The human brain appears to undergo accelerated ageing once a person reaches the age of 44, with the deterioration hitting a peak around 67 and plateauing around 90, according to a new study.
A better understanding of these critical transition points may lead to new interventions against neurological conditions like Alzheimer’s, researchers say.
“Understanding exactly when and how brain aging accelerates gives us strategic time points for intervention,” said Lilianne Mujica-Parodi, lead author of the study from Stony Brook University (SBU).
The study, published in the journal PNAS, assessed the communication between brain regions in over 19,300 individuals across four large-scale datasets.
It found that brain networks degrade in a nonlinear trajectory with clear transition points – rather than a late-life clinical onset or a gradual linear decline as previously thought.
The research follows previous findings that signal transmission by the brain’s neurons is impacted by a loss of energy within the nerve cells.
“We’ve identified a critical midlife window where the brain begins to experience declining access to energy but before irreversible damage occurs, essentially the ‘bend’ before the ‘break,’” said Dr Mujica-Parodi, who is the director of SBU’s Laboratory for Computational Neurodiagnostics (LCNeuro).
During midlife, the brain’s nerve cells continue to function despite being metabolically stressed due to insufficient fuel, researchers say.
This stress is mainly due to insulin resistance within the nerve cells, scientists found.
“However, by later ages, neurons’ prolonged starvation may have triggered a cascade of other physiological effects,” Dr Mujica-Parodi explained.
“Therefore, providing an alternative fuel during this critical window can help restore function,” she said.
Scientists found that the metabolic stress experienced by neurons is consistently followed by inflammatory ones as well as changes within blood vessels supplying nutrients to the brian.
Researchers discovered two key proteins – insulin-dependent glucose transporter GLUT4 and the known Alzheimer’s risk factor APOE – are implicated in these aging patterns.
However, they also found that another protein – neuronal ketone transporter MCT2 – could be a protective factor in preventing stress from these changes.
The study suggests MCT2 could serve a beneficial role in enhancing the brain’s ability to utilise ketones – an alternative brain fuel that neurons can metabolise without insulin.
In another experiment, scientists administered careful doses of glucose and ketones to 101 participants at different stages along their aging trajectory.
They found that unlike glucose, the ketone molecules effectively stabilised deteriorating brain networks with effects that differed significantly across critical age transition points.
For instance, while ketones showed moderate benefits in young adults, the molecules were found to have maximum benefits during the midlife “metabolic stress” period between 40 and 59 years.
These findings can “revolutionise” approaches to preventing neurodegenerative diseases like Alzheimer’s, scientists say.
With dementia cases projected to triple by 2050, new insights from the study offer hope for preventive strategies, researchers say.
A metabolic intervention developed from the findings, such as ketogenic diets or supplements, might start working “well before cognitive symptoms appear” as opposed to current treatments that typically target symptoms only after they emerge.
“This represents a paradigm shift in how we think about brain aging prevention,” said Botond Antal, another author of the study.
“Rather than waiting for cognitive symptoms, which may not appear until substantial damage has occurred, we can potentially identify people at risk through neurometabolic markers and intervene during this critical window,” Dr Antal said.
