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A study by nan Leibniz Institute connected Aging - Fritz Lipmann Institute (FLI) successful Jena shows that nan chemic creation of proteins successful nan encephalon undergoes basal changes pinch aging. In particular, ubiquitylation - a process that marks proteins and frankincense controls their activity and degradation - undergoes drastic changes successful nan aging brain. Interestingly, a alteration successful nutrition, specified arsenic short-term dietary restriction, tin partially revert immoderate of these molecular patterns. These findings unfastened up caller opportunities to amended understand nan aging process of nan encephalon and related diseases.
As we age, nan creation and usability of proteins successful nan encephalon change, affecting really good our encephalon performs later successful life - influencing memory, responsiveness, and nan consequence of neurodegenerative diseases. An world investigation squad led by Dr. Alessandro Ori from nan Leibniz Institute connected Aging - Fritz Lipmann Institute (FLI) successful Jena has now discovered that a circumstantial chemic modification, known arsenic ubiquitylation, plays a important domiciled successful these processes. This modification determines which proteins stay progressive and which are targeted for degradation. The findings person been published successful Nature Communications.
How aging alters encephalon proteins
Proteins execute captious tasks successful nan encephalon - they power metabolism, awesome transmission, and power equilibrium successful cells. To usability properly, they must beryllium perpetually surgery down, renewed, aliases chemically modified. One of these modifications, nan alleged ubiquitylation, serves arsenic a benignant of molecular tag: it marks proteins for degradation and regulates their activity.
Our analyses person shown that aging leads to basal changes successful really nan proteins successful nan encephalon are chemically labelled. The ubiquitylation process acts for illustration a molecular move - it determines whether a macromolecule remains active, changes its function, aliases is degraded. In nan aging brains of mice, we observed that this finely tuned strategy becomes progressively unbalanced: galore labels accumulates and immoderate are moreover lost, sloppy of really overmuch of a peculiar macromolecule is present."
Dr. Alessandro Ori, erstwhile investigation group leader astatine nan FLI
The "recycling system" of nan compartment loses its power
As we age, nan cell's soul "recycling system" besides originates to falter. The proteasome - a molecular instrumentality responsible for breaking down damaged aliases unneeded proteins - gradually loses efficiency. As a result, proteins tagged for disposal pinch ubiquitin commencement to build up successful nan brain, a clear motion that its cellular cleanup machinery is nary longer moving properly. The researchers recovered that astir one-third of nan age-related changes successful macromolecule ubiquitylation successful nan encephalon tin beryllium straight linked to this diminution successful proteasome activity.
"Our information shows that nan reduced expertise of cells to wholly destruct damaged proteins is simply a cardinal system of nan aging brain," summarize Dr. Antonio Marino and Dr. Domenico Di Fraia, some first authors of nan study. "The delicate equilibrium betwixt macromolecule synthesis and degradation shifts - a emblematic characteristic of cellular aging. In nan agelong term, this tin besides impair nan usability of nervus cells successful nan brain."
Diet arsenic a modulator - a hopeful sign
In a further step, nan researchers investigated whether nan ubiquitylation patterns recovered could beryllium influenced by changes successful diet. To this end, older mice were fed a mean fare (calorie restriction) for 4 weeks earlier being returned to a normal diet. The astonishing consequence was that nan short-term alteration successful fare importantly altered nan ubiquitylation shape successful nan mice - successful immoderate proteins, it moreover reverted to nan previous, youthful state.
"Our results show that moreover successful aged age, fare tin still person an important power connected molecular processes successful nan brain," emphasizes Dr. Ori. "However, fare does not impact each aging processes successful nan encephalon equally: immoderate are slowed down, while others hardly alteration aliases moreover increase."
The study frankincense provides caller insights into nan molecular mechanisms of encephalon aging. It suggests that ubiquitylation is simply a delicate biomarker of nan aging processes - and perchance a starting constituent for slowing down age-related harm to nervus cells. In nan agelong term, nan study of these processes could thief to amended understand nan relationship betwixt nutrition, macromolecule balance, and neurodegenerative diseases specified arsenic Alzheimer's disease.
Source:
Journal reference:
Marino, A., et al. (2025). Aging and fare change nan macromolecule ubiquitylation scenery successful nan rodent brain. Nature Communications doi: 10.1038/s41467-025-60542-6. https://www.nature.com/articles/s41467-025-60542-6
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