A model of canine leukocyte telomere dynamics.

Recent studies have found associations of leukocyte telomere length (TL) with diseases of aging and with longevity. However, it is unknown whether birth leukocyte TL or its age-dependent attrition the two factors that determine leukocyte TL dynamics explains these associations because acquiring this information entails monitoring individuals over their entire life course. We tested in dogs a model of leukocyte TL dynamics, based on the following premises: (i) TL is synchronized among somatic tissues; (ii) TL in skeletal muscle, which is largely postmitotic, is a measure of TL in early development; and (iii) the difference between TL in leukocytes and muscle (?LMTL) is the extent of leukocyte TL shortening since early development. Using this model, we observed in 83 dogs (ages, 442 months) no significant change with age in TLs of skeletal muscle and a shorter TL in leukocytes than in skeletal muscle (P < 0.0001). Age explained 43% of the variation in ?LMTL (P < 0.00001), but only 6% of the variation in leukocyte TL (P = 0.035) among dogs. Accordingly, muscle TL and ?LMTL provide the two essential factors of leukocyte TL dynamics in the individual dog. When applied to humans, the partition of the contribution of leukocyte TL during early development vs. telomere shortening afterward might provide information about whether the individuals longevity is calibrated to either one or both factors that define leukocyte TL dynamics.