Genes which play a key role in keeping our minds sharp gradually begin to turn off as we age, research has found.
Brain samples were analysed
Scientists at the Children's Hospital in Boston hope the discovery could lead to new ways to preserve brain function and ward off Alzheimer's disease.
They used a sophisticated screening technique to analyse brain samples from 30 people aged 26 to 106 at post-mortem.
The research is published in the journal Nature.
Lead researcher Professor Bruce Yankner said: "We found that genes that play a role in learning and memory were among those most significantly reduced in the ageing human cortex.
"These include genes that are required for communication between neurons."
Gene activity was assessed by measuring the amount of proteins that they produce.
Protein levels were reduced in older individuals - and changes seemed to start for some in their 40s.
However, the rate of deterioration seemed to vary between individuals.
Compared with the gene patterns of young brains, those of people aged from 40 to 70 were much more variable.
Some middle-aged individuals had "young" genes while others were old before their time.
The researchers believe brain genes are particularly vulnerable to toxins in the environment, and to charged oxygen molecules called free radicals which are released by chemical reactions in the body.
In addition to a reduction in activity in genes important for thought processes, they found evidence of greater activity among genes associated with stress and repair mechanisms and genes linked to inflammation and immune responses.
This suggests that the ageing brain has to try to cope with increasing levels of damage.
Professor Yankner said: "The brain's ability to cope with these toxic insults and repair these genes declines with age.
"It will now be important to learn how to prevent this damage, and to understand precisely how it impacts brain function in the elderly."
Dr Yankner said it had already proved possible to repair ageing genes in the laboratory - but he stressed much more work was required to achieving the same effect in a living human brain.
Rebecca Wood, chief executive of the Alzheimer's Research Trust, described the research as producing "some potentially very important results".
She said: "The genes which the researchers found to be damaged may give us valuable insights into the mechanisms of ageing.
"The evidence of varied rates of ageing between different people in middle age is also exciting as it may suggest means of postponing or slowing the process."
However, she said the techniques used in the study were relatively new, and more work was needed to assess the validity of the findings.
"Not enough is yet known about the multiple functions of the genes they have picked out.
"Further studies should also include cases of Alzheimer's to see if the same or different genes are affected in ageing to those in the disease.
"However, this is an exciting step which could lead to real progress in understanding the ageing of the brain and of its degeneration in the tragic disease of Alzheimer's."
Professor Clive Ballard, director of research, Alzheimer's Society, said: "This work is likely to initiate a variety of productive research strategies, including approaches to look at the protection of gene function.
"It also provides a scientific framework to reinforce the potential therapeutic value of antioxidants such as vitamin C, green tea and red wine that 'mop-up' free radicals."