This week we profile a recent publication in Blood from Dr. Peter Lansdorp (pictured) at BC Cancer and UBC.
Can you briefly explain why telomeres are relevant in aging and disease?
The daily loss of cells in tissues such as skin, gut and blood is compensated by proliferation and differentiation of stem and progenitor cells. It has long been assumed that stem cells have “self-renewal” properties for this purpose, dividing hundreds if not thousands of times over a lifetime. However, we know that DNA repeats at the end of chromosomes are lost with each cell division and that progressive telomere loss can limit cell divisions, the so-called “Hayflick limit.” We know that telomeric DNA is lost in blood forming stem cells and in cells of the immune system and can compromise blood cell production and immune responses in the elderly. This is illustrated by the COVID pandemic. Telomeres also play an important role in cancer: the most common genetic alterations in cancer cells allow them to bypass the Hayflick limit.
What is the significance of the Telomere Erosion in Disposable Soma (TEDS) theory proposed in the article?
Damage to DNA is a major cause of aging in all multicellular organisms as the steady accumulation of mutations in DNA over time compromises the function of an increasing number of cells with age. In the paper I propose that, next to the accumulation of mutations, telomere erosion is a separate cause of aging in long-lived animals. Because telomere erosion does not appear to play a role in short-lived animals such as laboratory mice this cause of aging and mortality has been largely overlooked.
What are the next steps for research in this area?
Our current knowledge is largely based on a relatively low number of accurate measurements of the average length of telomere repeats in cells. However, we know that a few short telomeres in a cell can be sufficient to trigger cell senescence or apoptosis. So we need better tools to measure the length of individual telomeres next to the average telomere length in cells. By combining such measurements with measurements of accumulated mutations in different cells over time we should be able to get a much better picture of what drives aging in various organisms. Such knowledge will drive innovation and novel interventions to slow down the aging process.
