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Becoming Immortal: Senescence, Cancer, and Cellular Aging

Written by Elisa Dong '24

Edited by Alyssa Steinbaum '23

Illustration by Ashley Choi '23

It is a long-held rule that all living organisms must age. A loss of physiological function leads to decreased fertility and, eventually, death, yielding their removal from the vicious current of natural selection. And yet in 1951, the first immortal cell line in history was created using a tissue sample from Henrietta Lacks. An immortal cell line is exactly what it sounds like: a selection of cells modified to replicate indefinitely, allowing them to be cultured in lab for generations. These cells are (almost) immortal beings made to survive and proliferate by our own careful treatment, destined to outlive even our grandchildren if everything goes right.

The strength of this modification raises a fascinating question: if cells can be proven to live forever in immortal cell lines, then why don’t ours do the same? Why must the cells in our bodies grow “old”?

The answer for our mortality can be identified on the cellular level through a process called senescence. In 1965, Leonard Hayflick discovered that typical, non-transformed human cell strains in vitro could only divide a limited number of times [1]. Upon reaching this limit, they would enter permanent cellular growth arrest—alive, but aged.

There are mountains of evidence linking senescence to aging on a physiological level. Senescence is often characterized by the expression of gene p16Ink4a, a tumor-suppressor gene whose frequency in human skin reflects biological age; the younger the person, the fewer p16Ink4a-positive cells [2]. In addition, researchers found that inducing apoptosis in the senescent cells of mice extended their median lifespan [3]. The removal of these aged cells even improved tissue repair and regeneration, a primary concern of aging organisms [4, 5].

Progression to senescence is shaped by the deterioration of telomeres, repeated DNA sequences of TTAGGG nucleotides that cap the end of chromosomes. Our DNA polymerases are unable to begin replication from the very end of a strand, so there is always a bit of material at the end that gets cut off between parent and daughter each time a cell divides. Much like a shoelace cap prevents the ends of the fibers from fraying, the telomeres act as buffers to prevent the chromosomes from shortening with each replication.

Telomeres decrease in length with a cell’s age, allowing them to serve as both a mitotic and aging clock. Each successive division sends grains of sand tumbling down the neck of the hourglass. When the pile settles at the bottom, the cell’s time has run out: it can no longer replicate without losing its genetic data. It ages; it enters senescence. According to Hayflick’s experiment, a normal human embryonic cell carries out fifty cycles before it reaches the aptly named ‘Hayflick Limit.’ [1].

In the 1980s, Elizabeth Blackburn, Carol Greider, and John Szostak discovered telomerase, an enzyme capable of extending the caps on telomeres—and thus extending cells’ lifespans [6]. Reproductive cells like stem cells express this enzyme, accounting for their ability to replicate indefinitely. Some have described this as a way to restart the aging clock, freshly transporting the grains of sand back to the top of the hourglass for our offspring. What if we could apply this to our own bodies? If most patients suffering from aging-related illnesses experience telomere degradation, cellular senescence, and chromosomal instability, why not use telomerase as a therapeutic?

It turns out our own cells can develop the ability to replicate indefinitely, the same way they do in immortal cell lines; this phenomenon simply happens to be one of humanity’s greatest biological enemies—cancer.

Cancer cells, which have broken free from the cell cycle’s regulations, replicate incessantly with little regard for the rest of the organism’s survival. As it turns out, the expression of telomerase is deeply intertwined with the development of cancer; research estimates that telomerase upregulation is a critical feature in 90% of all cancers [7]. Cancer cells that don’t activate telomerase often fail to immortalize, dying when their chromosomes stick together and shatter during cell division [6]. Telomere shortening is not just a hallmark of aging, but an evolutionary anti-cancer mechanism. Many cancer therapies today target the telomerase gene in tumorous cells specifically to eliminate the immortality that makes them so dangerous [8]. Being born with long telomeres improves aging prospects, but may place one at higher risk of oncogenesis [9].

The push and pull concerning telomere length and telomerase expression is a fantastic example of antagonistic pleiotropy. In 1957, George C. Williams coined the term to explain the evolutionary origins of aging. He suggested that the cost of aging was exchanged for increased fertility and survival early in life, all for the sake of natural selection [10]. The genetic tug of war between cancer and late-life aging strongly supports this hypothesis.

As a final experiment, let us suppose that treatment has been perfected, and cancer no longer serves as a threat. Could we then develop human immortality? In 2017, Paul Nelson and Joanna Masel devised a mathematical model explaining why it simply wouldn’t be possible. Even if we could stop senescence from happening, they argued, our multicellularity is the real damning factor. As their article states, “the fitness of a multicellular organism depends not just on how functional its individual cells are but also on how well cells work together” [11].

Aging is not as simple as this article may make it seem. Some organisms find ways to circumvent it through their own unique methods, and others age so slowly their degradation is nearly imperceptible. For instance, the jellyfish Turritopsis nutricula transforms back into its juvenile form after achieving sexual maturity, essentially resetting its age [12]. In plant cells, the germline and somatic cells never really separate, explaining why branch cuttings can yield entirely new trees [13]. Studying the downfalls of all the fellow organisms aging (or not aging!) alongside us can provide us with colorful information about the biological nature of growing old.

New information on telomerase is constantly being uncovered. Severe cases of COVID-19, for instance, have been associated with shortened telomeres. Researchers have hypothesized that this consequence of viral infection explains why many patients experience prolonged issues with tissue regeneration [14]. Some research even finds that telomeres are susceptible to environmental pollutants, explaining why the telomeres of some children shorten faster than others [15].

In the biomedical field, scientists are grappling with the challenge of developing regenerative therapies and cancer treatments that do not break the balance. Immortality may be out of reach for us, but grasping at the mechanisms behind aging and cancer helps us develop ways to counter them both. Many future regenerative, anti-aging therapies, as well as cancer therapies, will originate from the same principles surrounding cellular senescence and telomere shortening. Little by little, we are finding ways to pull apart our evolutionary biological machinery—and put it back together in ways bound to augment our lives.



[1] Hayflick L. The limited in vitro lifetime of human diploid cell strains. Experimental Cell Research. 1965 Mar 1;37(3):614–36.

[2] Waaijer MEC, Parish WE, Strongitharm BH, van Heemst D, Slagboom PE, de Craen AJM, et al. The number of p16INK4a positive cells in human skin reflects biological age. Aging Cell. 2012 Aug;11(4):722–5.

[3] Baker, D., Childs, B., Durik, M. et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530, 184–189 (2016) doi:10.1038/nature16932

[4] Chang J, Wang Y, Shao L, Laberge R-M, Demaria M, Campisi J, et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med. 2016 Jan;22(1):78–83.

[5] Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, et al. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017 Mar 23;169(1):132-147.e16.

[6] Two-step process leads to cell immortalization and cancer | Research UC Berkeley [Internet]. [cited 2022 Apr 2]. Available from:

[7] Jafri MA, Ansari SA, Alqahtani MH, Shay JW. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med. 2016 Jun 20;8:69.

[8] Schmutz I, Mensenkamp AR, Takai KK, Haadsma M, Spruijt L, de Voer RM, et al. TINF2 is a haploinsufficient tumor suppressor that limits telomere length. White RM, Wellinger RJ, Lingner J, editors. eLife. 2020 Dec 1;9:e61235.

[9] JCI - Long telomeres and cancer risk: the price of cellular immortality [Internet]. [cited 2022 Apr 2]. Available from:

[10] Ungewitter E, Scrable H. Antagonistic pleiotropy and p53. Mech Ageing Dev. 2009 Feb;130(1–2):10–7.

[11] Nelson P, Masel J. Intercellular competition and the inevitability of multicellular aging. Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):12982–7.

[12] Piraino S, Boero F, Aeschbach B, Schmid V. Reversing the Life Cycle: Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula (Cnidaria, Hydrozoa). Biol Bull. 1996 Jun;190(3):302–12.

[13] Why Aging Isn’t Inevitable [Internet]. Nautilus | Science Connected. 2016 [cited 2022 Apr 2]. Available from:

[14] Shorter telomere lengths in patients with severe COVID-19 disease | Aging [Internet]. [cited 2022 Apr 2]. Available from:

[15] Telomere dynamics across the early life course: Findings from a longitudinal study in children - ScienceDirect [Internet]. [cited 2022 Apr 2]. Available from:

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