Aging may be far less synchronized than scientists have traditionally assumed. A new study published in Nature Communications reports that cells of the same chronological age can follow dramatically different biological aging trajectories, even when they are located beside one another in the same tissue. Most cells appear to remain relatively young for much of their lifespan, while a smaller population enters an accelerated aging state and accumulates molecular changes associated with aging much faster. The findings suggest that tissues gradually become biological mosaics, containing cells that are effectively younger or older than their surroundings.
The research, led by Dr. Hagit Masika under the supervision of Professors Howard Cedar and Tommy Kaplan at the Hebrew University of Jerusalem, was conducted in collaboration with Professor Wolf Reik of Altos Labs and the Babraham Institute in Cambridge. The investigators examined individual cells from multiple mouse and human tissues instead of relying primarily on measurements from entire tissue samples. This distinction was crucial because conventional tissue-level analysis averages molecular signals across millions of cells, potentially concealing small groups that are aging unusually quickly.
The team focused on DNA methylation, an epigenetic process that helps regulate gene activity. In this process, chemical groups called methyl groups are added to DNA, often at sites where cytosine is followed by guanine, known as CpG sites. Patterns of methylation change throughout life and can serve as biological clocks, providing an estimate of a cell’s biological age that may differ from its chronological age. The researchers paid particular attention to the gain of methylation at polycomb CpG islands, genomic regions associated with developmental regulation and the activity of Polycomb group proteins.
When methylation data were analyzed at single-cell resolution, aging-related variation became clearly visible. Cells from the same tissue and organism did not progress through epigenetic aging at a uniform rate. Instead, the researchers observed a broad distribution of biological ages, with most cells following a relatively gradual trajectory and a smaller subset showing markedly advanced methylation patterns. This accelerated group appeared to contribute disproportionately to the increasing variation between cells observed in older tissues.
The study also identified a connection between cellular proliferation and accelerated epigenetic aging. Rapidly dividing cells were more likely to display the molecular signature associated with faster aging. Each round of cell division requires the genome to be copied and its regulatory landscape to be restored, creating opportunities for errors or incomplete maintenance of epigenetic information. Repeated proliferation may therefore increase the likelihood that a cell will accumulate abnormal methylation, particularly at regulatory regions that are normally protected from inappropriate silencing.
The biological consequences of this process may extend beyond the methylation clock itself. Cells with advanced epigenetic ages showed altered activity in genes involved in immune responses, protein production, neurodegeneration, and tumor development. These changes do not prove that accelerated methylation directly causes disease, but they indicate that cells with older molecular profiles may also be functionally distinct. A small population of unusually aged cells could therefore influence tissue behavior, weaken local repair mechanisms, or create conditions that allow abnormal cells to survive and expand.
One of the study’s most visually striking observations came from hair. The investigators compared black and white hairs collected from the same individual and found that white hairs consistently carried an older epigenetic signature. Because neighboring hair follicles can experience similar systemic conditions while producing different pigmentation outcomes, the result provides an accessible example of how biological aging can diverge at the level of individual structures. It also supports the idea that visible age-related traits may reflect local cellular histories rather than a single aging rate imposed uniformly across the entire body.
The researchers emphasize that increasing cellular heterogeneity is not universal across all tissues. Some organs and cell populations may age in a comparatively uniform manner, while others become increasingly diverse with age. Differences in cell turnover, exposure to inflammation, metabolic demands, stem-cell activity, and tissue architecture could determine which aging pattern emerges. The findings therefore challenge the idea of a single biological clock governing the whole organism and instead point toward multiple, tissue-specific aging processes that operate simultaneously.
By identifying individual cells that appear to enter an accelerated aging state, the study could influence how scientists investigate cancer, neurodegeneration, and other age-related disorders. Future research may determine whether these cells are causes, consequences, or both of tissue decline, and whether their molecular state can be slowed or reversed. Single-cell epigenetic profiling could eventually help reveal the earliest cellular changes preceding disease, allowing researchers to distinguish vulnerable cells from those that remain resilient. For now, the central message is clear: aging is not a synchronized march shared equally by every cell, but a gradual divergence in which some cells move into biological old age long before their neighbors.
Subject of Research: Cells
Article Title: Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging
News Publication Date: 9-Jun-2026
Web References: https://doi.org/10.1038/s41467-026-74118-5
References: Nature Communications, DOI: 10.1038/s41467-026-74118-5
Keywords: Aging, biological age, epigenetics, DNA methylation, single-cell analysis, polycomb CpG islands, cellular heterogeneity, cancer, neurodegeneration, genomics
