The telomere code at the end of life: where is the limit of life span?

Produced by: Science Popularization China

Author: Cheng Yiqing, Zhang Peng (High Magnetic Field Science Center, Hefei Institutes of Physical Science, Chinese Academy of Sciences)

Producer: China Science Expo

Editor's note: In order to decode the latest mysteries of life science, the China Science Popularization Frontier Science Project has launched a series of articles called "New Knowledge of Life" to interpret life phenomena and reveal biological mysteries from a unique perspective. Let us delve into the world of life and explore infinite possibilities.

According to historical records, Qin Shi Huang sent alchemists overseas many times to search for elixirs in order to achieve immortality. Emperor Wu of Han was deceived again and again in his pursuit of immortality but remained obsessed with it... It is not difficult to see that throughout the thousands of years of history of Chinese civilization, there has always been an infinite yearning and fanatical pursuit of immortality.

Whether it is the emperors, generals or common people, they all long for a way to achieve immortality. Not only that, the various myths and legends that have been passed down in the world, the various film and television works that have been presented to the public, and even the simple and warm blessings in life such as "live a long life" and "live as long as the Southern Mountains" all reflect the infinite longing of human beings for "immortality".

Birth, aging, illness and death are human nature

(Photo source: veer photo gallery)

However, those who know the ending of the story know that those who pursue immortality will eventually die. As a result, people gradually accepted that birth, aging, illness and death are natural and objective laws, and realized that immortality, which goes against common sense, is just an unrealistic delusion.

The limits of cell division: the end of human lifespan

With the development of the times and the advancement of science and technology, humans have begun to re-observe and examine the world from a scientific perspective. Scientists have begun to explore the inner world of life from the outside to the inside, and have gradually uncovered the mysteries of life. In fact, whether it is aging or death, the "natural occurrence" of these life phenomena can be traced.

In the 1960s, scientists such as Hayflick discovered that there is an upper limit to the number of times a normal human embryonic cell can divide. After a certain number of divisions, the cells will stop dividing and human life will end. Based on this theory, the upper limit of human life span is about 120-150 years.

So why do cells stop dividing? What exactly is limiting human lifespan?

The Clock of Life - Telomeres

We all know that chromosomes are important carriers of genetic information. They can accurately pass genetic information to daughter cells during each cell division. It is precisely because of their existence that each species can maintain its own uniqueness while being passed down from generation to generation, thus achieving "you reap what you sow", allowing all organisms in nature to reproduce in an orderly manner. Therefore, the importance of chromosomes to life is self-evident.

Telomeres

(Photo source: veer photo gallery)

Telomeres are small sections of DNA and protein at the ends of chromosomes in cells, which cover and protect the ends of chromosomes like caps. Telomeres not only protect the integrity of chromosomes, but also control the division cycle of human cells.

Modern molecular biology research has found that every cell division is accompanied by chromosome replication, and every chromosome replication comes at the cost of losing a portion of the end (the telomere). Therefore, as the number of cell divisions increases, the telomeres become shorter and shorter, until they are so short that the cells can no longer divide normally, and the cells will no longer renew, and will only die. Therefore, the mainstream view in the scientific community now is that the length of telomeres indicates the process of cell aging and death, and thus determines the life span of humans.

Aging Process

(Photo source: veer photo gallery)

That is to say, in the absence of trauma and disease, as telomeres gradually shorten, the human body will continue to age until death. Studies have shown that for individuals, the longer the telomeres, the longer they live. Extremely short telomere length is closely related to death caused by hematopoietic malignancies, cardiovascular diseases, digestive and respiratory diseases, drugs, etc. Interestingly, some scientists have found that there are gender differences in the average length of telomeres by comparing male and female T lymphocytes: women's telomeres are longer than men's, and on average they are 8 years "younger" than men.

Comparison of the average telomere length of male and female T cells by two methods

(Image source: Reference [4])

In addition to innate factors that affect the length of telomeres, the acquired environment can also affect it. For example, some scientists have found that psychological stress can also cause telomere damage. It can be seen that maintaining a positive attitude towards life is also very important for health and longevity. So, can telomeres be extended?

Telomere damage caused by psychological stress

(Image source: Reference [2])

Telomerase—the key to longevity?

In fact, as early as 2009, several American scientists discovered telomeres and found a substance in the body that can catalyze the extension of telomeres - telomerase. Telomerase is an RNA-protein complex that uses its own RNA as a template to extend the DNA at the end of chromosomes through the reverse transcription process.

The catalytic core lobe of human telomerase (blue) in complex with histones (pink and brown) and telomeric DNA

(Photo source: veer photo gallery)

In theory, the presence of telomerase can make up for the loss of telomeres caused by cell division, allowing cells to divide indefinitely. However, the telomerase activity in ordinary somatic cells is very low, that is, the speed at which telomerase extends telomeres is far less than the speed at which telomeres are consumed. This is why, although telomerase exists in the human body, it cannot prevent the general trend of telomere shortening in ordinary somatic cells, and cannot make cells immortal.

Although the telomerase activity in ordinary somatic cells is very low, there are some special cells, such as embryonic cells and germ cells, in which the telomerase activity is very high. The telomere DNA in these cells does not shorten with the increase in the number of cell divisions and has the ability to proliferate indefinitely.

So is it possible to activate the telomerase activity in ordinary somatic cells in some way to achieve human immortality?

The choice of life: immortality or death?

In fact, there are some somatic cells in the human body whose telomerase activity suddenly increases, thus achieving unlimited cell proliferation - these are cancer cells. Yes, the cancer cells that terrify humans are immortal. Therefore, if the telomerase activity in ordinary somatic cells is activated, the cells will divide infinitely and further develop into cancer cells. Cancer cells that grow uncontrollably will eventually develop into tumors, resulting in: the cells are immortal, but the person is gone.

Chromosomes with telomeres

(Photo source: veer photo gallery)

From this perspective, the activity of telomerase is restricted in human somatic cells, causing telomeres to shorten during each cell division, which seems to provide a natural mechanism for limiting tumorigenesis and killing cancer cells in the bud.

This shows that the various operating mechanisms in the human body are very precise. The normal shortening of telomeres is a very important part of maintaining human health. They achieve the necessary balance between limiting the life span of cells and the life span of the human body, preventing the occurrence of cancer, and also limiting the life span of life.

At present, it is still unknown whether immortality can be achieved one day in the future, but what is certain is that scientists have been working hard to explore the truth of life. With scientists' deeper research on the human body and the mechanism of telomere shortening and the continuous development of medical technology, the average life expectancy of humans will gradually increase.

References:

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[2] Lin J, Epel E. Stress and telomere shortening: Insights from cellular mechanisms. Ageing Res Rev. 2022 Jan;73:101507.

[3] Ye Q, Apsley AT, Etzel L, Hastings WJ, Kozlosky JT, Walker C, Wolf SE, Shalev I. Telomere length and chronological age across the human lifespan: A systematic review and meta-analysis of

414 study samples including 743,019 individuals. Ageing Res Rev. 2023 Sep;90:102031.

[4] Lansdorp PM. Sex differences in telomere length, lifespan, and embryonic dyskerin levels. Aging Cell. 2022 May;21(5):e13614.

[5] Zhu Y, Liu X, Ding X, Wang F, Geng X. Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondrial dysfunction. Biogerontology. 2019 Feb;20(1):1-16.

[6] Bernardes de Jesus B, Blasco MA. Telomerase at the intersection of cancer and aging. Trends Genet. 2013 Sep;29(9):513-20.

[7] Sandin S, Rhodes D. Telomerase structure. Curr Opin Struct Biol. 2014 Apr;25(100):104-10.