ESPEYB18 14. Medicine and Science (1) (14 abstracts)
14.11. Ageing hallmarks exhibit organ-specific temporal signatures
Nicholas Schaum , Benoit Lehallier , Oliver Hahn , Róbert Pálovics , Shayan Hosseinzadeh , Song E Lee , Rene Sit , Davis P Lee , Patricia Morán Losada , Macy E Zardeneta , Tobias Fehlmann , James T Webber , Aaron McGeever , Kruti Calcuttawala , Hui Zhang , Daniela Berdnik , Vidhu Mathur , Weilun Tan , Alexander Zee , Michelle Tan , The Tabula Muris Consortium , Angela Oliveira Pisco , Jim Karkanias , Norma F Neff , Andreas Keller , Spyros Darmanis , Stephen R Quake & Tony Wyss-Coray
Nature 2020; 583: 596–602https://www.nature.com/articles/s41586-020-2499-y
In order to understand the cellular processes that underlie ageing, the authors performed plasma proteomics at 10 different ages across the lifespan of the mouse. They integrated these data with a parallel large study published alongside this paper in the same edition (1), which describes the ‘Mouse Ageing Cell Atlas’, a single-cell transcriptomic atlas that characterizes changes in gene expression with age across 23 tissues. Together, the data reveal clustered patterns of changes (‘trajectory groups’) in gene expression and protein levels, consistent with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, circadian rhythm, and inflammatory and immune response.
One of these clustered ageing trajectories is an extensive immune cell activation, which is first detectable in white adipose tissue depots during middle age, and involves the accumulation of T cells and B cells in adipose tissue. Notably, many of these trajectory groups showed similar expression patterns across tissues, although with some differences in amplitude and timing, and these changes could be correlated with protein levels in plasma. Hence, potentially future plasma proteomic profiling could give insights into disordered ageing across several tissues.
The authors conclude that these data identify a coordinated yet often asynchronous inter- and intra-organ ageing process. The findings highlight biological processes that deserve renewed focus as mechanisms of ageing, such as immune cell activation, circadian rhythm disruption, and adipose tissue decline. The study also provides rich data on biomarkers to monitor the effects of rejuvenation strategies under current investigation, such as the removal of senescent cells and reducing nutrient sensing (e.g. using rapamycin and metformin).
Reference: 1. The Tabula Muris Consortium. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. Nature 2020; 583: 590–595.
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