Unravelling the ageing puzzle
Increased longevity has raised concerns about promoting healthy ageing to mitigate the socioeconomic burden of age-related disorders such as diabetes arising from an unhealthy lifestyle. Though hormonal and gene expression changes are linked to ageing, the underlying mechanisms are still poorly understood. To understand the molecular or physiological changes that drive ageing, the project INTEGRAGEING (Modelling human ageing: Developing and interrogating an integrated model of ageing to identify causal relationships between hormonal changes and gene expression changes) was initiated. Researchers analysed gene expression and physiological changes that occur during ageing and employed mathematical models as well as computational methods. INTEGRAGEING reviewed and collected age-related changes from scientific literature and categorised them in the Digital Ageing Atlas database. This database includes data on ageing-related hormonal and molecular changes. Currently, this database contains over 2 600 gene expression changes and information on hormones such as insulin-like growth factor (IGF), growth hormone and adrenocorticotropic hormone. Scientists converted this data into linear and non-linear mathematical models to understand ageing-related changes in hormonally activated signalling pathways and alterations in gene expression. They focused on major hormones linked to ageing such as insulin and IGF1 as well as longevity-associated genes. Using flies as a model organism, researchers studied ageing-related tissue-specific gene expression changes occurring from dietary manipulations. They also investigated the role of neuropeptides and hormonal signalling in inter-tissue communication. INTEGRAGEING has developed a computational pipeline and methodology that could also be used to study other genes and biological processes. Project activities and tools should provide deeper insight into the physiological and molecular mechanisms involved in healthy ageing as well as age-related disorders.
Keywords
Ageing, longevity, gene expression, physiological changes, hormonal changes
