Posted on 16 December 2016
In potentially one of the biggest findings of the year, researchers have found that brief, cyclical treatment of mice with a cocktail of proteins used to create stem cells extends life and causes significant rejuvenation
In 2006 Shinya Yamanaka and his team released a paper detailing a technique able to create induced pluripotent stem cells from adult mouse fibroblast cells. These factors, Oct3/4, Sox2, Klf4, c-Myc (OSKM) are present in embryonic stem cells, and applying them to adult cells is able to trigger a similar transformation process – turning them into a type of cell with very similar abilities and qualities as embryonic stem cells do: induced pluripotent stem cells (IPSCs). Further analysis of these factors revealed that they are able to reverse some of the marks of the aging process, partially by removing many of the epigenetic marks that change with age. The degree they are able to do this is debatable and appears to vary, but the process seems to trigger some form of clock reset, regardless of how potent the reset is. A word of caution however; over exposure to these factors can causes cancerous tumours. After all, embryos are required to go through rapid growth. A startling discovery Keen to replicate these rejuvenative effects on a live organism, researchers decided to test a smaller dosage in a mouse model of the accelerated aging disorder progeria. Progeria patients display many early onset signs of aging, one of them being early epigenetic changes.“Our study shows that aging may not have to proceed in one single direction. It has plasticity and, with careful modulation, aging might be reversed”
Partial cellular reprogramming reverses cellular signs of aging such as accumulation of DNA damage. (Left) Progeria mouse fibroblast cells; (right) progeria mouse fibroblast cells rejuvenated by partial reprogramming. Credit: Salk Institute
“This work shows that epigenetic changes are at least partially driving aging. It gives us exciting insights into which pathways could be targeted to delay cellular aging. Obviously, mice are not humans and we know it will be much more complex to rejuvenate a person. But this study shows that aging is a very dynamic and plastic process, and therefore will be more amenable to therapeutic interventions than what we previously thought“
When they tested the OSKM factors with a molecule that inhibits epigenetic alterations, they found many of the benefits melted away. This provides strong evidence that maladaptive epigenetic regulation plays an important role in the aging process. Read more at MedicalXpressCopyright © Gowing Life Limited, 2023 • All rights reserved • Registered in England & Wales No. 11774353 • Registered office: Ivy Business Centre, Crown Street, Manchester, M35 9BG.