain tissue homeostasis. Several stresses, also those associated with the aging process, convert quiescent fibroblasts into myofibroblasts which not only display fibrogenic properties but also act as immune regulators cooperating both with tissue-resident immune cells and those immune cells recruited into affected tissues. TGF-β cytokine and reactive oxygen species (ROS) are major inducers of myofibroblast differentiation in pathological conditions either from quiescent fibroblasts or via transdifferentiation from certain other cell types, e.g., macrophages, adipocytes, pericytes, and endothelial cells. Intriguingly, TGF-β and ROS are also important signaling mediators between immunosuppressive cells, such as MDSCs, Tregs, and M2 macrophages. It seems that in pathological states, myofibroblasts are able to interact with the immunosuppressive network. There is clear evidence that a low-grade chronic inflammatory state in aging tissues is counteracted by activation of compensatory immunosuppression. Interestingly, common enhancers of the aging process, such as oxidative stress, loss of DNA integrity, and inflammatory insults, are inducers of myofibroblasts, whereas anti-aging treatments with metformin and rapamycin suppress the differentiation of myofibroblasts and thus prevent age-related tissue fibrosis. I will examine the reciprocal interactions between myofibroblasts and immunosuppressive cells within aging tissues. It seems that the differentiation of myofibroblasts with age-related harmful stresses enhances the activity of the immunosuppressive network which promotes tissue fibrosis and degeneration in elderly individuals.
    Language English
    Publishing date 2023-08-22
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1223802-8
    ISSN 1432-1440 ; 0946-2716
    ISSN (online) 1432-1440
    ISSN 0946-2716
    DOI 10.1007/s00109-023-02360-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: AMPK signaling inhibits the differentiation of myofibroblasts: impact on age-related tissue fibrosis and degeneration.

    Salminen, Antero

    Biogerontology

    2023  Volume 25, Issue 1, Page(s) 83–106

    Abstract: Disruption of the extracellular matrix (ECM) and an accumulation of fibrotic lesions within tissues are two of the distinctive hallmarks of the aging process. Tissue fibroblasts are mesenchymal cells which display an impressive plasticity in the ... ...

    Abstract Disruption of the extracellular matrix (ECM) and an accumulation of fibrotic lesions within tissues are two of the distinctive hallmarks of the aging process. Tissue fibroblasts are mesenchymal cells which display an impressive plasticity in the regulation of ECM integrity and thus on tissue homeostasis. Single-cell transcriptome studies have revealed that tissue fibroblasts exhibit a remarkable heterogeneity with aging and in age-related diseases. Excessive stress and inflammatory insults induce the differentiation of fibroblasts into myofibroblasts which are fusiform contractile cells and abundantly secrete the components of the ECM and proteolytic enzymes as well as many inflammatory mediators. Detrimental stresses can also induce the transdifferentiation of certain mesenchymal and myeloid cells into myofibroblasts. Interestingly, many age-related stresses, such as oxidative and endoplasmic reticulum stresses, ECM stiffness, inflammatory mediators, telomere shortening, and several alarmins from damaged cells are potent inducers of myofibroblast differentiation. Intriguingly, there is convincing evidence that the signaling pathways stimulated by the AMP-activated protein kinase (AMPK) are potent inhibitors of myofibroblast differentiation and accordingly AMPK signaling reduces fibrotic lesions within tissues, e.g., in age-related cardiac and pulmonary fibrosis. AMPK signaling is not only an important regulator of energy metabolism but it is also able to control cell fate determination and many functions of the immune system. It is known that AMPK signaling can delay the aging process via an integrated signaling network. AMPK signaling inhibits myofibroblast differentiation, e.g., by suppressing signaling through the TGF-β, NF-κB, STAT3, and YAP/TAZ pathways. It seems that AMPK signaling can alleviate age-related tissue fibrosis and degeneration by inhibiting the differentiation of myofibroblasts.
    MeSH term(s) Humans ; Myofibroblasts/metabolism ; Myofibroblasts/pathology ; AMP-Activated Protein Kinases/metabolism ; Signal Transduction ; Cell Differentiation ; Fibroblasts ; Fibrosis ; Inflammation Mediators ; Transforming Growth Factor beta1/metabolism
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31) ; Inflammation Mediators ; Transforming Growth Factor beta1
    Language English
    Publishing date 2023-11-02
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2047160-9
    ISSN 1573-6768 ; 1389-5729
    ISSN (online) 1573-6768
    ISSN 1389-5729
    DOI 10.1007/s10522-023-10072-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The plasticity of fibroblasts: A forgotten player in the aging process.

    Salminen, Antero

    Ageing research reviews

    2023  Volume 89, Page(s) 101995

    Abstract: Tissue-resident fibroblasts are mesenchymal cells which possess an impressive plasticity in their ability to modify their properties according to the requirements of the microenvironment. There are diverse subgroups of fibroblast phenotypes associated ... ...

    Abstract Tissue-resident fibroblasts are mesenchymal cells which possess an impressive plasticity in their ability to modify their properties according to the requirements of the microenvironment. There are diverse subgroups of fibroblast phenotypes associated with different tissue pathological conditions, e.g., cancers, wound healing, and many fibrotic and inflammatory conditions. The heterogeneous phenotypes can be subdivided into fibrogenic and non-fibrogenic, inflammatory and immunosuppressive subtypes as well as cellular senescent subsets. A major hallmark of activated fibroblasts is that they contain different amounts of stress fibers combined with α-smooth muscle actin (α-SMA) protein, i.e., commonly this phenotype has been called the myofibroblast. Interestingly, several stresses associated with the aging process are potent inducers of myofibroblast differentiation, e.g., oxidative and endoplasmic reticulum stresses, extracellular matrix (ECM) disorders, inflammatory mediators, and telomere shortening. Accordingly, anti-aging treatments with metformin and rapamycin inhibited the differentiation of myofibroblasts in tissues. There is evidence that the senescent phenotype induced in cultured fibroblasts does not represent the phenotype of fibroblasts in aged tissues. Considering the versatile plasticity of fibroblasts as well as their frequency and structural importance in tissues, it does seem that fibroblasts are overlooked players in the aging process.
    MeSH term(s) Humans ; Fibroblasts/metabolism ; Myofibroblasts/metabolism ; Myofibroblasts/pathology ; Cell Differentiation/physiology ; Wound Healing/physiology ; Cellular Senescence ; Cells, Cultured
    Language English
    Publishing date 2023-06-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2075672-0
    ISSN 1872-9649 ; 1568-1637
    ISSN (online) 1872-9649
    ISSN 1568-1637
    DOI 10.1016/j.arr.2023.101995
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  5. Article ; Online: Aryl hydrocarbon receptor (AhR) impairs circadian regulation: Impact on the aging process.

    Salminen, Antero

    Ageing research reviews

    2023  Volume 87, Page(s) 101928

    Abstract: Circadian clocks control the internal sleep-wake rhythmicity of 24 h which is synchronized by the solar cycle. Circadian regulation of metabolism evolved about 2.5 billion years ago, i.e., the rhythmicity has been conserved from cyanobacteria and Archaea ...

    Abstract Circadian clocks control the internal sleep-wake rhythmicity of 24 h which is synchronized by the solar cycle. Circadian regulation of metabolism evolved about 2.5 billion years ago, i.e., the rhythmicity has been conserved from cyanobacteria and Archaea through to mammals although the mechanisms utilized have developed with evolution. While the aryl hydrocarbon receptor (AhR) is an evolutionarily conserved defence mechanism against environmental threats, it has gained many novel functions during evolution, such as the regulation of cell cycle, proteostasis, and many immune functions. There is robust evidence that AhR signaling impairs circadian rhythmicity, e.g., by interacting with the core BMAL1/CLOCK complex and disturbing the epigenetic regulation of clock genes. The maintenance of circadian rhythms is impaired with aging, disturbing metabolism and many important functions in aged organisms. Interestingly, it is known that AhR signaling promotes an age-related tissue degeneration, e.g., it is able to inhibit autophagy, enhance cellular senescence, and disrupt extracellular matrix. These alterations are rather similar to those induced by a long-term impairment of circadian rhythms. However, it is not known whether AhR signaling enhances the aging process by impairing circadian homeostasis. I will examine the experimental evidence indicating that AhR signaling is able to promote the age-related degeneration via a disruption of circadian rhythmicity.
    MeSH term(s) Animals ; Humans ; Aged ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Epigenesis, Genetic ; Circadian Rhythm/physiology ; Circadian Clocks/genetics ; Aging/genetics ; Mammals/metabolism
    Chemical Substances Receptors, Aryl Hydrocarbon
    Language English
    Publishing date 2023-04-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2075672-0
    ISSN 1872-9649 ; 1568-1637
    ISSN (online) 1872-9649
    ISSN 1568-1637
    DOI 10.1016/j.arr.2023.101928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Activation of aryl hydrocarbon receptor (AhR) in Alzheimer's disease: role of tryptophan metabolites generated by gut host-microbiota.

    Salminen, Antero

    Journal of molecular medicine (Berlin, Germany)

    2023  Volume 101, Issue 3, Page(s) 201–222

    Abstract: Gut microbiota in interaction with intestinal host tissues influences many brain functions and microbial dysbiosis has been linked with brain disorders, such as neuropsychiatric conditions and Alzheimer's disease (AD). L-tryptophan metabolites and short- ... ...

    Abstract Gut microbiota in interaction with intestinal host tissues influences many brain functions and microbial dysbiosis has been linked with brain disorders, such as neuropsychiatric conditions and Alzheimer's disease (AD). L-tryptophan metabolites and short-chained fatty acids (SCFA) are major messengers in the microbiota-brain axis. Aryl hydrocarbon receptors (AhR) are main targets of tryptophan metabolites in brain microvessels which possess an enriched expression of AhR protein. The Ah receptor is an evolutionarily conserved, ligand-activated transcription factor which is not only a sensor of xenobiotic toxins but also a pleiotropic regulator of both developmental processes and age-related tissue degeneration. Major microbiota-produced tryptophan metabolites involve indole derivatives, e.g., indole 3-pyruvic acid, indole 3-acetaldehyde, and indoxyl sulfate, whereas indoleamine and tryptophan 2,3-dioxygenases (IDO/TDO) of intestine host cells activate the kynurenine (KYN) pathway generating KYN metabolites, many of which are activators of AhR signaling. Chronic kidney disease (CKD) increases the serum level of indoxyl sulfate which promotes AD pathogenesis, e.g., it disrupts integrity of blood-brain barrier (BBB) and impairs cognitive functions. Activation of AhR signaling disturbs vascular homeostasis in brain; (i) it controls blood flow via the renin-angiotensin system, (ii) it inactivates endothelial nitric oxide synthase (eNOS), thus impairing NO production and vasodilatation, and (iii) it induces oxidative stress, stimulates inflammation, promotes cellular senescence, and enhances calcification of vascular walls. All these alterations are evident in cerebral amyloid angiopathy (CAA) in AD pathology. Moreover, AhR signaling can disturb circadian regulation and probably affect glymphatic flow. It seems plausible that dysbiosis of gut microbiota impairs the integrity of BBB via the activation of AhR signaling and thus aggravates AD pathology. KEY MESSAGES: Dysbiosis of gut microbiota is associated with dementia and Alzheimer's disease. Tryptophan metabolites are major messengers from the gut host-microbiota to brain. Tryptophan metabolites activate aryl hydrocarbon receptor (AhR) signaling in brain. The expression of AhR protein is enriched in brain microvessels and blood-brain barrier. Tryptophan metabolites disturb brain vascular integrity via AhR signaling. Dysbiosis of gut microbiota promotes inflammation and AD pathology via AhR signaling.
    MeSH term(s) Humans ; Gastrointestinal Microbiome ; Receptors, Aryl Hydrocarbon/metabolism ; Indican ; Tryptophan/metabolism ; Alzheimer Disease ; Dysbiosis ; Indoles ; Microbiota ; Inflammation
    Chemical Substances Receptors, Aryl Hydrocarbon ; Indican (N187WK1Y1J) ; Tryptophan (8DUH1N11BX) ; Indoles
    Language English
    Publishing date 2023-02-09
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1223802-8
    ISSN 1432-1440 ; 0946-2716
    ISSN (online) 1432-1440
    ISSN 0946-2716
    DOI 10.1007/s00109-023-02289-5
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  7. Article ; Online: Clinical perspectives on the age-related increase of immunosuppressive activity.

    Salminen, Antero

    Journal of molecular medicine (Berlin, Germany)

    2022  Volume 100, Issue 5, Page(s) 697–712

    Abstract: The aging process is associated with a remodeling of the immune system involving chronic low-grade inflammation and a gradual decline in the function of the immune system. These processes are also called inflammaging and immunosenescence. The age-related ...

    Abstract The aging process is associated with a remodeling of the immune system involving chronic low-grade inflammation and a gradual decline in the function of the immune system. These processes are also called inflammaging and immunosenescence. The age-related immune remodeling is associated with many clinical changes, e.g., risk for cancers and chronic infections increases, whereas the efficiency of vaccination and immunotherapy declines with aging. On the other hand, there is convincing evidence that chronic inflammatory states promote the premature aging process. The inflammation associated with aging or chronic inflammatory conditions stimulates a counteracting immunosuppression which protects tissues from excessive inflammatory injuries but promotes immunosenescence. Immunosuppression is a driving force in tumors and chronic infections and it also induces the tolerance to vaccination and immunotherapies. Immunosuppressive cells, e.g., myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and type M2 macrophages, have a crucial role in tumorigenesis and chronic infections as well as in the tolerance to vaccination and immunotherapies. Interestingly, there is substantial evidence that inflammaging is also associated with an increased immunosuppressive activity, e.g., upregulation of immunosuppressive cells and anti-inflammatory cytokines. Given that both the aging and chronic inflammatory states involve the activation of immunosuppression and immunosenescence, this might explain why aging is a risk factor for tumorigenesis and chronic inflammatory states and conversely, chronic inflammatory insults promote the premature aging process in humans.
    MeSH term(s) Aging ; Aging, Premature ; Carcinogenesis ; Humans ; Immunosenescence ; Immunosuppressive Agents/therapeutic use ; Inflammation ; Neoplasms/etiology
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2022-04-06
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1223802-8
    ISSN 1432-1440 ; 0946-2716
    ISSN (online) 1432-1440
    ISSN 0946-2716
    DOI 10.1007/s00109-022-02193-4
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  8. Article ; Online: Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process.

    Salminen, Antero

    Cellular and molecular life sciences : CMLS

    2022  Volume 79, Issue 9, Page(s) 489

    Abstract: The antagonistic pleiotropy hypothesis is a well-known evolutionary theory to explain the aging process. It proposes that while a particular gene may possess beneficial effects during development, it can exert deleterious properties in the aging process. ...

    Abstract The antagonistic pleiotropy hypothesis is a well-known evolutionary theory to explain the aging process. It proposes that while a particular gene may possess beneficial effects during development, it can exert deleterious properties in the aging process. The aryl hydrocarbon receptor (AhR) has a significant role during embryogenesis, but later in life, it promotes several age-related degenerative processes. For instance, AhR factor (i) controls the pluripotency of stem cells and the stemness of cancer stem cells, (ii) it enhances the differentiation of embryonal stem cells, especially AhR signaling modulates the differentiation of hematopoietic stem cells and progenitor cells, (iii) it also stimulates the differentiation of immunosuppressive Tregs, Bregs, and M2 macrophages, and finally, (iv) AhR signaling participates in the differentiation of many peripheral tissues. On the other hand, AhR signaling is involved in many processes promoting cellular senescence and pathological processes, e.g., osteoporosis, vascular dysfunction, and the age-related remodeling of the immune system. Moreover, it inhibits autophagy and aggravates extracellular matrix degeneration. AhR signaling also stimulates oxidative stress, promotes excessive sphingolipid synthesis, and disturbs energy metabolism by catabolizing NAD
    MeSH term(s) Epigenesis, Genetic ; NF-kappa B/metabolism ; Receptors, Aryl Hydrocarbon/metabolism ; Signal Transduction/genetics
    Chemical Substances NF-kappa B ; Receptors, Aryl Hydrocarbon
    Language English
    Publishing date 2022-08-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04520-x
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  9. Article ; Online: Role of indoleamine 2,3-dioxygenase 1 (IDO1) and kynurenine pathway in the regulation of the aging process.

    Salminen, Antero

    Ageing research reviews

    2022  Volume 75, Page(s) 101573

    Abstract: Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states, e.g., in the aging process and age-related diseases. IDO1 enzyme catabolizes L-tryptophan (L-Trp) into kynurenine (KYN) thus stimulating the KYN pathway. The depletion of L- ...

    Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states, e.g., in the aging process and age-related diseases. IDO1 enzyme catabolizes L-tryptophan (L-Trp) into kynurenine (KYN) thus stimulating the KYN pathway. The depletion of L-Trp inhibits the proliferation of immune cells in inflamed tissues and it also reduces serotonin synthesis predisposing to psychiatric disorders. Interestingly, IDO1 protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIM) which trigger suppressive signaling through the binding of PI3K p110 and SHP-1 proteins. This immunosuppressive activity is not dependent on the catalytic activity of IDO1. KYN and its metabolite, kynurenic acid (KYNA), are potent activators of the aryl hydrocarbon receptor (AhR) which can enhance immunosuppression. IDO1-KYN-AhR signaling counteracts excessive pro-inflammatory responses in acute inflammation but in chronic inflammatory states it has many harmful effects. A chronic low-grade inflammation is associated with the aging process, a state called inflammaging. There is substantial evidence that the activation of the IDO1-KYN-AhR pathway robustly increases with the aging process. The activation of IDO1-KYN-AhR signaling does not only suppress the functions of effector immune cells, probably promoting immunosenescence, but it also impairs autophagy, induces cellular senescence, and remodels the extracellular matrix as well as enhancing the development of osteoporosis and vascular diseases. I will review the function of IDO1-KYN-AhR signaling and discuss its activation with aging as an enhancer of the aging process.
    MeSH term(s) Aging ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Inflammation ; Kynurenine/metabolism ; Tryptophan/metabolism
    Chemical Substances IDO1 protein, human ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Kynurenine (343-65-7) ; Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2022-01-24
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2075672-0
    ISSN 1872-9649 ; 1568-1637
    ISSN (online) 1872-9649
    ISSN 1568-1637
    DOI 10.1016/j.arr.2022.101573
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  10. Article ; Online: Mutual antagonism between aryl hydrocarbon receptor and hypoxia-inducible factor-1α (AhR/HIF-1α) signaling: Impact on the aging process.

    Salminen, Antero

    Cellular signalling

    2022  Volume 99, Page(s) 110445

    Abstract: The ambient oxygen level, many environmental toxins, and the rays of ultraviolet light (UV) provide a significant risk for the maintenance of organismal homeostasis. The aryl hydrocarbon receptors (AhR) represent a complex sensor system not only for ... ...

    Abstract The ambient oxygen level, many environmental toxins, and the rays of ultraviolet light (UV) provide a significant risk for the maintenance of organismal homeostasis. The aryl hydrocarbon receptors (AhR) represent a complex sensor system not only for environmental toxins and UV radiation but also for many endogenous ligands, e.g., L-tryptophan metabolites. The AhR signaling system is evolutionarily conserved and AhR homologs existed as many as 600 million years ago. The ancient atmosphere demanded the evolution of an oxygen-sensing system, i.e., hypoxia-inducible transcription factors (HIF) and their prolyl hydroxylase regulators (PHD). Given that both signaling systems have important roles in embryogenesis, it seems that they have been involved in the evolution of multicellular organisms. The evolutionary origin of the aging process is unknown although it is most likely associated with the evolution of multicellularity. Intriguingly, there is compelling evidence that while HIF-1α signaling extends the lifespan, that of AhR promotes many age-related degenerative processes, e.g., it increases oxidative stress, inhibits autophagy, promotes cellular senescence, and aggravates extracellular matrix degeneration. In contrast, HIF-1α signaling stimulates autophagy, inhibits cellular senescence, and enhances cell proliferation. Interestingly, there is a clear antagonism between the AhR and HIF-1α signaling pathways. For instance, (i) AhR and HIF-1α factors heterodimerize with the same factor, ARNT/HIF-1β, leading to their competition for DNA-binding, (ii) AhR and HIF-1α signaling exert antagonistic effects on autophagy, and (iii) co-chaperone p23 exhibits specific functions in the signaling of AhR and HIF-1α factors. One might speculate that it is the competition between the AhR and HIF-1α signaling pathways that is a driving force in the aging process.
    MeSH term(s) DNA ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Oxygen ; Prolyl Hydroxylases ; Pyridinolcarbamate ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Tryptophan
    Chemical Substances Hypoxia-Inducible Factor 1, alpha Subunit ; Receptors, Aryl Hydrocarbon ; Pyridinolcarbamate (81R511UV73) ; Tryptophan (8DUH1N11BX) ; DNA (9007-49-2) ; Prolyl Hydroxylases (EC 1.14.11.-) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 1002702-6
    ISSN 1873-3913 ; 0898-6568
    ISSN (online) 1873-3913
    ISSN 0898-6568
    DOI 10.1016/j.cellsig.2022.110445
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