Telomere length measurements using flow FISH. (A) Nonlinear decline in telomere length with age. The average telomere length in granulocytes and lymphocytes from 392 healthy donors was calculated from the median telomere fluorescence and median autofluorescence relative to internal control cells (bovine thymocytes).⁶¹  Note that the telomere length at any given age is highly variable, that the most rapid drop in telomere length occurs early in life, and that the rate of telomere attrition in lymphocytes exceeds that in granulocytes. (B) Longitudinal studies of telomere length in newborn baboons point to a high turnover of hematopoietic stem cells in the first year of life.⁶²  Note that the 2 animals differ markedly in average telomere length and that the rate of telomere attrition drops markedly after approximately 1 to 2 years in both animals. In humans, with a longer lifespan, this drop is expected to occur before the fourth year of life in line with previous cross-sectional observations.⁶⁰  (C,D) Telomere length in individuals with mutations in telomere genes. The telomere length in cells from healthy individuals (A) was used to plot the telomere length distribution in the normal population using a best-fit approach (red, green, and blue curves representing expected telomere length for the indicated proportion of healthy individuals). The telomere length in lymphocytes (C) and granulocytes (D) from patients with known mutations in telomerase genes measured in the context of several studies^{12,–14,16,63}  are shown. Each symbol represents an individual patient diagnosed with clinical symptoms associated with a mutation in dyskerin (DKC1, black circles), hTERT (red circles), and hTERC (black squares). Some individuals are carriers of a TERC mutation but have no clinical symptoms (blue square). The majority of individuals that carry mutations in telomerase genes display critically short telomeres, nearly all of them below the tenth percentile of the normal distribution and a majority of these below the first percentile (typically for both cell subsets shown). Note that individuals with early onset of disease (in the first 3 decades of life) show the most striking difference between observed and expected telomere length.