Brain aging

Men with “long-life” genes had less small-vessel damage in their brains at 70

In 675 Swedish 70-year-olds, a genetic score for living long was not linked to brain structure overall. In men only, a higher score went with fewer signs of damage to the brain's small blood vessels and a slightly thicker cortex in three regions. The authors say the findings must be confirmed before much is read into them.

Some people inherit a slightly better chance of reaching a great age. A Swedish study asked whether that genetic advantage shows up in the brain at 70. Across everyone, it didn't. But in men, those with a higher genetic "longevity score" had fewer signs of damage to the brain's tiny blood vessels. It is a modest, single-cohort finding that the authors themselves want confirmed.

Genes play only a partial role in how long we live: the paper cites estimates of 10–25% for reaching your seventies and around 60% for becoming a centenarian. Large gene studies have found many DNA variants that are a bit more common in very long-lived people. Adding up how many of these a person carries, each weighted by its effect, gives a polygenic score. The best-known single gene here is APOE: one version, APOE4, raises the risk of Alzheimer's disease and shortens survival.

As the brain ages, the outer layer of grey matter (the cortex) thins, and scans start to show bright spots in the white matter called white matter hyperintensities. These, together with tiny old bleeds, small silent infarcts and widened fluid spaces, are signs of small vessel disease, wear and tear of the brain's smallest blood vessels.

What they did

  • In 2014, Gothenburg invited a sample of all residents born in 1944. Of those who took part, 675 had usable brain scans and DNA data after excluding people with dementia, stroke and some other neurological diseases.
  • The team built two longevity scores from a large earlier gene study (which didn't include these participants): one with the APOE region and one without it.
  • From the MRI scans they measured grey and white matter volume, cortical thickness, deep brain structures, the integrity of white-matter fibre tracts, the volume of white matter hyperintensities, and a radiologist's small-vessel-disease score.
  • They checked whether the results differed between men and women and corrected for the many comparisons made.

What they found

  • No link in the whole group. Across all 675 people, neither score was related to any of the main brain measures.
  • Men: healthier small vessels. In the 327 men, a higher score (either version) went with a smaller volume of white matter hyperintensities and lower odds of a high small-vessel-disease score: about 37% lower odds per step up in the score (one standard deviation).
  • Men: a slightly thicker cortex in three areas. Two parts of the frontal lobe involved in language (the pars triangularis and pars opercularis) and the insula, which helps regulate the body's internal state.
  • Not just APOE. The score without the APOE region showed much the same pattern, so other longevity genes seem to matter too.
  • Women: nothing. No links were found in the 348 women.
  • Partly through blood pressure and the like? Taking into account education, smoking, high blood pressure, weight, diabetes and high cholesterol weakened some of the vessel links; one (the score without APOE and small-vessel damage) remained.

What to keep in mind

  • No overall effect. The authors stress that because nothing showed up in the whole sample, the male-only findings "must therefore be interpreted carefully until confirmed in other studies".
  • Fragile results. Some links disappeared depending on how the data were analysed: for example, when the small-vessel score was used on its full 0–4 scale rather than split into low and high.
  • One snapshot. Each person was scanned once. Genes are present from birth, so the brain can't have changed them, but the study can't show how the brain changed over time.
  • A healthy, narrow group. All were 70, of European ancestry, from one Swedish city, and the people who had scans were healthier and more educated than those who didn't.
  • Scores explain little. Longevity scores capture only a small part of the variation in how long people live.
  • Why only men? Men in the sample had more small-vessel damage to begin with, which may have made a link easier to detect; the reasons are speculative.

Why it matters

The finding fits a simple idea: part of what "long-life genes" do may be to keep blood vessels healthy, including the tiny ones in the brain. An earlier study, which the authors cite, also linked such scores to fewer white matter hyperintensities in men only. Genes can't be changed, but blood-vessel risk factors like high blood pressure can, which is why the authors see their results as further support for detecting and treating vascular risk factors to help keep the brain healthy. For now, the brain-structure results are a clue to check in other cohorts, not an established fact.

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