Harvard Research on mice providees long-awaited confirmation that DNA changes are not the only, or even the main, cause of aging. “We expect the findings to change our understanding of the ageing process and our approach to treating diseases associated with ageing,” said Jae-Hyun Yang, co-author of the first study, a genetics researcher in Sinclair’s laboratory.
For decades, a reigning theory in the field was that aging arises from an accumulation of changes to DNA, primarily genetic mutations, which over time prevent more and more genes from functioning properly. These malfunctions, in turn, cause cells to lose their identity, so that tissues and organs break down, leading to disease and, ultimately, death. In recent years, however, studies have increasingly hinted that there’s more to the story.
For instance, some researchers found that some people and mice with high mutation rates don’t show signs of premature aging. Others observed that many types of aged cells have few or no mutations.
At this stage, Sinclair says the discovery supports the hypothesis that mammalian cells maintain a kind of backup copy of epigenetic software that, when accessed, can allow an aged, epigenetically scrambled cell to reboot into a youthful, healthy state.
For now, the extensive experiments led the team to conclude that “by manipulating the epigenome, aging can be driven forwards and backwards,” said Yang. The ICE method offers researchers a new way to explore the role of epigenetics in aging and other biological processes.
Because signs of aging developed in the ICE mice after only six months rather than toward the end of the average mouse life span of two and a half years, the approach also saves time and money for researchers studying aging.
Researchers can also look beyond OSK gene therapy in exploring how lost epigenetic information might be restored in aged organisms. First, the results need to be replicated in larger mammals and in humans. Studies in nonhuman primates are currently underway. “We expect the findings will transform the way we view the process of aging and the way we approach the treatment of diseases associated with aging,” said co-first author Jae-Hyun Yang, research fellow in genetics in the Sinclair lab.
Sinclair hopes Harvard Research on mice inspires other scientists to study how to control aging to prevent and eliminate age-related diseases and conditions in humans, such as cardiovascular disease, type 2 diabetes, neurodegeneration, and frailty.
