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The secret to becoming a centenarian may be within the immune system. Rob and Julia Campbell/Stocksy
  • As human life expectancy has increased, so has the number of people living to 100 years of age or older.
  • Researchers have found that centenarians have a unique immune cell composition and activity, giving them an immune system that helps them live longer.
  • Scientists believe these findings may be used to develop healthy aging therapeutics.

The life expectancy of humans on our planet has more than doubled since 1900. Global life expectancy has increased from 31 years in 1900 to 73.2 years in 2023, and is expected to further increase to 77.1 years in 2050.

Also increasing is the number of people reaching the age of 100 or more. Known as centenarians, researchers estimate there were about 450,000 centenarians globally in 2015, with that number projected to increase to 3.7 million in 2050.

Previous research in the early 2000s estimated that globally, the number of people living to 100 years or older would more than quintuple between 2005 and 2030.

One thing still unknown is what allows some people to live into their 100s, while others do not.

Led by researchers from Tufts Medical Center and Boston University School of Medicine, a new study is helping to answer this question by finding that centenarians possess a unique immune cell composition and activity, giving them a highly-functional immune system and allowing them to live longer.

Scientists believe these findings could be used potentially to develop healthy aging therapeutics.

The study was recently published in the journal Lancet eBioMedicine.

As we age, all parts of the body experience changes, including the immune system.

According to Dr. Scott Kaiser, a geriatrician, and director of Geriatric Cognitive Health for the Pacific Neuroscience Institute in Santa Monica, California, there are two main concepts when it comes to how the immune system changes as we get older.

“One is immunosenescence and that’s the age-related process of immune dysfunction,” he explained to Medical News Today.

“So changes in our immune system composition and function over time can lead to poor immune function in older people. And that’s closely related to people’s vulnerability to infection, autoimmune disease, and even various types of cancer,” he said.

“And then there’s this issue of inflammaging, which is a term that’s been used to describe age-related increases in inflammation because of high levels of pro-inflammatory markers in the blood and different tissues in the body. That’s a strong risk factor for all sorts of diseases, including neurodegenerative processes like Alzheimer’s disease, for example,” Dr. Kaiser continued.

“So there’s a lot to look at in terms of the immune function over time and how our immune systems changes with age may either make us more vulnerable or protect us,” he added.

According to Dr. Tanya Karagiannis, a senior bioinformatician at the Center for Quantitative Methods and Data Science in the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, and lead author of this study, she and her team decided to study the immune systems of centenarians because with age comes changes in our immune systems including in their function and cell makeup, and these changes can lead to aging-related diseases.

“Many centenarians experience delays in the onset of aging-related disease and this suggests the presence of an elite immunity that continues to remain highly functional even at extreme old age,” she told Medical News Today.

For this study, researchers performed single-cell sequencing on a category of immune cells called peripheral blood mononuclear cells (PBMCs) from blood samples taken from seven centenarians enrolled in the New England Centenarian Study.

“We used single-cell data and applied new computational methods to analyze immune cells that circulate through the immune system across the human lifespan. We looked at differences in the presence of specific immune cell types across younger ages and extreme old age and found cell type-specific changes in aging and extreme old age,” Dr. Karagiannis explained.

“We also took the same cell types and explored the differences in gene expression across ages to discover different gene expression patterns of extreme longevity that change with age but also are unique to extreme old age,” she added.

Upon analysis, the researchers confirmed observations made in previous studies of aging that identified unique cell type-specific compositional and transcriptional changes only found in centenarians that reflect normal immune response.

They also found centenarians had cell type signatures specific to exceptional longevity in both genes with age-related changes and genes expressed uniquely in centenarians.

“We were not as surprised to find genes that change with age in centenarians since they are an aging population. What was surprising was the different aging patterns we identified including genes that were aging-specific in which expression levels changed with age but not in extreme longevity across various cell populations,” Dr. Karagiannis said.

“Our findings can provide a foundation to explore potential drivers of extreme old age that could lead to the discovery of healthy aging therapeutics. We would like to explore longitudinal changes in immune cells of centenarians and younger aged individuals to help better define the protective drivers of extreme longevity that provides the beneficial health outcome observed in these individuals,” she continued.

After reviewing this study, Dr. Kaiser told Medical News Today he found this study interesting as it actually looked at people who have aged extremely well, who have defied age, so to speak, and then looked at what’s going on in them to see if we can learn anything.

“The potential lessons here are in what makes us more resilient,” he explained.

“Looking at these people who had extreme longevity, living into 100s and even beyond, and figure out what is the nature, what is the characteristic of their immune system so that we could better understand what might be going on, and then figure out how that could be translated into potential therapies for other people, so that more people can enjoy that.”
— Dr. Kaiser

MNT also spoke withKathleen Cameron, senior director of theNational Council on Aging’s Center for Healthy Aging, about this study.

She said understanding the immune changes that come with aging is important to help people live longer. And a lot of people want to live longer if they can also be healthy.

“If we can determine what is creating this immune resilience for those who live over 100, that can lead to treatments that can help people live longer. Or, if there are certain healthy behaviors that lead to this resilience, that would also help us,” Cameron continued.

However, she said this is all very preliminary research, as this study was small, and it should lead to other studies to help healthcare practitioners better understand this immune resilience.

“More research is needed to understand the effect these immune patterns have on longevity. Is there something in the centenarians’ family history or other things that happened in their life, exposure to certain things that might have changed their immune system? We don’t know that from this study. Knowing more about this could lead to new therapies or new ways to improve the immune system.”
— Kathleen Cameron