The house mouse maintains constant telomere length throughout life

Abstract

Telomeres protect the chromosome ends from deleterious DNA damage response and repair activities. In humans, telomerase maintains telomere length in germ and stem cells, but not in most somatic cells. Consequently, telomeres shorten with cell division and age, limiting cell proliferation and protecting against cancer. When telomeres become critically short, they may also cause senescence, inflammation, and organ failure, which are major drivers of aging. Therefore, maintaining an optimal, age-appropriate telomere length is crucial for healthy aging. In the house mouse, Mus musculus, telomerase is active in most somatic tissues, yet its long telomeres were thought to shorten rapidly with age. We have followed telomere length over age in blood and tail of wild-type M. musculus and in two engineered mouse strains with shorter telomeres (Telomouse and HHS mouse). We also measured the precise length of single telomeres in blood leukocytes of these mouse strains by a long-read nanopore sequencing method, NanoTelSeq. We show that telomeres in blood and tail of these three mouse strains do not shorten with age. We conclude that M. musculus maintains long telomeres in blood and tail throughout life, excluding the possibility that global telomere shortening in these tissues contribute to aging-associated phenotypes.