Revealing a Master Controller of Development and Ageing PDF

Revealing a master controller of development and ageing Image: Adobe. 8 July 2024 University of Queensland researchers have unlocked crucial molecular secrets of ageing in cells, potentially paving the way to improve quality of life as people age. The study decoded the process by which genes regu...

Revealing a master controller of development and ageing Image: Adobe. 8 July 2024 University of Queensland researchers have unlocked crucial molecular secrets of ageing in cells, potentially paving the way to improve quality of life as people age. The study decoded the process by which genes regulate how people mature as they grow and age, and was led by Dr Christian Nefzger (https://imb.uq.edu.au/research-groups/nefzger) from UQ's Institute for Molecular Bioscience (https://imb.uq.edu.au/) with key contributions from Dr Ralph Patrick (https://imb.uq.edu.au/profile/16610/ralph-patrick) and Dr Marina Naval-Sanchez. (https://imb.uq.edu.au/profile/11267/marina-naval-sanchez) Dr Nefzger said that until now the process of how genes change activity from birth to adulthood and into old age was largely unknown. “By analysing molecular datasets from both people and mice and then comparing different age groups over time, we investigated the activity of genes involved in both developmental and ageing processes,” Dr Nefzger said. “Master controller genes regulate which genes are turned on or off in each of our cells, making sure that each cell does its specific job, just as a conductor directs musicians to produce different sounds. “We followed the activity of the master regulator Activator Protein 1 or AP-1 and found that it progressively activated adult genes, whilst the activity of ‘early- life’ genes involved in development were dialled down, and this process was shared across cell types.” Dr Naval-Sanchez said the study found this process in our cells was predictable across the different life stages, as people mature. “It was ongoing in adulthood, likely because AP-1 is also activated by a number of stress and inflammatory processes as well as by a protein in our blood that increases with age,” Dr Naval-Sanchez said. “This further dampens genes most active early in life, which may drive many of the predictable changes of ageing.” Dr Patrick said to address the diseases associated with ageing, like Alzheimer's disease, metabolic liver disorders and stroke, researchers must first understand the process causing bodies to age. “By pinpointing AP-1 as a master controller linked to ageing across cell types, we can now study the effects of drugs that reduce its activity to extend quality of life,” Dr Patrick said. Dr Nefzger said the goal is to prevent diseases of ageing from escalating or occurring in the first place by targeting the underlying ageing process to allow people to grow older in better health. The research was supported by the Australia’s National Health and Medical Research Council, along with funding from IMB. The project involved more than 15 Australian laboratories and international collaboration, including researchers from UQ, Monash University, CSIRO, Melbourne University, RMIT, St Vincent’s Institute of Medical Research and The Peter Doherty Institute. The research paper (https://doi.org/10.1016/j.cmet.2024.06.006) was published in Cell Metabolism.