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Figure 8 | BMC Medical Genetics

Figure 8

From: Lack of increases in methylation at three CpG-rich genomic loci in non-mitotic adult tissues during aging

Figure 8

Types of observed human somatic cell genealogies. A: Static genealogy observed in adult non-mitotic tissues (heart, brain, kidney, liver). Genealogical phases are indicated by green (development from the zygote to the tissue stem cell), red (stem cell phase), and blue (differentiation). Adult genealogies and mitotic ages are fixed with respect to chronological age and replication errors in present day cells accumulated much earlier in life. B: Continuous genealogy observed in mitotic epithelium. Only the stem cell phase can vary with chronological age because numbers of divisions are relatively constant during development and differentiation. The mitotic age of a differentiated cell is the mitotic age of its stem cell plus the few additional divisions required for differentiation. An age-related increase in replication errors and mitotic age depends on stem cell divisions. C: Punctuated genealogy observed in hair follicles. Average mitotic age and replication errors do not increase with age despite the high hair follicle mitotic activity because hairs and their follicles are cyclically lost and destroyed every few years. Bulge stem cells initiate each new hair cycle, and the mitotic age of a differentiated follicle cell is the age of the stem cell that initiates the new cycle plus the divisions in the follicle. New hairs would have essentially the same mitotic age regardless of chronological age because bulge stem cells are relatively quiescent and only divide a few times at the start of each new hair cycle [26], or if there is clonal succession [25] in which new hair cycles are initiated by previously latent stem cells.

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