Today's open access review covers what is known of cellular senescence as a cause of aging, and is a very readable example of the type. It is always pleasant to find a well-written paper that can serve as an introduction for people outside the scientific community, those with an interest in the topic but only a little knowledge of the relevant biology. If you have friends who fit that description, and who are not all that familiar with the science, then you might send this over as a more gentle introduction than some of the other reviews of cellular senescence published in recent years. In particular, you might point out the middle section from which I borrowed the title for this post.

Senescent cells are those that have entered an altered state in which replication is shut down, and a range of signals and other molecules are secreted. These provoke inflammation, attract immune cells, remodel the nearby extracellular matrix, and increase the likelihood of nearby cells also becoming senescent. Senescence has several forms, occurring in response to cell damage, a toxic environment, radiation, or in the vast majority of cases as the end state of a somatic cell that has reached the Hayflick limit on cell divisions. Most species have a two-tier hierarchy of cells: a small number of stem cells that can replicate indefinitely, and the limited somatic cells that make up the vast majority of any tissue. Stem cells produce a supply of somatic cells to make up those lost to the Hayflick limit. In such a system something like senescence has to exist if somatic cells are in fact to be limited in the number of times they can replicate. Why does this two-tier system exist? Probably because it is the most accessible way to suppress the risk of cancer sufficiently well for higher animal life to evolve at all: if any more of our cells were normally capable of unlimited replication, and thus easily subverted by cancerous mutations, then our lineage could not survive over evolutionary time.

Beyond the necessity of being a full stop at the end of a somatic cell's life span, cellular senescence appears to have evolved other uses along the way. Reuse is very common in biology. Thus cellular senescence acts to set limits to growth in embryonic development, coordinates with the immune system in wound healing, and acts to suppress cancer, at least when the number of senescent cells is still low, by shutting down replication in cells that are most at risk of becoming cancerous. Senescent cells so far appear to be best as short-lived entities that self-destruct or are destroyed by the immune system quite quickly after they appear. The contribution of senescent cells to aging is produced by the tiny minority of such cells that somehow linger instead. The signals they secrete, used in the short term to carry out their evolved tasks, become destructive when issued over the long-term, and in ever increasing volume. The solution to this problem is likely very simple: destroy these cells, clearing up the remnant population that natural processes fail to eliminate. Doing so will reverse this one portion of the aging process.

Senescence in the aging process