bims-minfam 2024-12-22 papers

Issue of 2024–12–22
six papers selected by
Ayesh Seneviratne, McMaster University

Nature. 2024 Dec 18.

A bile acid could explain how calorie restriction slows ageing.

David A Sinclair.

Keywords: Ageing; Metabolism; Microbiome; Nutrition

DOI: https://doi.org/10.1038/d41586-024-04062-1

Subcell Biochem. 2024 ;107 91-116

Unlocking the Potential of Senolytic Compounds: Advancements, Opportunities, and Challenges in Ageing-Related Research.

Lilian Sales Gomez, Diana Jurk.

Cellular senescence is recognised as a contributor to the ageing process and the development of multiple age-related conditions. Researchers have launched efforts to identify compounds capable to selectively kill senescent cells, known as senolytics, without affecting non senescent cells. As of now, over 40 compounds have demonstrated senolytic properties, offering promising prospects for reversing or ameliorating age-related conditions in preclinical studies.This chapter presents the most recent developments in senolytic drug research, encompassing investigations spanning basic science, preclinical trials, and clinical studies. While many of these investigations have generated encouraging results in the realm of age-related interventions, this chapter also addresses potential challenges and pitfalls.

Keywords: Age-related diseases; Ageing; Cellular senescence; Senolytic

DOI: https://doi.org/10.1007/978-3-031-66768-8_5

Cancers (Basel). 2024 Dec 09. pii: 4118. [Epub ahead of print]16(23):

Implications of Clonal Hematopoiesis in Hematological and Non-Hematological Disorders.

Qi Zhang, Rita Yim, Paul Lee, Lynn Chin, Vivian Li, Harinder Gill.

Clonal hematopoiesis (CH) is associated with an increased risk of developing myeloid neoplasms (MNs) such as myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). In general, CH comprises clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). It is an age-related phenomenon characterized by the presence of somatic mutations in hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells (HSPCs) that acquire a fitness advantage under selection pressure. Individuals with CHIP have an absolute risk of 0.5-1.0% per year for progressing to MDS or AML. Inflammation, smoking, cytotoxic therapy, and radiation can promote the process of clonal expansion and leukemic transformation. Of note, exposure to chemotherapy or radiation for patients with solid tumors or lymphomas can increase the risk of therapy-related MN. Beyond hematological malignancies, CH also serves as an independent risk factor for heart disease, stroke, chronic obstructive pulmonary disease, and chronic kidney disease. Prognostic models such as the CH risk score and MN-prediction models can provide a framework for risk stratification and clinical management of CHIP/CCUS and identify high-risk individuals who may benefit from close surveillance. For CH or related disorders, therapeutic strategies targeting specific CH-associated mutations and specific selection pressure may have a potential role in the future.

Keywords: acute myeloid leukemia; clonal cytopenia of undetermined significance; clonal hematopoiesis; clonal hematopoiesis of indeterminate potential; myelodysplastic neoplasm

DOI: https://doi.org/10.3390/cancers16234118

Cancers (Basel). 2024 Nov 27. pii: 3974. [Epub ahead of print]16(23):

Inflammation and Related Signaling Pathways in Acute Myeloid Leukemia.

Nour Sabiha Naji, Mrudula Sathish, Theodoros Karantanos.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, and inflammatory signaling is involved in its pathogenesis. Cytokines exert a robust effect on the progression of AML and affect survival outcomes. The dysregulation in the cytokine network may foster a pro-tumorigenic microenvironment, increasing leukemic cell proliferation, decreasing survival and driving drug resistance. The dominance of pro-inflammatory mediators such as IL-11β, TNF-α and IL-6 over anti-inflammatory mediators such as TGF-β and IL-10 has been implicated in tumor progression. Additionally, inflammatory cytokines have favored certain populations of hematopoietic stem and progenitor cells with mutated clonal hematopoiesis genes. This article summarizes current knowledge about inflammatory cytokines and signaling pathways in AML, their modes of action and the implications for immune tolerance and clonal hematopoiesis, with the aim of finding potential therapeutic interventions to improve clinical outcomes in AML patients.

Keywords: acute myeloid leukemia; clonal hematopoiesis; immune tolerance; inflammation

DOI: https://doi.org/10.3390/cancers16233974

Nature. 2024 Dec 19.

A blood test detects aged cells.

Keywords: Ageing

DOI: https://doi.org/10.1038/d41586-024-04172-w