Previous studies show that animal models have been the go-to technique to study the biological consequences of aging, especially in tissues that can’t be easily sampled from living humans, like the brain. Over the past few years, researchers have increasingly turned to stem cells to study various diseases in humans. Patients’ skin cells have been turned into induced pluripotent stem cells, which have the ability to become any cell in the body. From there, researchers can prompt the stem cells to turn into brain cells for further study. However, this process, even when taking skin cells from an older human, doesn’t guarantee stem cells with ‘older’ properties. Epigenetic signatures in older cells, patterns of chemical marks on DNA that dictate what genes are expressed when, were reset to match younger signatures in the process. This made studying the aging of the human brain difficult, since researchers couldn’t create ‘old’ brain cells with the approach. The current study directly converted skin cells to neurons, creating what’s called an induced neuron (iNs) to display age-specific transcriptional profiles and age-associated changes.
The current study used skin cells from 19 people, aged from birth to 89, and prompted them to turn into brain cells using both the induced pluripotent stem cell technique and the new direct conversion approach. The lab then compared the patterns of gene expression in the resulting neurons with cells taken from autopsied brains.
Data findings show that when the induced pluripotent stem cell method was used, as expected, the patterns in the neurons were indistinguishable between young and old derived samples. In contrast, results show brain cells that had been created using the direct conversion technique had different patterns of gene expression depending on whether they were created from young donors or older adults. The group observed that the direct conversion technique neurons showed differences depending on donor age and actually show changes in gene expression that have been previously implicated in brain aging. The researchers explain, as an example, levels of a nuclear pore protein called RanBP17 whose decline is linked to nuclear transport defects in neurodegenerative diseases, were lower in the neurons derived from older patients.
The team surmise that by using this powerful approach, the global medical community can begin to answer many questions about the physiology and molecular machinery of human nerve cells, not just around healthy aging but pathological aging as well. For the future, the researchers state now that the direct conversion of skin cells to neurons has been shown to retain these signatures of age they expect the technique to become a valuable tool for studying aging.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
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Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.