Fight Aging!

This popular science article discusses recent research that categorizes age-related changes a few thousand different cell populations in the body, distinguished by transcriptional behavior. This big picture view of aging shows a wide variety of responses to aging between cell types that occur in a staged progression throughout life, which the researchers characterize as a grand remodeling of the society of cells. The principle scientist in question favors a programmed aging viewpoint, but as is always the case, whether one thinks aging is a program like development that is under evolutionary selection or instead an accumulation of damage that occurs because health and fitness in later life is not under strong evolutionary pressure, the actual observations can be made to fit any theory of aging.

In one set of studies, we extracted more than 20 million cells from various organs from mice of different ages: 3, 6, 12, 16, and 23 months - roughly equivalent to 20, 30, 50, 60, and 75 years in humans. We analyzed the expression of 20,000 genes per cell and used this information to define the cell types. Then we tracked their population dynamics. We found that not every cell type gets changed in aging. We identified 536 main cell types and 1,828 subtypes. Only about one-quarter of these subtypes show a strong shift in aging. Others remain stable across the lifespan. It is surprising to find that changes in aging are not universal across all the cells, that there are specific cell populations that are more vulnerable.

We found that aging can be separated into distinct time windows. In each window, specific groups of cells show coordinated dynamics. In the early phase, for example, we see that some cell types are rapidly depleted. This is followed by another phase, in which other cells are greatly expanded. In the first stage, 3 to 6 months in a mouse [about 20 to 30 years in a human], there is a loss of certain fat and muscle cells, and of two immature cell types in the brain that have the capacity to regenerate different types of brain tissue.

Between 6 and 12 months in a mouse [equivalent to a person in their 30s and 40s], we see dramatic depletion of cells needed to maintain the body's tissues. These include tenocytes [the primary component of tendons]; the cells that wrap around blood vessels and stabilize the circulatory system; the smooth muscle cells of the colon; and kidney epithelial cells, which filter toxins from the blood. Also in decline are some immune cells that protect specific tissues such as the intestine.

At around 12 months in mice [roughly 40 to 50 years in humans], there is a shift from cell depletion to cell expansion. The first expansion wave is dominated by immune cells, but also includes select cells in the lungs, kidneys, and other organs whose properties have changed as a result of stress or inflammation. At around 16 months in mice [late 50s and beyond in humans], specialized aging-associated immune cells expand. When these selfish, uncontrolled cells emerge, they will eventually proliferate and destroy the system. In the meantime, they may contribute to the increased risk with age of inflammatory conditions such as heart disease, arthritis, cancer, and chronic respiratory illnesses.

Previously, people saw aging as a linear accumulation of damage to molecules such as proteins and DNA. But we found that aging is not a linear process. It's more like a developmental process, in which there are distinct stages that involve coordinated changes in specific cell types across different organs. Our claim is that aging is not so much molecular damage as a remodeling of the entire cell society.

Link: https://www.quantamagazine.org/why-aging-may-be-a-program-not-a-breakdown-20260814/