Why Is The Human Brain So Prone to Age-Related Diseases?
Impaired energy production in older neurons may help explain why human brains are so vulnerable to age-related diseases, according to a new study at Salk Institute in California.
The scientists used a new strategy to discover that cells from older people had dysfunctional mitochondria — the power stations of cells — and lower energy production.
Mitochondria are responsible for converting our food into chemical energy our cells can use. Defects in mitochondrial genes can lead to disease, but researchers also know that mitochondria become less efficient with age and can drive age-related disorders, such as Alzheimer’s and Parkinson’s.
Studying the impact of aging on mitochondria could help researchers gain a better understanding of the known link between mitochondrial dysfunction and age-related brain diseases.
The new findings are published in the journal Cell Reports.
“Most other methods use chemical stresses on cells to simulate aging,” said senior author Dr. Rusty Gage, a professor in Salk’s Laboratory of Genetics. “Our system has the advantage of showing what happens to mitochondria that age naturally, within the human body.”
Previously, Gage’s research team had developed a method to directly convert skin cells into neurons (called induced neurons, or iNs). Most techniques to create neurons from patient cells depend on an intermediary stem cell step (creating what are called induced pluripotent stem cells), which resets cellular markers of aging. But these iNs retained signs of aging, including changes to gene activity and the cells’ nuclei, the team reported in 2015.
In the current study, the scientists wanted to investigate whether mitochondria in the cells also retained hallmarks of aging during the iN conversion process. So, using skin cells taken from humans ranging in age from 0 to 89 years old, the researchers created iNs from each donor and then used a variety of methods to study the mitochondria of each set of cells.
Mitochondria in the skin cells isolated from each person exhibited few age-related changes. However, when the cells were directly converted to neurons, mitochondria from older donors were significantly different. For example, the mitochondrial genes associated with energy production were turned off and the mitochondria were less dense, more fragmented and generated less energy.
“Pretty much every area we looked at — functional, genetic, and morphological — had defects,” said Dr. Jerome Mertens, a Salk staff scientist and co-corresponding author of the new paper.
The scientists hypothesized that the reason the mitochondria of iNs were more affected by aging than the mitochondria of skin cells was that neurons depend more heavily on mitochondria for energy.
“If you have an old car with a bad engine that sits in your garage every day, it doesn’t matter,” Mertens said. “But if you’re commuting with that car, the engine becomes a big problem.”
The finding shows how aging can impact organs differently throughout the body.
Next, the team plans to apply their technique to study age-related diseases, including Alzheimer’s and Parkinson’s. In previous work, mitochondrial defects have been implicated in these diseases. By collecting skin cells from patients with these diseases and creating iNs, the team can look at how neuronal mitochondria from these patients are different from neuronal mitochondria in unaffected older individuals.
“There is no other in vitro human neuronal model to study aging,” said Dr. Yongsung Kim, a research associate and first author of the paper. “So the big takeaway from our paper is that we developed a tool that enables us to study neurological aging and age-related diseases.”
Source: Salk Institute
Pedersen, T. (2018). Why Is The Human Brain So Prone to Age-Related Diseases?. Psych Central. Retrieved on September 19, 2020, from https://psychcentral.com/news/2018/05/30/why-is-the-human-brain-so-prone-to-age-related-diseases/135770.html