Research may reveal why people can suddenly become frail at 70

A groundbreaking theory of aging that explains why people can suddenly become frail after reaching the age of 70 has raised the prospect of new therapies for decline and the diseases of old age.

Cambridge researchers have discovered a process that leads to a ‘catastrophic’ change in blood composition in older people, increasing the risk of blood cancers and anemia, and impairing the effectiveness of white blood cells in fighting infection .

Scientists believe similar changes occur in organs all over the body, from skin to brain, potentially explaining why people often age in good health for decades before experiencing a more rapid decline in their 70s or 80s.

“What’s exciting about this work is that there may be a common set of processes at work,” said study lead author and cancer program manager Dr Peter Campbell. aging and somatic mutations at the Sanger Institute in Cambridge. “Ultimately the goal would be to slow or intervene in the aging process, but at the very least we see an option to use it to measure biological age.”

Aging is a complex process, but many scientists suspect that the gradual accumulation of mutations in cells gradually degrades the body’s ability to function properly. The latest research suggests that thinking is flawed, or at best incomplete, and instead blames “selfish” cells that become dominant in old age.

Working with scientists from the Wellcome-MRC Cambridge Stem Cell Institute, Campbell and his colleagues studied blood cells of all ages, from newborns to people in their 70s and 80s. They found that adults under 65 had a wide array of red and white blood cells produced by a diverse population of 20,000 to 200,000 different types of stem cells in their bone marrow.

Among those over 65, the picture was radically different. About half of their blood cells came from 10 or 20 separate stem cells, greatly reducing the person’s blood cell diversity, with consequences for their health.

Writing in the journal Nature, the researchers explain that while the stem cells involved in making blood accumulate mutations over time, most of those changes are harmless. But problems arise when rare “driver” mutations accelerate stem cell growth, often producing substandard blood cells in exchange. When a person is between 30 and 40 years old, the growth advantage of aberrant stem cells makes little difference, but at age 70 and older, these rapidly growing cells come to dominate blood cell production.

“The exponential growth explains why there’s such a sudden change in frailty after age 70, why aging hits at that kind of age,” Campbell said. Faster-growing blood stem cells are linked to blood cancers and anemia, but also make people less resistant to infections and medical treatments such as chemotherapy.

“What we know from other organ systems is that many of the same observations apply,” Campbell added. The researchers now plan to look for the same process in the skin to understand why aging leads to wrinkles and slower healing.

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Dr Elisa Laurenti, assistant professor at the Wellcome-MRC Cambridge Stem Cell Institute and joint principal investigator on the study, said chronic inflammation, smoking, infection and chemotherapy could all produce stem cells with mutations carcinogenic.

“We predict that these factors also advance the decline in blood stem cell diversity associated with aging,” she said. “It is possible that certain factors also slow down this process. We now have the exciting task of understanding how these newly discovered mutations affect blood function in the elderly, so that we can learn how to minimize disease risk and promote healthy aging.

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