In most labs, telomeres and mitochondria are studied as separate drivers of aging. But at Salk, Professors Jan Karlseder and Gerald Shadel have teamed up to explore crosstalk between the two.
Karlseder is an expert in telomeres, the protective DNA caps at the end of chromosomes. While short telomeres are associated with aging, Karlseder found that forcing cells to generate overly long telomeres can also be harmful, leading to stress and potentially cancer. Lengthening telomeres to reverse aging is not as simple as it might seem, his team concluded.
Shadel is an expert in mitochondria, the organelles that generate energy for cells. He’s especially interested in reactive oxygen species, toxic by-products of the process by which mitochondria generate energy. These molecules are normally thought of as detrimental to cells, but his lab is ﬁnding they actually have a second function—triggering beneﬁcial adaptive responses.
Now working together, Karlseder and Shadel have discovered that shortening telomeres kick off a cascade of molecular signals that reach the cell’s mitochondria. These signals ultimately trigger inﬂammation and cell death. This way, aging and unstable cells with critically short telomeres are efficiently removed by the body, preventing them from becoming cancerous. Stabilizing this pathway could offer a new approach for preventing age- related cancers.