Human Cell and Organism Aging: Are There Limits? Interrupted Case Study on Cell Aging

Human Cell and Organism Aging: Are there Limits? Interrupted Case study on Cell Aging

Teresa Gonya Department of Biological Sciences University of Wisconsin-Fox Valley Menasha, WI

The search for the fountain of youth persists in advertising, and individuals are constantly bombarded with messages about diet, exercise, vitamins and minerals that can help prolong one’s life. The biological basis of aging is often not mentioned in the anti-aging promotions. Is it possible that a diet rich in protein, or fruits and vegetables can add years to your life? Is it possible that a vitamin or mineral ‘tonic’ can promote tissue repair and extend life? Is it possible that a vitamin drink can extend your normal life expectancy? Even clinical medicine focuses on developing new treatments that are based on preventing aging and maintaining organ longevity. We are told to exercise to keep our heart healthy and to stop smoking to prevent damage to body tissues, especially the lungs and blood vessels. The new field of regenerative medicine is based on the premise that stem cells may one day be able to repair tissue and return function to damaged organs.

There are real limits to longevity that are based on genetics, lifestyle, medical history and sociology. (1) At the foundation of organism longevity is cell longevity. All organisms are composed of cells. Four different types of tissue cells form the basis of all organs that are found in any animal organism. Each type of tissue cell has a different ability to undergo mitosis and replace itself, should it become damaged or injured. In general, nerve and muscle tissue have the least potential for cell replacement; connective and epithelial tissue have the greatest potential for cell replacement. Part of this difference is the potential for persistent stem cells to replace damaged tissue. (2) Persistent stem cells are present in most tissues, although many of them (such as nerve cells) are inactivated by potent inhibitors that block mitosis and cell division. (3)

Our understanding of how cells and tissues age is based on the research of many scientists who first studied cell cultures. In the process of investigating methods to obtain good cell culture lines, one group of scientists discovered important information about how long a typical cell lives.(4) Our current ideas of organism aging are based on the early cell culture studies of Leonard Hayflick and Paul Moorhead.

Key Terms to Understand HeLa cells heteroploid diploid karyotype transformation confluent Barr body

© 2007 Teresa Gonya 1 PART 1: Initial insights circa 1950 “So far so good!” Leonard Hayflick was reviewing his notes on the cell lines that had been growing in the culture media for the last month. So far the fibroblast cultures he had begun from the fetal tissues showed no signs of transformation or heteroploidy. This was the 20th cell culture line that he had begun from fetal tissue, and the fibroblasts still resembled the original fetal tissue cells he had isolated. The cultures from liver, kidney and lung were all performing in a similar manner. He reached across the table to turn on the bunsen burner. It was time to transfer the cells to new culture media. Twice each week the cells were transferred and allowed to grow into new sheets of cells on the culture dish. The confluent cell cultures needed careful monitoring to be certain that the cells remained viable. So far, his idea to culture normal human fetal cells had provided consistent results to support his hypothesis that normal cell cultures could be maintained for long periods of time. He currently had cell cultures from different fetuses that were growing in his lab. Similar work with adult human tissue cells had found both normal and tumor cell cultures did not survive indefinitely without changes in chromosome appearance and number.

1. What is the hypothesis that Hayflick is testing?

2. What are the two events that Dr. Hayflick is monitoring to be sure the cultured fetal cells are still identical to the original cells that he isolated from the fetal source?

3. Dr. Hayflick was using fibroblasts from different fetal tissues in his samples. Why do you think that fibroblasts and fetal cells were used in his studies?

4. What did the scientists working on tissue culture hope to accomplish with their work?

(optional) 5. What was the most likely source of the fetal tissues that were used in the Hayflick lab studies?

Dr. Hayflick looked down through the microscope. He blinked and rubbed his eyes to be sure he was seeing the image correctly. Most of the cells had transformed again. His frustration was evident as he stood up and began to pace around the lab. The fibroblasts no longer looked spindle-shaped, and were scattered in loose arrays in the culture dish instead of confluent sheets. Many of the cells were heteroploid, and multiple Barr bodies were visible in cells scattered in the vial. These cultures had been growing for 6 months and most of the cells had replicated between 40 to 45 times before showing signs of cell deterioration. “Cell passage seems to be limited for these cells” he muttered. The damage visible to the cells in culture was similar to the results that other cell scientists had observed. He wondered, "Will the frozen samples be any different?"

When the original cell samples had been isolated from the fetal tissue, Dr. Hayflick had set aside several duplicate cell cultures and frozen them (at -700C). He had thought they would be needed for replicate experiments, and wanted to be sure the cell cultures could be grown again from the same source. Tomorrow he would work with his students to begin new cell cultures from the frozen samples.

1. How did Dr. Hayflick know that the cultures had changed?

2. Why did Dr. Hayflick freeze samples of his initial fetal cells?

3. What can Dr. Hayflick learn from this initial experiment with the fetal cell fibroblast culture?

© 2007 Teresa Gonya 3 Part 3: A different angle The Hayflick lab attempted to establish a strain of permanent fetal fibroblast cultures that maintain their diploid number and form confluent cell sheets like normal cultured cells. Imagine you are a graduate student in his lab, and you are working together with Dr. Hayflick to improve the study. “The initial studies revealed that the cells had a limited life cycle of about 40-45 replications”, remarked Paul. “Is it possible that the cells can’t grow any longer without changing?” “The HeLa cell lines have been established since 1950, and their replication does not seem to be impaired,” contributed Jon. Dr. Hayflick nodded. “Those cell lines are proving that cells can stay in culture for long periods of time. But they are also tumor cells, so that changes their normal cell division response.” “The last culture dish was counted yesterday,” added Lee. “All the cells looked just fine after 35 passages (cell replications). The karyotype appears normal with no signs of heteroploidy. All cells appear normal in appearance, and were covering the culture tray in confluent layers.” “This cell culture had been frozen after 9 replication cycles had occurred,” continued Dr. Hayflick. “and it appears to look normal after 35 additional cycles. So that is a total of 44 cell division cycles it has experienced. It is only a matter of time to see if the frozen cell cultures behave the same as the original samples,” he added. His lab was using a modified protocol to determine just how long cells might stay in a healthy culture environment, and produce cells that are diploid and behave like typical fibroblasts. “Here is the new data we have so far.” Lee distributed the graph of the new results to the lab members. (Figure 1) “Each culture was established and growing for several months before cells were removed and frozen to establish a second cell culture line (B cell group). Subcultures were removed from the B group and frozen at different points in the culture life. Group C had gone through 35 cell division cycles, group D through 30 cycles, group E through 20 cycles and group F through 18 cycles. Each cell culture group had been frozen for various periods of time, in order to determine if the freezing time made any difference in the behavior of the cells.”

Figure 1. History of fetal tissue samples (strain WI-1) Series A represents a continuous cultivation of the cell through 50 passages. Surplus cultures were removed at various passages and stored at -700C. The storage times are indicated by vertical dashed lines with the months of storage shown by the number on the line. The cell cycles (passages) before the cultures were removed and frozen are indicated as well as the length of time the cultures remained viable.(4)

1. What do you think Dr. Hayflick and his students concluded from this data?

© 2007 Teresa Gonya 4 Part 4: A final conclusion? The scientists in Dr. Hayflick's lab concluded that cell cultures could be maintained in culture for 40 to 50 replications whether they were frozen previously or started from a fresh culture. The cell nucleus appeared to experience heteroploidy (different chromosome appearance or number) at a higher rate after 45 divisions, and most became unable to replicate after 50 subcultivations. Lee and Jon walked into the lab meeting beaming with excitement. Both of them were experienced grad students, and had been reviewing the data together. “Here is the collective data for the last few years. It looks pretty interesting!” They passed out a copy of the graph (Figure 2) and everyone crowded around to look at it. Lee had put both the length of time the cells remained in culture and the number of subcultures on the graph and plotted that against the number of cells that had been observed on the culture. “There seem to be three specific phases to the cultured cells,” explained Jon. “Phase I represents the growth of the initial tissue cells in primary (first) culture. Phase II begins with the formation of the first confluent layer of cells. The cells can be maintained in this phase if they are divided and placed into new medium, or subcultured.” “Phase II cells can also transform into tumor cells that have the potential for unlimited growth. According to what Dr. Hayflick has said, those should be called ‘cell lines’ because they can divide indefinitely, like the HeLa cells,” added Lee. “What about the phase III stage?” asked Jon. As a new student, there was still a lot that he did not understand about this research. “Cells that enter Phase III eventually die,” boomed Dr. Hayflick as he entered the lab. “What do you think we can conclude from this data?”

Figure 2. The effects of cell culture on cell transformation and longevity. (4)

1. What conclusions about cells in tissue culture can be drawn from figure 2?

© 2007 Teresa Gonya 5 Part 5: The Hayflick Limit Hayflick’s studies had revealed that fetal fibroblast cultures are limited in both the number of cell replications and the life expectancy. Unlike tumor cells that have an indefinite period of cell replication in culture (they are ‘immortal’), fibroblast cells can only stay in culture for about 50 cell divisions, and survive about 12 months in culture before they transform into tumor cells or undergo cell death. Following the presentation of the summary graph (Figure 2), the grad students wondered: “What happened to the cells to cause them to enter Phase III and eventually die?”

1. List the potential reasons that the cell cultures enter phase III and eventually die.

2. Pick one of these potential causes of cell death, and design an experiment with the cell cultures that could answer the question.

Part 6: Why cells die “The recent work on adult human cells also shows cell division is limited to 40 or fewer cell divisions with a culture life of less than one year”, Hayflick announced at the next lab meeting. “What types of mechanisms could be at work here?” “Could the medium be deficient in nutrients?” asked Jo. “I thought it might be some type of chemical the cell was producing after it entered phase II”, replied Lee. “The cell product might interfere with other cells in the culture and result in a massive transformation that ends with the cells entering phase III and death”. Several other grad students nodded in agreement.

Dr. Hayflick then added his comments to the conversation. “It sounds as if you have narrowed down the possible answers to these two: either something is released from the cells themselves to cause cell death, or something is happening outside the cell in the media to cause cell death”.

Jon continued carefully, “Remember that we cultured both late phase II cell cultures and new fetal cell lines in the same media, and only the late phase II cells went into phase III and died.” He continued, “The new cell lines maintained their potential for replication.” Lee commented, “We also used ‘spent’ culture media from the phase III cells to incubate new initial cell cultures (Phase I) and the cells grew just fine. Doesn’t that mean the culture media itself doesn’t contain any cell-killing material?” “Those are excellent points to consider,” nodded Dr. Hayflick.

1. Hayflick offered two possible explanations for the data that had been observed in the cell culture lines. In your own words, describe these two different explanations.

2. How would you interpret the data mentioned by the last two students?

© 2007 Teresa Gonya 6 Optional reflection: The Hayflick Limit and stem cells The ‘Hayflick Limit’ clearly states that animal cell replication is limited. Each cell can divide approximately 40-50 times. Two different optional discussions that can follow from the cell replication discussion include (1) a discussion of organism aging and (2) stem cell research.

(1) Mechanisms of Organism Aging The Hayflick limit defines human cells’ ability to repair tissues and maintain organ health. We may be able to keep our organs healthy by making good lifestyle choices, but our longevity may still be restricted by our limited ability to produce new cells. Do the limits of a cell’s ability to divide and replace itself diminish our personal efforts to live a long and healthy life? Does the Hayflick limit relieve us of our responsibility to make healthy lifestyle choices? Should we rely on medical innovations to treat diseases of aging, or push for methods to reduce or eliminate environmental toxins that poison cells?

(2) Stem Cell Research and Regenerative Medicine Dolly the cloned sheep suffered from a premature death at age 6 that was 4-6 years earlier than the normal life expectancy of a domestic sheep. The explanation for her death was unclear, but included the presence of aging diseases such as arthritis, and the fact that her DNA source came from an ‘aged’ sample that had already completed many of its predestined cell divisions. (5) Her premature death was thus predicted by the Hayflick limit. Do embryonic or adult stem cells hold more promise in the area of regenerative medicine? If we could determine how stem cells might be grown to replace adult tissues or organs, would this prolong organ function? Would this technology be able to expand our life expectancy?

© 2007 Teresa Gonya 7 Teacher’s Notes Special note: This case study is designed to provide information about the study of cells in culture that gave rise to the discovery of cell replication limits. The study is ‘set up’ and introduced in part #1 and 2 so that students can participate in parts #3, 4, 5, and 6. The active role play of the students reading this case study is important for them to experience how basic ideas are discovered and established as scientific fact. This case is based on a few assumptions that may be inaccurate. Leonard Hayflick and Paul Moorhead received complete credit for this work, and my use of students as key players should not be interpreted as an attempt to detract from their remarkable work. The conversations between Dr. Hayflick and his “graduate students” are complete fabrications in order to draw the students using this case into the conversation about how scientific inquiry really happens.

Leonard Hayflick is best known for his discovery of mortality in human cell cultures, or the “Hayflick Limit”. Until his classic study on human cell cultures, most scientists thought that human cells were ‘immortal’ and could divide without limit. This was true for tumor cells, which exhibit heteroploidy after many cell divisions. Hayflick was able to develop the first diploid human cell culture, that maintained normal cell appearance for approximately 50 cell divisions before transforming appearance or chromosome structure (heteroploidy). The concept of telomers capping the ends of DNA molecules, and limiting cell division provided a potential mechanism for the ‘Hayflick Limit’. A.G. Bodner’s work on telomerase showed that telomer growth acted to prevent cell death, and this supported the idea that telomers were the mechanism behind the Hayflick limit. (7)

Hayflick began his work to show that human cell cultures could be used to produce virus vaccines. At the time of his studies, it was thought that cell cultures were immortal (could divide indefinitely), primarily because most cultures were made from tumor cells that have this ability. However, most tumor cells also change in cell and chromosome appearance. In the 1950’s viruses were also suspected of causing cancer, so the general understanding that cancer cells were immortal and (perhaps) caused by viral infection limited the use of mammalian cell cultures to form viral vaccines. He devised the cell freezing and sub-culture procedure to keep his diploid cell line alive once he realized that the diploid cell replication cycles were limited to 50 cycles. This discovery alone formed the foundation for current research in cell and organism aging.

The ‘Hayflick Limit’ overturned the dogma of continuous cell replication, and also established that normal mammalian cells were mortal and cancer cells were not. After Hayflick realized the limitations of the diploid cell cultures, he was able to successfully adapt the cell culture technique for viral vaccine production. One specific cell strain was first used for the production of the oral polio vaccine, and it also has been used to develop vaccines for rubella, rubeola, rabies, and adenoviruses as well as regular poliomyelitis vaccines. Hayflick also developed a specialized culture media to isolate and identify the agent that causes ‘walking’ pneumonia, or Mycoplasma pneumoniae. (6) Since the 1980s, Hayflick has spent much of his time analyzing the overall state of aging research, even publishing a popular book on the subject, “How and Why We Age” in 1994. He is interested in current research in stem cells, which offers the potential to replace damaged tissues and organs, and also feels that the focus of current aging research should focus more on the cell rather than diseases of aging. (8) Stem cells may actually

© 2007 Teresa Gonya 8 offer one route to learn about cell aging, and perhaps discover ways to make ‘old’ cells more resistant to disease than younger ones. Hayflick believes that this approach probably will not lengthen lifespan, but it could improve quality of life as we age.

Bibliography

1. Suzzette Chopin, Biological Basis of Aging. HAPS update Seminar, May 28, 2007. 2. Stem cell research reveals culprit in aging muscles that heal poorly. http://www.medicalnewstoday.com/articles/79373.php 3. Adult stem/progenitor cells repair of damaged brain, pancreas, kidney cells newly understood. http://www.medicalnewstoday.com/articles/69354.php 4. Hayflick, L and Moorhead, P.S., The serial cultivation of human diploid cell strains. (1961). Experimental Cell Research (25) 585-621. 5. Dolly the Cloned Sheep, biography http://www.answers.com/topic/dolly-the- sheep?cat=technology 6. Hayflick Biography http://www.agelessanimals.org/hayflickbio.htm 7. Bodner, A. G. et al. (1998) Extension of lifespan by introduction of telomerase into normal human cells. Science (279) 5329. 349-352. 8. American Federation for Aging. http://www.infoaging.org

Part #1 1. What is the hypothesis that Hayflick is testing? Hayflick was trying to develop an immortal cell line from the fetal cells. His general hypothesis was that fetal stem cells can be cultured in vitro for unlimited amounts of time if the culture conditions can be determined.

2. What are the two events that Dr. Hayflick is monitoring to be sure the cultured fetal cells are still identical to the original cells that he isolated from the fetal source? Transformation and heteroploidy

Dr. Hayflick was looking for transformation of cells that would indicate that the cells had changed in appearance, and no longer looked like fibroblasts. Changes in chromosome form (heteroploidy) also indicate that cultured cells are no longer in the same state as initial cells. During the early days of cell culture, long-term success of persistent cell cultures was dismal. Usually cells transformed (changed) into cancer-type cells that persisted indefinitely, but no longer resembled the original cells in appearance or function.

3. Dr. Hayflick was using fibroblasts from different fetal tissues in his samples. Why do you think that fibroblasts and fetal cells were used in his studies? Fetal cells were a new cell source that could be kept in constant culture by freezing. One of the reasons to use fibroblasts was an attempt to control variables that might influence the culture lines. All the original cell cultures used fibroblasts. They are also the most common type of cell in tissue cultures, and they could be harvested from all fetal organs. Previous work with adult cells had been unsuccessful in maintaining a cell culture that did not transform into altered cells.

4. What did the scientists working on tissue culture hope to accomplish with their work? Establishing cell cultures that could be maintained outside the body would provide a cell source to experiment with new medications for cancer treatment, isolate causes of cell disorder, study effects of environmental changes on cell behavior, study how different cells work, how tissues form, how tissues could be repaired, help new medications /treatments for disease be developed. One of the In discussion, this conversation can be applied to the use of stem cells in ongoing research in development and regenerative medicine.

(optional) 5. What was the most likely source of the fetal tissues that were used in the Hayflick lab studies?

Since this work was done in the 1950’s and abortion was not a legal operation, most of these tissues were obtained from stillbirths or premature deliveries. Although this may not be a biological point, the issue of ethics could be discussed using this point. Ethical considerations in the 1950’s were completely different than they are now, as were the regulations governing human research. Research that requires human tissue or human

© 2007 Teresa Gonya 10 subjects must now meet strict requirements for no harm to the donor or research subjects. If the same study were done today, the use of fetal tissue would require strict standards to assure that all tissue was obtained with permission from the maternal source, and all ethical concerns were addressed. The legalization of abortion did not provide an open opportunity for more fetal cell sources, as sometimes suggested by the political agenda of stem cell research opponents.

Part #2 1. How did Dr. Hayflick know that the cultures had changed? Cells appeared to have changed their behavior with other cells, and the chromosome shapes were different (heteroploid). Cell appearance, and the appearance of the culture cells in clumps, not in sheets, indicated that the cells were no longer holding together as they should. This is one of the indications that the cells had transformed.

2. Why did Dr. Hayflick freeze samples of his initial fetal cells? One reason that cells were removed from the original tissue source was to maintain a cell source so that his studies could be repeated again. This is the best way to avoid drawing conclusions from one source and one sample.

3. What can Dr. Hayflick learn from this initial experiment with the fetal cell fibroblast culture? There may be many ideas that the students will generate. One is that cell life may be limited. Another that cells cannot be maintained in culture indefinitely without changing.

4. There are new factors that need to be considered in the design of the second experiment that were not present in the first set of studies. How should Dr. Hayflick test his hypothesis with the frozen cells? The Hayflick lab is trying to determine if human cell cultures can be established and maintained without transformation from fetal sources. Because the lab has spare cells in the freezer from each fetal tissue sample, they still have tissue to work with. This “trouble-shooting” exercise may be difficult for many introductory students. They should recognize that the frozen cells may be different from the original cells because they have been frozen. Their experimental design should include this new variable. The basic idea that cell constancy in ploidy and appearance are the end measurements of the cell culture are important to focus on. The scientists were using heteroploidy, cell appearance, and the behavior of the cell culture (to form confluent cell sheets) to determine if the cells were still behaving the same in culture as they were in the original tissue.

Part #3 1. What do you think Dr. Hayflick and his students concluded from this data? Most of the cell cultures had the ability to replicate no more than 50 times before they showed signs of cell heterotrophy, abnormal cell adhesion, and eventual cell destruction. If a cell sample had been frozen and re-cultured then the re-established culture had a total replication cycle of 40-50 cycles.

© 2007 Teresa Gonya 11 Part #4 1. What conclusions about cells in tissue culture can be drawn from figure 2? Cells grown in tissue culture have a known limit to reproduction cycles and cell life. At the time of the study, fetal cells could be maintained for up to one year in culture, and they had a maximum of 50 cell divisions before they experienced transformation and/or death.

Part #5 1. List the potential reasons that the cell cultures enter phase III and eventually die. Students might list: accumulation of some metabolite that causes cell injury; the production of an aging factor that causes cell injury; the loss of a factor that normally removes metabolites from the cell; production of a virus particle that damages the cell and other cells in the culture; old cells lose the ability to repair themselves; old cells accumulate cell damage from the environment; genes in cell stop working; some growth factor present in the early cells becomes too dilute in the cell after 50 cell divisions and the cell dies from lack of its growth factor. This process may generate many ideas that were not available to Hayflick in the 1950s, such as telomeres, aging genes, oxygen radical damage, protein glycosylation, etc.

2. Pick one of these potential causes of cell death, and design an experiment with the cell cultures that could answer the question. Answers will vary based on the students’ responses. After students do generate ideas to question #1, then you could pick one idea that most people think is a ‘good’ one and design an experiment as a group (if your class is small). Or students can work in group.

Part #6 1. Hayflick offered two possible explanations for the data that had been observed in the cell culture lines. In your own words, describe these two different explanations. Students should be able to restate the idea that cell aging occurs in culture as an effect of some chemical change within the cells themselves, or some physical change to the environment surrounding the cell. These would be Hayflick’s ‘internal’ or ‘external’ influences that he describes in the summary of his 1961 paper.

2. How would you interpret the data mentioned by the last two students? The data clearly rule out the possibility that a chemical found in the medium or produced by the cell and added to the medium is causing the cell death reported in the cultures in Phase III cultures. The used media did not kill new cells incubated in it, and the same media used to incubate dying phase III cells did not kill phase I cells that were added to the culture. Hayflick's summary includes the following statement:” A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level.“ (4).

Optional Reflections (1) Mechanisms of Organism Aging The Hayflick limit defines human cells’ ability to repair tissues and maintain organ health. We may be able to keep our organs healthy by making good lifestyle choices, but our longevity may still be restricted by our limited ability to produce new cells. Do the limits of a cell’s ability to divide and replace itself diminish our personal efforts to live a long and healthy life? Does the Hayflick limit relieve us of our responsibility to make healthy lifestyle choices? Should we rely on medical innovations to treat diseases of aging, or push for methods to reduce or eliminate environmental toxins that poison cells? Mechanisms of organism aging can be discussed with the limit in mind. The Hayflick limit defines our cells ability to repair tissues and maintain organ health. We may be able to keep our organs healthy by making good lifestyle choices, but our longevity may still be restricted by our limited ability to produce new cells. Students could reflect on the role of their responsibility to maintain good lifestyle choices balanced against the limited ability that medicine provides to treat diseases that occur (or “fix” organism aging). Students could research the role of genes, free radicals, social networking, and spirituality on life expectancy and longevity. Resources: The National Institute on Aging (http://www.grc.nia.nih.gov) Baltimore Longitudinal Study of Aging (http://www.grc.nia.nih.gov/branches/blsa/blsafindings.pdf )

(2) Stem Cell Research and Renerative medicine Dolly the cloned sheep suffered from a premature death at age 6 that was 4-6 years earlier than the normal life expectancy of a domestic sheep. The explanation for her death was unclear, but included the presence of aging diseases such as arthritis, and the fact that her DNA source came from an ‘aged’ sample that had already completed many of its predestined cell divisions. (5) Her premature death was thus predicted by the Hayflick limit. Do embryonic or adult stem cells hold more promise in the area of regenerative medicine? If we could determine how stem cells might be grown to replace adult tissues or organs, would this prolong organ function? Would this technology be able to expand our life expectancy?

Students could reflect on the use of embryonic versus adult cells in regenerative medicine research. The limits of adult stem cells include their previous cell replications and their specialization. Embryonic stem cells have a longer cell replication potential and they are undifferentiated. Using the Hayflick limit as a focus of discussion, students could analyze the biological use of one stem cell over the other in regenerative medicine. Many scientists who work in the stem cells feel that the real beauty of embryonic cells is their ability to provide clues about tissue differentiation and aging. Stem cell research might allow scientists to design ways to discover how cells age, and why diseases alter old cells more than they alter young ones.