Scientists from the Chinese Academy of Sciences and Monash University report that they have developed a new method to measure biological aging in individual cell types. The new tool offers a more detailed understanding of how cells age, providing insights into diseases such as Alzheimer’s and liver pathologies, leading the way for more precise health assessments and targeted therapies, according to the researchers who published their study “Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution” in Aging.
Biological age refers to how old a person’s body is biologically, which may differ from their actual age in years. Typically, biological age is estimated using “epigenetic clocks,” which rely on DNA methylation patterns linked to aging. Standard methods analyze all the cells from a specific tissue at once, making it difficult to understand the aging processes in the different cell types that constitute the tissue.
To address this, the team analyzed DNA samples from human brain and liver tissues to create a new analysis tool. With the help of advanced computer models, they studied changes in DNA methylation in samples from healthy and diseased individuals. By isolating biological aging within specific cell types, the team could better understand how these changes contribute to diseases like Alzheimer’s or liver conditions.
Accurately quantifying biological age
“The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating biological age, yet they have been developed from heterogeneous bulk tissues, and are thus composites of two aging processes, one reflecting the change of cell-type composition with age and another reflecting the aging of individual cell-types. There is thus a need to dissect and quantify these two components of epigenetic clocks, and to develop epigenetic clocks that can yield biological age estimates at cell-type resolution,” write the investigators.
“Here we demonstrate that in blood and brain, approximately 39% and 12% of an epigenetic clock’s accuracy is driven by underlying shifts in lymphocyte and neuronal subsets, respectively. Using brain and liver tissue as prototypes, we build and validate neuron and hepatocyte specific DNA methylation clocks and demonstrate that these cell-type specific clocks yield improved estimates of chronological age in the corresponding cell and tissue-types.
“We find that neuron and glia specific clocks display biological age acceleration in Alzheimer’s Disease with the effect being strongest for glia in the temporal lobe. Moreover, CpGs from these clocks display a small but significant overlap with the causal DamAge-clock, mapping to key genes implicated in neurodegeneration. The hepatocyte clock is found accelerated in liver under various pathological conditions. In contrast, non-cell-type specific clocks do not display biological age-acceleration, or only do so marginally.
The study revealed that certain brain cells, like neurons and glia, age faster in people with Alzheimer’s disease, suggesting that the aging of specific cell types plays a critical role in neurodegeneration. In liver diseases, such as fatty liver disease and obesity, the clock for liver cells showed signs of accelerated aging, making it a better tool than previous methods for detecting liver problems.
Their research highlights the critical importance of precision in aging research, allowing deeper insights into the aging process and significant advancements in the prevention, diagnosis, and treatment of age-related diseases, points out the scientific team.
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