bims-minfam 2024-09-29 papers

Issue of 2024–09–29
five papers selected by
Ayesh Seneviratne, Western University

Kidney Int. 2024 Oct;pii: S0085-2538(24)00462-9. [Epub ahead of print]106(4): 554-556

Elucidating the role of clonal hematopoiesis in acute kidney injury.

Keywords: acute kidney injury; aging; clonal hematopoiesis of indeterminate potential; inflammation

DOI: https://doi.org/10.1016/j.kint.2024.06.017

Nat Aging. 2024 Sep 23.

Probabilistic inference of epigenetic age acceleration from cellular dynamics.

Jan K Dabrowski, Emma J Yang, Samuel J C Crofts, Robert F Hillary, Daniel J Simpson, Daniel L McCartney, Riccardo E Marioni, Kristina Kirschner, Eric Latorre-Crespo, Tamir Chandra.

The emergence of epigenetic predictors was a pivotal moment in geroscience, propelling the measurement and concept of biological aging into a quantitative era; however, while current epigenetic clocks show strong predictive power, they are data-driven in nature and are not based on the underlying biological mechanisms driving methylation dynamics. We show that predictions of these clocks are susceptible to several confounding non-age-related phenomena that make interpretation of these estimates and associations difficult. To address these limitations, we developed a probabilistic model describing methylation transitions at the cellular level. Our approach reveals two measurable components, acceleration and bias, which directly reflect perturbations of the underlying cellular dynamics. Acceleration is the proportional increase in the speed of methylation transitions across CpG sites, whereas bias corresponds to global changes in methylation levels. Using data from 15,900 participants from the Generation Scotland study, we develop a robust inference framework and show that these are two distinct processes confounding current epigenetic predictors. Our results show improved associations of acceleration and bias with physiological traits known to impact healthy aging, such as smoking and alcohol consumption, respectively. Furthermore, a genome-wide association study of epigenetic age acceleration identified seven genomic loci.

DOI: https://doi.org/10.1038/s43587-024-00700-5

Mech Ageing Dev. 2024 Sep 20. pii: S0047-6374(24)00093-9. [Epub ahead of print]222 111993

The role of mitochondria in cytokine and chemokine signalling during ageing.

Maria Kalykaki, Teresa Rubio-Tomás, Nektarios Tavernarakis.

Ageing is accompanied by a persistent, low-level inflammation, termed "inflammageing", which contributes to the pathogenesis of age-related diseases. Mitochondria fulfil multiple roles in host immune responses, while mitochondrial dysfunction, a hallmark of ageing, has been shown to promote chronic inflammatory states by regulating the production of cytokines and chemokines. In this review, we aim to disentangle the molecular mechanisms underlying this process. We describe the role of mitochondrial signalling components such as mitochondrial DNA, mitochondrial RNA, N-formylated peptides, ROS, cardiolipin, cytochrome c, mitochondrial metabolites, potassium efflux and mitochondrial calcium in the age-related immune system activation. Furthermore, we discuss the effect of age-related decline in mitochondrial quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy and UPRmt, in inflammatory states upon ageing. In addition, we focus on the dynamic relationship between mitochondrial dysfunction and cellular senescence and its role in regulating the secretion of pro-inflammatory molecules by senescent cells. Finally, we review the existing literature regarding mitochondrial dysfunction and inflammation in specific age-related pathological conditions, including neurodegenerative diseases (Alzheimer's and Parkinson's disease, and amyotrophic lateral sclerosis), osteoarthritis and sarcopenia.

Keywords: Age-related disease; Chemokine; Cytokine; Inflammageing; Mitochondrial dysfunction; Senescence

DOI: https://doi.org/10.1016/j.mad.2024.111993