Longevity: Aging Cells vs Cell Senescence

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 aging 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”.
Aging senescent cells

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 aging and so such cells were labeled as “senescent”.  Although now inaccurate, this labeling is still in use today.

So what's the difference between cell “aging” and “senescence”?

Cell aging results from the accumulation of random damage leading to impairment in cell function with time.  Cell aging 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 aging, 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 aging 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, which are 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 the 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 aging 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 aging cells, but suddenly in response to a very short telomere.
There is little or no evidence suggesting that telomere shortening per se causes aging.  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 aging.

Peptides – The New Scientific Frontier

One of the most studied peptide is Epitalon (actually it's a tetrapeptide, with a four amino acid chain). Its benefits ignited an entire field of study for health and longevity. Now peptides are being studied in vast areas in science and medicine.

A peptide is defined as two or more bonded amino acids. Peptides are precursors to proteins, which require at least 50 bonded amino acids. In addition to performing a host of essential functions in the body, peptides may have formed the basis for cellular life on Earth.

Peptides occur naturally in every cell of every living thing. They have a number of functions, including the production of enzymes to help your body break down foreign substances, and create antibiotics for your immune system and hormones that control everything from growth to sexual development. Without peptides, life would not be possible.

Studies show that Epitalon not only reactivates telomerase and thus extends a cell's life, but that it also reduces rates of DNA mutation, prevents degradation of immune function, promotes the health of the intestinal mucosa, and protects nerves from damage in rodent models. In other words, epitalon extends both lifespan and healthspan (the number of years without disease or disability).

You can read more about Epitalon, here, and it can be obtained, now, through OceansLab!

In summary, cell aging can be considered as a unprogrammed, random process leading to a gradual decline in cell function.  Cell aging 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.
Resources:
ncbi.nlm.nih.gov

wikigenes.org

1. Khavinson VK, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity & telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2.
2. Hekimi S, Lapointe J, Wen Y. Taking a “good” look at free radicals in the aging process. Trends In Cell Biology. 2011;21(10) 569-76.
3. Anisimov VN, Arutjunyan AV, Khavinson VK. Effects of pineal peptide preparation Epithalamin on free-radical processes in humans and animals. Neuro Endocrinol Lett. 2001;22(1):9-18.
4. Anisimov VN, Khavinson VK, Provinciali M, Alimova IN, Baturin DA, Popovich IG, et al. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumours in HER-2/neu transgenic mice. Int J Cancer. 2002 Sep 1;101(1):7-10.
5. Anisimov VN, Khavinson VK, Popovich IG, Zabezhinski MA. Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats. Cancer Lett. 2002 Sep 8;183(1):1-8.
6. Kossoy G, Zandbank J, Tendler E, Anisimov V, Khavinson V, Popovich I, et al. Epitalon and colon carcinogenesis in rats: proliferative activity & apoptosis in colon tumors & mucosa. Int J Mol Med. 2003 Oct;12(4):473-7.

Related Posts