Mice with hyper-long telomeres show less metabolic aging and longer lifespans

• Published in: Nature communications Vol. 10; no. 1; pp. 4723 - 14
• Main Authors: Muñoz-Lorente, Miguel A., Cano-Martin, Alba C., Blasco, Maria A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.10.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/1; 14/19; 14/32; 38/32; 38/77; 38/88; 38/90; 631/45; 631/532; 631/61; 631/67; 631/80; 64/60; Aging; Aging - genetics; Aging - metabolism; Animals; Cholesterol; Deoxyribonucleic acid; DNA; DNA Damage; Embryonic Stem Cells - metabolism; Glucose tolerance; Humanities and Social Sciences; Humans; Insulin; Life span; Longevity - genetics; Low density lipoprotein; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Neoplasms - genetics; Science; Science (multidisciplinary); Telomerase; Telomere - genetics; Telomere Homeostasis - genetics; Telomeres; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12664-x

Short telomeres trigger age-related pathologies and shorter lifespans in mice and humans. In the past, we generated mouse embryonic (ES) cells with longer telomeres than normal (hyper-long telomeres) in the absence of genetic manipulations, which contributed to all mouse tissues. To address whether hyper-long telomeres have deleterious effects, we generated mice in which 100% of their cells are derived from hyper-long telomere ES cells. We observe that these mice have longer telomeres and less DNA damage with aging. Hyper-long telomere mice are lean and show low cholesterol and LDL levels, as well as improved glucose and insulin tolerance. Hyper-long telomere mice also have less incidence of cancer and an increased longevity. These findings demonstrate that longer telomeres than normal in a given species are not deleterious but instead, show beneficial effects. Telomere shortening is associated with aging. Here the authors analyze mice with hyperlong telomeres and demonstrate that longer telomeres than normal have beneficial effects such as delayed metabolic aging, increased longevity and less incidence of cancer.