Ageing is a universal process that affects every living organism. While we cannot stop ageing, scientists have been tirelessly working to slow it down. The goal is to find compounds that not only extend lifespan but also enhance the quality of life during those years. This quest has led to numerous studies and experiments, but the journey has been fraught with challenges. Traditional methods for discovering anti-ageing drugs are time-consuming and complex, often requiring years of research and validation. However, a new tool, the CellPopAge Clock, promises to revolutionise this process, making the discovery of anti-ageing compounds faster and more efficient.
Challenge of anti-ageing drug Discovery
The primary challenge in anti-ageing drug discovery lies in the complexity of the ageing process itself. Ageing involves various biological mechanisms, including cellular senescence, DNA damage, and epigenetic changes. To identify compounds that can effectively slow down these processes, researchers need reliable and efficient screening methods.
Current techniques often involve lengthy longevity studies in model organisms, which can take years to yield results. Additionally, translating these findings from model organisms to humans presents another layer of difficulty.
There is a clear need for a method that can quickly and accurately screen potential anti-ageing compounds in a human-relevant system.
Introducing the CellPopAge clock
The CellPopAge Clock is a groundbreaking tool developed by a team of researchers led by Celia Lujan, Eleanor Jane Tyler, and Simone Ecker. This innovative screening platform leverages the concept of DNA methylation to monitor cellular aging. DNA methylation is an epigenetic modification that plays a crucial role in regulating gene expression.
As cells age, their DNA methylation patterns change in a predictable manner. By measuring these changes, the CellPopAge Clock can determine the age of a cell population with high accuracy.
What sets the CellPopAge Clock apart from other epigenetic clocks is its specific design for detecting anti-ageing compounds in vitro, making it a unique and valuable tool in the field of gerontology.
How the CellPopAge clock works
The CellPopAge Clock operates by analysing DNA methylation patterns at specific CpG sites across the genome. CpG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide.
These sites are prone to methylation, and changes in their methylation status can serve as indicators of cellular age. The researchers used Illumina methylation arrays to monitor DNA methylation changes during long-term culturing of adult primary human cells.
By doing so, they developed and validated the CellPopAge Clock, which uses an algorithm to predict the age of a cell population based on its DNA methylation profile. This allows for the rapid screening of compounds to see if they can decelerate the ageing process at the cellular level.
Validation of the CellPopAge clock
Validation is a crucial step in establishing the reliability of any scientific tool. The researchers rigorously tested the CellPopAge Clock against other existing epigenetic clocks, such as the Multi-Tissue Clock, the Skin and Blood Clock, and the PhenoAge Clock.
These clocks have been used to estimate biological age based on DNA methylation levels. However, the CellPopAge Clock outperformed them in accurately detecting age-related changes in primary human cells.
This superior performance underscores the Clock's precision and reliability. By accurately predicting cellular age, the CellPopAge Clock provides a robust tool for screening potential anti-ageing compounds.
Discovering New Anti-Ageing Compounds
The primary purpose of the CellPopAge Clock is to identify new anti-ageing compounds quickly and efficiently. Using this tool, the researchers screened various compounds and identified two promising candidates: torin2 and dactolisib (BEZ-235).
These compounds were shown to decelerate the epigenetic ageing of cells in vitro. Torin2 is a selective inhibitor of the mTOR pathway, which is known to play a significant role in regulating lifespan and healthspan.
Dactolisib, on the other hand, is a dual inhibitor of the PI3K and mTOR pathways. Both compounds demonstrated significant potential in slowing down the cellular ageing process, marking a significant breakthrough in anti-ageing research.
In vivo testing with drosophila
To confirm the efficacy of these compounds, the researchers conducted in vivo tests using the fruit fly, Drosophila melanogaster. Drosophila is an ideal model organism for ageing studies due to its short lifespan and well-characterised ageing markers.
The researchers reared the flies on a specially formulated holidic medium to increase drug bioavailability. They tested the compounds at various concentrations and observed significant lifespan extension in the flies treated with torin2 and dactolisib.
The results showed that these compounds not only slowed down the ageing process at the cellular level but also had a positive impact on organismal lifespan. This reinforces the potential of torin2 and dactolisib as effective anti-ageing drugs.
Broader implications of the CellPopAge clock
The development of the CellPopAge Clock represents a significant advancement in the field of anti-ageing research. By providing a rapid and accurate method for screening potential anti-ageing compounds, the Clock accelerates the discovery process and reduces the time required to identify effective treatments.
This tool can also be used to study the mechanisms of ageing at a cellular level, providing valuable insights into the biological processes that drive ageing.
Furthermore, the CellPopAge Clock has the potential to be adapted for use with different cell types and organisms, broadening its applicability in gerontological research.
Future directions and potential of CellPopAge Clock
The successful development and validation of the CellPopAge Clock open up numerous possibilities for future research. Researchers can use this tool to explore new anti-ageing pathways and identify novel compounds that can extend lifespan and healthspan.
Additionally, the CellPopAge Clock can be used in conjunction with other ageing biomarkers to provide a comprehensive assessment of a compound's anti-ageing potential. This multi-faceted approach can help to uncover new therapeutic targets and develop more effective treatments for age-related diseases.
In the long term, the CellPopAge Clock could also play a role in personalised medicine. By analysing an individual's cellular age, doctors could tailor anti-ageing treatments to their specific needs, potentially delaying the onset of age-related conditions and improving overall health outcomes.
As our understanding of the ageing process continues to evolve, tools like the CellPopAge Clock will be instrumental in translating this knowledge into practical interventions that enhance human health and longevity.
The study is published in the journal Genome Medicine. The research was led by Ivana Bjedov from UCL Cancer Institute.
