Scientists explore hookworm proteins as potential treatment for inflammation

It's been a long-accepted reality that with age comes increased inflammation – so widely accepted it's been dubbed "inflammaging." With this increase in age-related chronic inflammation also comes serious health concerns, such as cardiovascular disease and Alzheimer's. But according to new research, inflammaging isn't as universal of an experience as previously thought.

Published today in Proceedings of Royal Society B, "Inflammaging is minimal among forager-horticulturalists in the Bolivian Amazon," the work highlights little inflammaging in one non-industrialized community, and notably found an increase of inflammation with moderate levels of modernization in another.

Led by Jacob Aronoff – a postdoctoral research scholar at Arizona State University's School of Human Evolution and Social Change, affiliate with the Institute of Human Origins and a member of the Center for Evolution and Medicine – the study looked at two communities in the Bolivian Amazon: the Tsimane and Moseten. 

The Tsimane are a community of more than 17,000 people across 90 villages in the lowlands of the Bolivian Amazon. Living a hunter-farmer lifestyle, their everyday life is very similar to human life prior to the Industrial Revolution. This offers a unique glimpse into the health and aging processes for humans before modern-day influences came into play. Previous research has shown that they have the healthiest hearts and lowest rates of Alzheimer's and dementia in the world.

Benjamin Trumble, senior author on the article and professor in ASU's School of Human Evolution and Social Change, serves as the co-director of the Tsimane Health and Life History Project. The group has a longstanding relationship with the Tsimane to collect demographic and biomedical data, as well as helps to provide medical care for the community – a relationship that has been in effect for more than 20 years. 

This latest look into our human past set out to determine if the inflammation we experience in old age is a universal, human experience. 

To see if they develop inflammaging, we measured a collection of cytokines in a sample of older Tsimane adults to see if they increase with age – we found minimal increases with age."

Jacob Aronoff, postdoctoral research scholar at Arizona State University's School of Human Evolution and Social Change

To deepen their findings, the researchers also examined the Moseten. Although genetically very similar to the Tsimane, the Moseten underwent significant cultural change beginning 300 years ago when Jesuit missionaries settled among them.

"They're still the same genetic group, same language group, but the Moseten now have running water, electricity and indoor plumbing," said Trumble, who is also a research scientist with ASU's Institute of Human Origins and core faculty of the Center for Evolution and Medicine.

"They're kind of in an in-between place where they aren't as industrialized as people living in the U.S., but they aren't as traditional as a population like the Tsimane that's still living much more like most of our human ancestors."

This in-between stage of modernization provides an interesting opportunity of comparison for the researchers.

"We measured them together in the same lab, using the same technology, and we found clearly more pronounced inflammaging in the Moseten, suggesting that inflammaging – to a large extent – is a product of industrialized lifestyles," Aronoff said.

Inflammation isn't the guarantee with age as previously thought. While more research is needed, it does appear to largely be impacted by environmental and lifestyle factors, such as diet and exercise. It also shows that even slight modernization has an impact on deviating the human body from its ancestral path. 

"For 99% of human history we were physically active hunter gatherers. Now with sedentary urban city life we are basically operating outside the 'manufacturer's recommended warranty' right now," Trumble said. 

"By working with populations that are living a more traditional lifestyle, we can get a better idea of what the baseline for human health is."

Other possibilities could be high parasitic and pathogen exposure, something lacking in industrialized communities, but common for the Tsimane. While more research is needed, the immune system response developed from parasitic exposure may play a role in the Tsimane's lack of age-related inflammation. 

"We've eliminated most of our parasites, and that's a good thing. We should keep it that way," said Trumble.

But there may be a way we can harness the potential without the negative impact. 

"One of the things that we could do in the future, potentially, is instead of, say people getting infected with hookworm, we could figure out what are the proteins on the surface of hookworm cells – and what if we could turn that into a drug that people could take and trick our immune system. Our immune system would think we had that problem, and then it would develop differently to fight that off."

Much like how we utilize vaccinations for viruses like the flu, where a controlled pathogenic exposure boosts an immune system response to fight off a natural exposure, the same may one day be true for our age-related inflammation.

Ultimately, though, there is no "silver bullet," according to Trumble, as lifestyle and diet are also likely major contributors to inflammaging. 

"We have future studies underway to look at diets, physical activity and infectious exposures that the Tsimane are infected with that can have these anti-inflammatory effects. We're going to have to do a lot of future studies to figure out what, exactly, are all the factors and how they work together," explained Aronoff.