First published @ Senescent CELL blog
In recent times, scientific findings on cellular senescence have made headlines. The majority of these highly publicized articles are concerned with the potential health benefits of removing senescent cells from our bodies. Destroying senescent cells in mice can reverse aspects of ageing and prevent side effects in response to chemotherapy.
In an attempt to simplify the term "cell senescence" for public consumption, the media incorrectly use words such as "old", "aged" and "elderly" to describe such cells. This is understandable since "senescence" means "to grow old".
The term "senescence" regarding cells was first used over fifty years ago to describe cells that could no longer proliferate after extended time in culture. Without our current understandings, this inability to proliferate was thought to be due to processes related to cell ageing and so such cells were labelled as "senescent". Although now inaccurate, this labeling is still in use today.
So what is the difference between cell "ageing" and cell "senescence"?
Cell ageing results from the accumulation of random damage leading to impairment in cell function with time. Cell ageing may result from the build up of damage to cellular lipids (i.e. peroxidation), damage to proteins leading to altered protein folding and aggregation, damage to the mitochondria resulting in abnormal metabolic processes and changes (epigenetic) to DNA causing alterations in gene expression.
In contrast to cell ageing, cell senescence is a programmed change in cell state often initiated by persistent damage to DNA.
Although the initial factors which trigger DNA damage in cells may itself be random, the accompanying cellular changes associated with cell senescence are not random. In an orchestrated response, cells permanently stop dividing, they secrete molecules that can attract immune cells and express immune proteins on their cell surface. As such, cell senescence can be considered as a mechanism to eliminate unwanted cells by the immune system.
Part of the reason why senescent cells stay in our bodies and promote ageing may be due to a failure in the ability of an aged immune system to kill senescent cells. The molecules that were once beneficial in attracting immune cells now become destructive over time.
Further scientific evidence demonstrating that senescent cells are not "aged" cells but rather a programmed change in cell state, comes from studies on embryonic development.
Two back to back publications in Cell from 2013 demonstrated that the change in cell state associated with senescent cells may be beneficial during embryonic development. If this indeed the case, it is highly unlikely that such cells suddenly become "aged" or "old" to carry out their function. Embryonic development is highly a regulated process. What is more likely is that such senescent cells are indeed programmed and like programmed cell death (apoptosis), play an important role in tissue remodeling during embryonic development.
Telomere shortening: adding further to the confusion
The vast majority of the early studies on cell senescence were focused on cells which stopped dividing after extended proliferation in culture. This was later shown to be due to telomere shortening.
Every time a cell divides it loses a portion of DNA at the end of its chromosomes called telomeres- long repeats of non-coding DNA. Telomeres protect the ends of our DNA, but when they become too short, they can no longer perform this task. This causes the cell to recognize unprotected DNA-ends as damage. A result of this DNA damage signal is induction of cell senescence.
Throughout our lives, cells divide and our telomeres gradually become shorter. There have been numerous studies investigating the correlation between telomere length and chronological age. In parallel to telomere shortening, gradual random alterations associated with cell ageing will also occur.
This relationship between age, telomere length and cell senescence is likely another explanation for why senescent cells are often thought of as "aged" or "old" cells. But even in this instance, cell senescence does not occur gradually over time like ageing cells, but suddenly in response to a very short telomere.
There is little or no evidence suggesting that telomere shortening per se causes ageing. Cells likely function perfectly well with progressively shorter telomeres. Problems only arise when a telomere eventually becomes too short. As such, telomere shortening increases our risk of age-related conditions as cells are more likely to become senescent.
Drugs which could extend the length of telomeres by activating an enzyme called telomerase (which adds lost telomeres back to DNA) could prevent cells from becoming senescent and help prevent ageing.
In summary, cell ageing can be considered as a unprogrammed, random process leading to a gradual decline in cell function. Cell ageing is detrimental to the function of normal biological processes. Cell senescence can be induced randomly, but is a programmed change in cell state that can occur independent of age. Cell senescence can be both detrimental and beneficial depending on the biological context.
