Researchers from the Hebrew University of Jerusalem have found that cells that age slowly and cells in which epigenetic changes accumulate rapidly coexist within the same tissue. The study, published in Nature Communications, was conducted at the single-cell level.
Cells Living side by side in the same tissue and formed at the same time do not necessarily age at the same rate. A new study by The Hebrew University shows that over the course of life, tissues become a kind of mosaic: most cells slowly accumulate age-related changes, while a smaller group moves on a trajectory of aging Accelerated epigenetics.
The study, published in the journal Nature Communications., conducted under the leadership of Dr. Hagit Mesika, supervised by Prof. Chaim (Howard) Cedar and Prof. Tommy Kaplan from the Faculty of Medicine and the Center for Computational Medicine at the Hebrew University. Prof. Wolf Reich from Altos Labs and the Brahm Institute in Cambridge, and researchers from other institutions also participated in the study.
Moving from the average of the tissue to the single cell
Much of traditional biological research relies on the collective measurement of millions of cells. This method provides an average value for the tissue, but can hide processes that occur in only a small number of cells.
The researchers analyzed data on DNA methylation At the single-cell level, collected from various tissues of humans and mice of different ages. Methylation is the addition of chemical groups to certain locations along DNA. It does not change the genetic sequence itself, but may affect the activity of genes.
Methylation patterns change throughout life, so they are used in many studies to measure Biological ageIn the current study, the team focused on CpG regions associated with the Polycomb system – a mechanism that helps a cell silence groups of genes and maintain its identity.
The analysis revealed that the increase in methylation in these regions did not occur uniformly. Cells from the same tissue and chronological age sometimes displayed markedly different patterns. The variation between cells increased with age, and in some tissues, a small group of cells emerged in which signs of aging accumulated at a particularly rapid rate.
According to Dr. Messika, the ability to measure the process in each cell individually revealed variability that was hidden in the average measurements: “Two cells located side by side can have completely different biological ages.”
Rapidly dividing cells aged faster
One of the key findings was the relationship between the rate of cell division and the accumulation of methylation. Cells that divided more frequently tended to accumulate age-related epigenetic changes more rapidly.
The researchers also found that in cells with advanced epigenetic age, the activity of genes related to the immune system, protein production, tumor development, and neurodegenerative processes was altered. The finding does not prove that these cells cause disease, but it does indicate a possible link between accelerated aging of individual cells and the early stages of pathological processes.
This distinction is important because many diseases begin with a change that occurs in a single cell or a small group of cells. Measuring whole tissue can miss such a small population until it grows or affects its environment.
Prof. Kaplan explained that analyzing the cells individually made it possible to identify patterns that were not seen when the results from the entire tissue were calculated together. He said that the approach may help in the future to identify cells that are at higher risk of participating in the development of disease.
White and black hairs from the same person
The researchers also examined white and black hairs taken from the same person. The white hairs consistently showed a more aged methylation pattern than the black hairs. This was a clear demonstration that cells and tissue parts in the same body may progress through different aging pathways.
However, the researchers emphasize that the phenomenon is not necessarily the same in all organs of the body. In the tissues examined in the study, the variation between cells increased with age, but previous studies have found other tissues that age more uniformly. It is therefore possible that different organs have different aging trajectories.
Also, the epigenetic aging measured in the study is not necessarily the same asCellular aging A type of senescence, in which a cell stops dividing but remains active. The current study tracked methylation patterns used as markers of biological age, and did not determine that every cell with an aged epigenetic signature is a cell that has stopped dividing.
Still no way to slow down aging
The findings may help develop more accurate methods for monitoring aging and early identification of abnormal cell populations. However, this is a basic research stage: the study does not offer a treatment to slow aging and does not prove that interfering with methylation patterns will prevent cancer or degenerative diseases.
The next step will be to examine what factors cause a particular cell to switch to the accelerated pathway, whether the process is reversible, and what the causal relationship is with age-related diseases. The key finding for now is that biological age is not a characteristic of just one person, organ, or tissue. It may differ from cell to cell.
Questions and Answers
How can the biological age of a cell be measured? Among other things, by examining DNA methylation patterns, which typically change throughout life.
Are cells from the same tissue the same biological age? Not necessarily. The study found significant differences between neighboring cells of the same chronological age.
Which cells tended to age faster? Cells that divided at a faster rate tended to quickly accumulate methylation marks associated with aging.
Does the research offer an anti-aging treatment? No. This is basic research describing the process at the single cell level. Further studies will be required before therapeutic conclusions can be drawn from it.
More on the subject on the science website
- DNA Methylation Atlas: The Secret Map of Inheritance
- Inventory count of senescent cells
- to open blockages in the immune system
- Aging cells, young heart
- Get rid of old hair
For the scientific article: Opening the scientific article