The cellular secrets of aging revealed by researchers |  Health

The cellular secrets of aging revealed by researchers | Health

New research has revealed how genetic changes that slowly accumulate in blood stem cells throughout life are likely to be responsible for the dramatic change in blood production after age 70. The study, led by scientists from the Wellcome Sanger Institute, Wellcome-MRC Cambridge Stem Cell Institute and collaborators, is published today (June 1) in the journal Nature, and offers a new theory of aging.

All human cells acquire genetic changes throughout life, called somatic mutations. Aging is likely caused by the accumulation of several types of damage to our cells over time, one theory being that the accumulation of somatic mutations causes cells to gradually lose their functional reserve. However, it is currently unknown how such a gradual accumulation of molecular damage could translate into a sharp deterioration in the functioning of our organs after the age of 70. To study this aging process, the team from the Wellcome Sanger Institute, Cambridge Stem Cell Institute and collaborators studied the production of blood cells from the bone marrow, analyzing 10 individuals ranging in age from newborns to the elderly. They sequenced the entire genomes of 3,579 blood stem cells, identifying all the somatic mutations contained in each cell. The team used it to reconstruct ‘family trees’ of each person’s blood stem cells, showing, for the first time, an unbiased view of the relationships between blood cells and how those relationships change throughout life. human life.

The researchers found that these “family trees” change dramatically after the age of 70. Blood cell production in adults under 65 increased from 20,000 to 200,000 stem cells, each of which contributed in roughly equal amounts. In contrast, blood production in individuals over the age of 70 was very uneven. A reduced set of expanded stem cell clones – as few as 10 to 20 – contributed up to half of all blood production in each elderly person studied. These highly active stem cells gradually multiplied throughout that person’s lifetime, due to a rare subset of somatic mutations called “motor mutations.” These findings led the team to propose a model in which age-associated changes in blood production stem from somatic mutations causing ‘selfish’ stem cells to dominate in the bone marrow of the elderly. This model, together with the regular introduction of motor mutations that cause the growth of functionally altered clones over decades, explains the dramatic and inevitable shift to reduced diversity in blood cell populations after the age of 70. The clones that become dominant vary from person to person, and so the model also explains the observed variation in disease risk and other characteristics in older adults. A second study, also published today in Nature, explores how different individual driver mutations affect cell growth rates over time.

Dr Emily Mitchell, Registrar of Hematology at Addenbrooke’s Hospital, PhD student at the Wellcome Sanger Institute and principal investigator of the study, said: “Our results show that blood stem cell diversity is lost with age due to positive selection of faster growing cells. clones with driver mutations. These clones “outperform” slower growing ones. In many cases, this improved fitness at the stem cell level likely comes at a cost – their ability to produce functional mature blood cells is impaired, which explains the observed age – related loss of function in the blood system. Dr Elisa Laurenti, Assistant Professor and Wellcome Royal Society Sir Henry Dale Fellow at the Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, and Joint Principal Investigator on this study, said: “Factors such as inflammation chronic smoking, infection, and chemotherapy cause earlier growth of clones carrying carcinogenic mutations.We predict that these factors also promote the decline in blood stem cell diversity associated with aging.It is possible that there is also factors that slow 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 the risk of disease and promote healthy aging.

Dr Peter Campbell, head of the cancer, aging and somatic mutations program at the Wellcome Sanger Institute and principal investigator on the study, said: “We have shown, for the first time, how the regular accumulation of mutations throughout life leads to catastrophic catastrophe. and inevitable change in blood cell populations after age 70. What’s super exciting about this model is that it could apply to other organ systems as well. selfish clones with driver mutations develop with age in many other tissues of the body — we know this may increase cancer risk, but it could also contribute to other functional changes associated with aging.” This research was funded by Wellcome and the William B Harrison Foundation.(ANI)

(This story has not been edited by the Devdiscourse team and is auto-generated from a syndicated feed.)

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