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Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions.

ABSTRACT: Cellular senescence refers to a cellular phenotype characterized by an altered transcriptome, pro-inflammatory secretome, and generally irreversible growth arrest. Acutely senescent cells are widely recognized as performing key physiological functions in vivo promoting normal organogenesis, successful wound repair, and cancer defense. In contrast, the accumulation of chronically senescent cells in response to aging, cell stress, genotoxic damage, and other injurious stimuli is increasingly recognized as an important contributor to organ dysfunction, tissue fibrosis, and the more generalized aging phenotype. In this review, we summarize our current knowledge of the role of senescent cells in promoting progressive fibrosis and dysfunction with a particular focus on the kidney and reference to other organ systems. Specific differences between healthy and senescent cells are reviewed along with a summary of several experimental pharmacological approaches to deplete or manipulate senescent cells to preserve organ integrity and function with aging and after injury. Finally, key questions for future research and clinical translation are discussed.

SUBMITTER: Docherty MH

PROVIDER: S-EPMC7264097 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions.

Docherty Marie Helena MH Baird David P DP Hughes Jeremy J Ferenbach David A DA

Frontiers in pharmacology 20200526

Cellular senescence refers to a cellular phenotype characterized by an altered transcriptome, pro-inflammatory secretome, and generally irreversible growth arrest. Acutely senescent cells are widely recognized as performing key physiological functions <i>in vivo</i> promoting normal organogenesis, successful wound repair, and cancer defense. In contrast, the accumulation of chronically senescent cells in response to aging, cell stress, genotoxic damage, and other injurious stimuli is increasingl ...[more]

PMID: 32528288

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Project description:BackgroundCurrent evidence-based treatments for adult anorexia nervosa (AN) have limitations, with high attrition, very poor outcomes for 20% of people, and no clearly superior manualised therapy for adults with AN. Specialist Supportive Clinical Management (SSCM) was designed as a control treatment but has evolved as a valid first line treatment. The present paper aims to provide an overview of the evidence base for SSCM and a pedagogical reconceptualization with expansion by theoretical integration (TI). BODY: A secondary meta-analysis endorses SSCM as a promising treatment. This paper positions SSCM as a manualised therapy for adult AN with six unique features, namely (1) a philosophy which is person-centred, non-prescriptive, and informed by the person's strengths and values, (2) a focus on the person through inclusion of supportive psychotherapy and problem (clinical management), within target symptoms as defined in relation to AN, (3) a flexible and responsive therapy that could be delivered by a variety of clinicians with experience treating AN (4) a commitment to reversing starvation though a directional approach and a defined yet flexible stance on dietetic intervention (5) a commitment to the therapeutic relationship within all three phases of treatment, and (6) a therapy 'uncluttered' by specific mandates. In addition, this paper positions SSCM as a treatment that may be strengthened by other modalities and may also be adapted to the treatment of other eating disorders (ED), not just AN. The level of therapist sophistication to deliver upon the supportive psychotherapy component is explored and future directions are offered.ConclusionSSCM is a unique and valid first line treatment for AN and would benefit from further expansion in line with emerging understandings of AN to strengthen it as a treatment. Speculation on aspects of potency would benefit from further testing. The proposed re-conceptualisation of SSCM in the context of its evidence may strengthen it as a treatment overall, position it as adaptable for treatment of other eating disorders and make it more accessible to clinicians.

Dataset Information

Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions.

Publications

Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions.

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