We've long praised dolphins as being one of the most intelligent animals on Earth, but that might come with an unfortunate downside. Oxford researchers studying the brains of dolphins have found clear signs of Alzheimer's disease, marking the first time the illness has been detected in a wild animal. In an interesting twist, the discovery may dash the hopes that an extreme calorie-restricted diet can extend our lifespans.
In most cases, animals die soon after they become infertile with age, because – in the eyes of evolution – once a creature passes on its genes, what's the point of keeping it alive? A handful of species, including humans and dolphins, can live long post-fertile lives, but conditions like Alzheimer's and diabetes might be the price we pay for those twilight years.
Testing that idea was the focus of the new study, and to do so, the researchers looked at the brains of dolphins to see if these long-living creatures also exhibited signs of Alzheimer's. The specimens were found in the wild in Spain, having died after becoming beached.
Sure enough, the researchers found plaques and tangles in the animals' brains – classic calling cards of Alzheimer's. Plaques are deposits of a protein called beta amyloid that build up between neurons, while twisted strands of a protein called tau make up the tangles. Together, these intruders choke out nerve cells and cause the deterioration we know as Alzheimer's.
"It is very rare to find signs of full-blown Alzheimer's disease in non-human brains," says Simon Lovestone, lead researcher on the study. "This is the first time anyone has found such clear evidence of the protein plaques and tangles associated with Alzheimer's disease in the brain of a wild animal."
Alzheimer's and type 2 diabetes both appear to be caused by the same symptom of aging: namely, changes in insulin signalling. Insulin is a hormone that regulates blood sugar levels, and if the body can't produce enough of it or develops a resistance to it, type 2 diabetes can be triggered. Eventually, Alzheimer's may follow.
But insulin signalling can also be manipulated for healthy reasons. In previous work, researchers have tightly restricted the calorie intake of mice, and found that it greatly increases the animals' lifespans. The human body, it turns out, may have evolved this trait naturally, granting us longer lives but saddling us with increased risk of diabetes and Alzheimer's in later years.
"We think that in humans, the insulin signalling has evolved to work in a way similar to that artificially produced by giving a mouse very few calories," says Lovestone. "That has the effect of prolonging lifespan beyond the fertile years, but it also leaves us open to diabetes and Alzheimer's disease. Previous work shows that insulin resistance predicts the development of Alzheimer's disease in people, and people with diabetes are more likely to develop Alzheimer's."
So while it's always helpful to improve our understanding of these illnesses, the discovery comes with some bad news as well. According to the new study, the life-extending benefits of caloric restriction might not translate to humans – nature has likely wrung out all the extra years of life that such a drastic diet could offer.
"If we are right, then it is already too late, by tens of thousands of years," says Lovestone. "That's about how long ago in our evolution we are likely to have acquired the insulin resistance that gained the extended lifespan that calorie restriction would produce. While a sensible diet has obvious health benefits and is important for avoiding premature death from avoidable obesity-related conditions, we think that extreme calorie restriction will not extend the human lifespan."
The researchers hope to use the findings to develop better animal models of Alzheimer's, which can help test new treatments more accurately.
The study was published in the journal Alzheimer's & Dementia.
Source: Oxford University
