Hyper-Long Telomeres Lead to Hyper-Long Life

The older an organism, the shorter its telomeres. Given this fact, CNIO scientists launched a study in mice in with hyper-long telomeres. The findings, published today in Nature Communications, show only positive consequences: The animals with hyper-long telomeres live longer in better health, free from cancer and obesity.

“This finding supports the idea that, when it comes to determining longevity, genes are not the only thing to consider,” indicates senior author Maria Blasco. “There is margin for extending life without altering the genes.”

Telomeres exist at the ends of chromosomes, and they function to protect DNA. Every time cells divide, the telomeres are shortened. But the researchers have already shown that preventing the shortening of telomeres extends organismal longevity without secondary effects. However, up until now, all interventions on the length of telomeres have been based on altering the expression of genes.

In 2009, the researchers were working with IPS cells and observed that after a certain number of divisions in culture plates, these cells acquired telomeres that were twice as long as normal. Intrigued, they confirmed that the same occurred in normal embryonic cells. The team then found that during the pluripotency stage, there are certain biochemical marks (epigenetic marks) on the telomeric chromatin that facilitate their lengthening by the telomerase enzyme.

The question was whether the embryonic cells with hyper-long telomeres could produce live mice. Some years ago, the group demonstrated that they could; however, these first animals were chimerical. Only between 30% and 70% of their cells had the hyper-long telomeres. But in the new study, the authors have managed to obtain hyper-long telomeres in 100% of mouse cells.

“These mice have less cancer and live longer,” the authors say. “An important fact is that they are slimmer than normal because they accumulate less fat. They also show lower metabolic aging, with lower levels of cholesterol and LDL (bad cholesterol), and an increased tolerance to insulin and glucose. Damage to their DNA as they age is less, and their mitochondria, another Achilles heel of aging, function better.”

The average longevity of mice with hyper-long telomeres is 13% higher than usual.

Image: Images of fat, liver, and skin of adult mice with normal or hyper-long telomeres. In blue, nuclei; in red, telomeres. Telomeres of adult cells that are derived from the animals with the so-called hyper-long telomeres are brighter, indicating longer telomeres through adult life. Image courtesy of CNIO.