It's about aging: The secret of blood aging after 70 years old is revealed

How do genetic changes that slowly accumulate in blood stem cells throughout a person's life lead to dramatic changes in blood production after the age of 70? A new study may provide some insights. The study, published in the journal Nature and conducted by scientists at the Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute and collaborators, proposes a new theory of aging.

All human cells undergo genetic changes throughout life, known as somatic mutations. Aging is likely caused by multiple types of damage that accumulate in our cells over time. One theory is that the accumulation of somatic mutations causes cells to gradually lose their functional reserve. However, it is unclear why this gradual accumulation of molecular damage leads to a sudden deterioration in organ function after age 70.

To understand this aging process, the research team studied the production of blood cells in the bone marrow and analyzed 10 individuals ranging in age from newborns to the elderly. They sequenced the whole genome of 3,579 blood stem cells and identified all somatic mutations contained in each cell. The team used it to reconstruct the "family tree" of each person's blood stem cells, showing for the first time the relationships between blood cells and how these relationships change during the human life cycle.

The researchers found that these "family trees" changed dramatically after the age of 70. The blood cells produced by adults under the age of 65 come from 20,000 to 200,000 stem cells, each of which contributes roughly the same amount, and most of them belong to clonal hematopoiesis. In contrast, the blood cell production of people over the age of 70 is very different, and the clonal diversity decreases significantly. The number of clonal expansions per individual is 10 to 20, accounting for as much as 30%-60% of the total hematopoiesis. The number of these highly active stem cells gradually increases throughout the life of the subjects, which is caused by a rare subset of somatic mutations called "driver mutations."

These findings led the team to propose a model in which age-related changes in blood production arise from somatic driver mutations that cause "selfish" cloned stem cells to dominate the bone marrow of older people and increase in many other tissues of their bodies with age. This increases the risk of cancer and may also lead to other functional changes associated with aging. This also causes the diversity of blood stem cells to be lost in old age, resulting in an impairment of the stem cells' ability to generate functional mature blood cells.

The study also showed that which clone dominates varies from person to person, so the model also explains changes in disease risk and other characteristics in older people.

Dr Elisa Laurenti, Assistant Professor at the Wellcome-MRC Cambridge Stem Cell Institute and co-senior researcher on the study, said: "Factors such as chronic inflammation, smoking, infection and chemotherapy can lead to the earlier development of clones carrying cancer-causing mutations. We predict that these factors will also lead to the decline in blood stem cell diversity associated with ageing. However, there may also be factors that slow this process down. There is now an exciting task to work out how these newly discovered mutations affect blood function in older people, so that we can learn how to minimise disease risk and promote healthier ageing."