CpG Sites

Definition

CpG sites are locations in DNA where a cytosine nucleotide is followed by a guanine nucleotide, linked by the phosphate backbone of DNA. In mammals, cytosines at CpG sites are common targets for DNA methylation, an epigenetic modification that can help regulate gene activity, genome stability, and cell identity. [1] [2] [3]

Why It Matters in Ageing Research

CpG sites matter because many epigenetic clocks are built from methylation measurements at selected CpG locations across the genome. Some CpG sites gain or lose methylation with age, and statistical models can use these patterns to estimate chronological age, epigenetic age, mortality-related risk, or other ageing-related outcomes. However, a CpG site is only a genomic location; its biological meaning depends on where it sits and how methylation at that site relates to gene regulation and tissue context. [4] [5] [6]

Common Confusion

• CpG does not mean a C-G base pair; it means cytosine followed by guanine along the same DNA strand.
• CpG sites are not the same as DNA methylation; they are locations where methylation often occurs.
• Not every CpG site is part of an epigenetic clock or directly involved in ageing.

Related Reading

• DNA Methylation
• Epigenetic Age
• Epigenetic Clocks
• Epigenetics

References

1. Bird, A. (2002). DNA methylation patterns and epigenetic memory. https://doi.org/10.1101/gad.947102
2. Moore, L. D., Le, T., & Fan, G. (2013). DNA methylation and its basic function. https://doi.org/10.1038/npp.2012.112
3. Jones, P. A. (2012). Functions of DNA methylation: islands, start sites, gene bodies and beyond. https://doi.org/10.1038/nrg3230
4. Horvath, S. (2013). DNA methylation age of human tissues and cell types. https://doi.org/10.1186/gb-2013-14-10-r115
5. Horvath, S., & Raj, K. (2018). DNA methylation-based biomarkers and the epigenetic clock theory of ageing. https://doi.org/10.1038/s41576-018-0004-3
6. Levine, M. E., et al. (2018). An epigenetic biomarker of aging for lifespan and healthspan. https://doi.org/10.18632/aging.101414