Telomeres shorten at equivalent rates in somatic tissues of adults

Abstract

Telomere shortening in somatic tissues largely reflects stem cell replication. Previous human studies of telomere attrition were predominantly conducted on leukocytes. However, findings in leukocytes cannot be generalized to other tissues. Here we measure telomere length in leukocytes, skeletal muscle, skin and subcutaneous fat of 87 adults (aged 19-77 years). Telomeres are longest in muscle and shortest in leukocytes, yet are strongly correlated between tissues. Notably, the rates of telomere shortening are similar in the four tissues. We infer from these findings that differences in telomere length between proliferative (blood and skin) and minimally proliferative tissues (muscle and fat) are established during early life, and that in adulthood, stem cells of the four tissues replicate at a similar rate.

Figure 1. Correlation between TL and age in various tissues.

TL in leukocytes, muscle, skin and fat is plotted against age.

Figure 2. Differences in TL in tissues are stable.

Differences in TL (Δ) between tissues within the same individuals are plotted against the ages of the donors of the samples.

Figure 3. Equivalence in TL between tissues within the same individual.

Although the correlations between TLs of the four tissues are strong, the highly proliferative tissues (leukocytes and skin) consistently display shorter telomeres than the minimally proliferative tissues (muscle and fat).

Figure 4. Model of progenitor cell pool dynamics and in different tissues.

Upper panel: during growth (grey shade), the progenitor cell pool in the hematopoietic system undergoes massive expansion through asymmetric replication of hematopoietic stem cells. In this way, the system can accommodate the tremendous turnover in peripheral blood cells. In contrast, during growth, the progenitor cell pool in skeletal muscle undergoes a modest expansion through replication of muscle stem cells, as the turnover of skeletal muscle cells is small. Lower panel: reflecting the expansions of the progenitor cell pools in the respective systems, TL undergoes rapid attrition in the hematopoietic system but only modest attrition in skeletal muscle. The slow and parallel attritions of TLs in stem cells, as expressed in leukocyte TL and in skeletal muscle TL during adult life, are the outcome of ’maintenance’ replicative activities of stem cells/progenitor cells in these systems.