When we think about aging, we generally think about it as a whole-body process; wrinkles form, hearing gets harder, muscles get weaker—everything happens at once. But a new study out of the Salk Institute has revealed that age affects organs differently at the molecular level.
“Our study showed that organs have different aging mechanisms and that aging is largely driven by changes in protein production and turnover,” explained Martin Hetzer, Salk professor and co-senior author of the paper published in Cell Systems.
Two kinds of “omics”
Aging leads to progressive degeneration of the functions of organs, cells, and proteins, but it wasn’t entirely clear how aging affect proteins, or whether these effects vary across different organs.
So to study this, the team took a unique approach that combined genomics and proteomics—the studies of the structure and function of DNA and proteins, respectively.
They analyzed various changes in protein creation, modification, and levels in the brains and livers of young and old rats, and found multiple differences between the two age groups. For example, there were 468 differences in the amounts of different types of proteins.
In another 130 proteins, age affected where they were located within a cell, or how they were modified (via phosphorylation and splicing, in these cases)—changes which affect the activity level and function of those proteins.
“Our work significantly expands the list of proteins that are affected by chronological age in mammals,” said senior author Martin Beck of the European Molecular Biology Laboratory. “In most cases, individual datasets would not have been sufficient to extrapolate these networks, highlighting the complexity of the effects of chronological age on the proteome and the benefits of our integrative approach.”
However, the even bigger discovery was that protein aging was much more prevalent in the brains than in the livers. Protein aging tends to correspond with an organ’s properties, like how often cells get replaced.
Liver cells have frequent turnover rates, meaning the organ can replenish its proteins frequently. Brains, however, are much more static—most neurons must survive for the lifetime of an organism. The proteins within brains don’t get replaced as often or as easily, and so are much more vulnerable to the accumulation of damage or to loss of function as the brain ages.
This means that a larger fraction of brain proteins are affected by aging, as compared to liver proteins. In particular, the rats showed changes in proteins necessary for neuronal plasticity (roughly, the ability for cells to adapt) and memory formation.
There were important changes in the liver as well, though—proteins involved in metabolic networks were changed.
“Based on our findings, we would define aging as an organ-specific deterioration of the cellular proteome,” said Hetzer. In other words: Aging changes the numbers and functions of different types of proteins in your organs, making them less able to perform all their duties.
This is an important understanding, because it could mean new treatments for various diseases.
“This research may shed new light on the molecular mechanisms underlying age-related diseases, enabling the identification of risk factors to predict which individuals are most susceptible based on their genetic makeup,” Beck said. “In the end, a better understanding of the molecular mechanisms of aging could lead to the development of novel therapies to prevent or treat a range of age-related diseases.”
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Feature Image: Hey Paul Studios/Flickr
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