title: Short Telomeres in Key Tissues Initiate Local and Systemic Aging in Zebrafish.
abstract: Telomeres shorten with each cell division and telomere dysfunction is a recognized hallmark of aging. Tissue proliferation is expected to dictate the rate at which telomeres shorten. We set out to test whether proliferative tissues age faster than non-proliferative due to telomere shortening during zebrafish aging. We performed a prospective study linking telomere length to tissue pathology and disease. Contrary to expectations, we show that telomeres shorten to critical lengths only in specific tissues and independently of their proliferation rate. Short telomeres accumulate in the gut but not in other highly proliferative tissues such as the blood and gonads. Notably, the muscle, a low proliferative tissue, accumulates short telomeres and DNA damage at the same rate as the gut. Together, our work shows that telomere shortening and DNA damage in key tissues triggers not only local dysfunction but also anticipates the onset of age-associated diseases in other tissues, including cancer.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Madalena C
authors.initials: MC
authors.lastname: Carneiro
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Henriques
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Nabais
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Ferreira
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Carvalho
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Miguel Godinho
authors.initials: MG
authors.lastname: Ferreira
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001773:Blood Cells; D002455:Cell Division / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D009928:Organ Specificity; D016615:Telomere / Q000235:genetics*; D059506:Telomere Shortening / Q000235:genetics*; D015027:Zebrafish