Life Extension Magazine®

Issue: Nov 2014

The 2014 Genetics of Aging And Longevity Conference Held in Sochi Russia

Topics covered at this year’s Genetics of Aging and Longevity Conference included a new cryoprotectant that preserves transplant organs, the creation of artificial organs from stem cells, and the development of artificial human chromosomes to correct genetic defects.

By Ben Best, BS, Pharmacy.

Enhance Endothelial Health How Pomegranate Protects Against Atherosclerosis  

The 2014 Genetics of Aging and Longevity conference was held in Sochi, Russia, shortly after the 2014 Winter Olympics had been held in that city. The conference attracted many of the world’s leading researchers whose work is devoted to fighting the disease known as aging.

Inflammaging

Franceschi
Franceschi

Claudio Franceschi, MD, (Professor, University of Bologna, Bologna, Italy) is noteworthy in aging research for promoting the inflammation theory of aging―and for coining the term “inflammaging.” Acute inflammation can repair injured tissues and eliminate attacking microorganisms. But aging is too often characterized by chronic inflammation that is damaging rather than beneficial.

In his presentation, Dr. Franceschi provided evidence for the use of inflammation symptoms as a means of determining biological age, as distinct from chronological age: a biomarker of aging. A biomarker of aging would be useful for determining if drugs or other interventions intended to slow aging are effective.1

Dr. Franceschi has conducted many studies on people of many ages, but particularly has studied people who have lived extremely long lives. He and others have found that glycosylation (linkage of sugars to proteins) is a biomarker of aging that contributes to inflammation.1-3 Other biomarkers of aging that he has found are epigenetic changes (certain changes in gene expression)4 and changes in amino acids and blood lipids.5,6

Frailty Index

Mitnitski
Mitnitski

Arnold Mitnitski, PhD, (Professor, Dalhousie University, Halifax, Canada) has spent much of his career seeking to study and validate a quantitative measure similar to biological age: a frailty index. A high frailty index would indicate a high probability of increasing health problems and a high probability of becoming institutionalized.8

Although people are living longer, their health span has not increased to the same extent. In Europe, men spend about one-fifth and women spend about one-quarter of their lives in a state of disability.9 In the United States, 95% of Medicare costs are spent treating persons with two or more chronic diseases.10

Dr. Mitnitski’s frailty index is a quantified composite of scores related to strength, mobility, cognition, nutrition, sleep, emotion, etc.11 He found that the first activities of daily living to become impaired with increasing frailty are bathing, cooking, and managing medication.12 He also found that for any frailty index value, the mortality rate among men is higher than the mortality rate among women.11 Women tolerate stress resulting from health deficits better than men. Long-lived males are those who do not accumulate health deficits.13

Low Temperature Organ Preservation

Fahy
Fahy

Gregory Fahy, PhD, (Vice President and Chief Scientific Officer, 21st Century Medicine, Fontana, California) is one of the world’s leading authorities on preserving organs at extremely low temperatures. Many people who are otherwise healthy die because of the failure of a single bodily organ—most often the heart, lung, kidney, or liver. Dr. Fahy believes that replacement of failed cells, tissues, or organs could cause over 30% of all deaths in the United States to be substantially postponed—increasing the chance of living to age 90 by more than 10 times.14

Unfortunately, the supply of transplantable organs is much less than the demand. There are long waiting lists of potential organ transplant recipients, most of whom die before an organ becomes available. In the United States, it estimated that only about 2% of the potentially needed organ transplants are carried-out.14 Even when organs are transplanted, they may be poorly matched to the recipient, requiring immune suppression measures that decrease the quality and quantity of life of the recipient.15

Dr. Fahy mentioned progress in tissue engineering, which should result in creation of organs from recipient stem cells.16 This would eliminate problems with immune system compatibility. Transplantable organs are highly perishable—having a four- to 48-hour storage limit.17

Many organs deteriorate too much before they can be used. Dr. Fahy’s work is devoted to developing means to preserve transplantable organs for decades (if not centuries) by cooling to extremely low temperatures.

Freezing normally occurs when tissues or organs become too cold, but since 1984, Dr. Fahy has pioneered the use of cryoprotectant (medical-grade antifreeze) solutions that result in vitrification (glass) rather than freezing (ice).18 His first success was vitrification of mouse embryos.19 Unfortunately, many cryoprotectants are too toxic to be of use for preserving animal tissues or organs.20

After nearly 20 years of research, Dr. Fahy and his colleagues were able to develop a vitrifying cryoprotectant solution that is nontoxic enough for preserving large organs.21 Using his new cryoprotectant solution, Dr. Fahy’s team was able to able to cool a rabbit kidney to -130°C (-200°F), rewarm the kidney, and transplant the kidney back into the rabbit such that the rabbit was able to survive with only the rewarmed kidney.22 The kidney was not completely undamaged, however. Blood flow rates in the inner part of the kidney are much less than in the outer part, which means there will be much less saturation of vitrifying cryoprotectant into the tissue of the inner kidney when the kidney is perfused. Also, ice can form more readily on rewarming than upon cooling.23 Dr. Fahy described methods he and his team have developed to overcome these problems, such that he is hopeful that they can demonstrate more successful cryopreservation of kidneys in the near future. The Life Extension Foundation® has funded much of Dr. Fahy’s research.

Organs From Stem Cells

Soker
Soker

Shay Soker, PhD, (Professor, Wake Forest School of Medicine, Winston-Salem, North Carolina) is attempting to create transplantable artificial organs from stem cells. Creating a scaffold for the stem cells is much less difficult than creating a network of blood vessels within the scaffold. He has nonetheless had some preliminary success in experiments with animal livers.24,25

About one-fifth of human kidneys obtained for transplant become unusable and are disposed of. 26 Dr. Soker has experimented with removing cells from pig kidneys to create a scaffold for stem cells. The pig kidneys from which he had removed the pig cells retained functional blood vessels. He hopes that this procedure can be applied to discarded human kidneys because his process removes antigens, thereby reducing problems of immune system incompatibility that usually accompanies transplantation.26 Because of the immune system suppressant drugs that kidney transplant recipients must take, those patients are vulnerable to infection, and 40% of those who took the immune system suppressants for 20 years developed cancer.27

Stem cells in bone marrow  

Dr. Soker has also removed cells from pig pancreases to obtain a pancreas scaffold that can be used for seeding with stem cells. He is hopeful that similar decellularized pig pancreases could be transplanted into human diabetes patients.28 In addition, Dr. Soker has been working to develop a completely artificial cornea—having a scaffold of gelatin, which would eliminate the need to obtain corneas from humancadavers.29

Asymmetric Cell Division

Mikolaj Ogrodnik (Graduate student, Newcastle University, United Kingdom) has been studying asymmetric cell division (where cells divide without both sides being the same) as a means of rejuvenation. Single-celled organisms like yeast and bacteria can rejuvenate when damaged proteins go into one of the new cells created by cell division, allowing the other cell to be rejuvenated.30 More recently it has been shown that stem cells in fruit flies are rejuvenated by a similar method.31 Ogrodnik was able to determine that this also occurs in mammalian cells.32 Gaining control of this process could facilitate tissue rejuvenation in humans.

Molecular Mechanisms Of Hormesis

Moskalev
Moskalev

Alexey Moskalev, DSc, (Professor, Syktyvkar State University, Syktyvkar, Russia) was one of the conference organizers. His research has been focused on studying the molecular basis of hormesis: The fact that a small amount of stress can lead to greater resistance to stress in the future.33 For example, a person who undergoes the stress of exercise becomes more generally resistant to harmful effects of many forms of stress.34

Dr. Moskalev has shown that low-dose radiation produces a hormesis effect in fruit flies. He has studied the molecular basis of this hormesis, which includes induction of heat shock proteins and improved DNA repair.35 He believes that a stress-induced hormesis response can result in changes in the way genes are expressed, leading to improved likelihood of longevity.36

Databases And Computation For Aging Research

de Magalhães
de Magalhães

Joao Pedro de Magalhães, PhD, (Senior Lecturer/Associate Professor, University of Liverpool, Liverpool, United Kingdom) is a leading proponent of the use of massive amounts of data and computational resources to understand and prevent aging.37,38 He described the Human Ageing Genome Resources website (www.genomics.senescence.info) he and his colleagues created, which is a collection of databases and other resources to assist those researching aging. GenAge is a database of genes related to aging; AnAge is a database of other data related to aging from thousands of species; GenDR is a database of genes associated with calorie restriction; and LongevityMap is a database of human genetic variants associated with longevity.39,40

Dr. de Magalhães has also created a website called www.senescence.info, which has a wide variety of information related to aging, including suggested books and book reviews, advice to students regarding aging research, a Who’s Who in gerontology, an anti-aging medicine page, and much more.

Dr. de Magalhães not only collects data, he analyzes it. In one study, he found 56 genes that become increasingly expressed with age, and 17 genes that are decreasingly expressed.41 He believes that many of the genes that are increasingly expressed with age are an adaptation to aging deficits rather than a cause of aging—such as genes that produce enzymes to degrade the increasing number of malformed proteins that accumulate with age.41 On the other hand, genes that are less expressed with age are more likely to actually cause aging—such as genes that produce components of the energy-producing mitochondria of cells.41

Dr. de Magalhães received a grant from the Life Extension Foundation® that enabled him to sequence the genome of the bowhead whale. The bowhead whale is the longest-living mammal, having a life span of 200 years or more.42

Human Artificial Chromosomes

Yuryeva
Yuryeva

Ksenia Yuryeva, MD, (Research Fellow, Human Stem Cells Institute, Moscow, Russia) has been working on the development of human artificial chromosomes as a means of gene therapy. Gene therapy attempts to correct diseases due to inherited genetic defects.

Gene therapy most often uses viruses to transport desired genes into the cell nucleus of the subject being treated. There are two problems with this approach. First, viruses are unable to carry very much genetic material due to their small size.43,44 Second, using a virus to transport a gene into the DNA of the subject’s chromosomes reduces control over where in the target chromosome the gene would be inserted. Insertion in the wrong location could cause cancer or have other undesirable consequences.43

The use of human artificial chromosomes overcomes both of these problems by providing a new chromosome in addition to the ones that already exist in the cells of the subject. Dr. Yuryeva reported on the use of artificial human chromosomes to deliver large genes to correct muscular dystrophy in mice that have the disease due to genetic defects.45 Human artificial chromosomes have also been used to create induced pluripotent stem cells.46,47 The development of human artificial chromosomes creates the possibility of easily delivering to everyone many beneficial genes that could greatly increase health and longevity.

Roundtable Discussions

In addition to the formal presentations, this conference also held roundtable discussions. This was literally a round table of about 30 participants, with an additional 20 or more participants sitting to the side. I will attempt to summarize some of the comments made in these discussions without identifying individual commentators.

Theories Of Aging

Not surprisingly, there was much discussion about theories of aging. Aging in animals isn’t simply a matter of wear-and-tear as with an automobile. Animals, unlike cars, have built-in repair mechanisms, such as DNA repair enzymes or the ability to degrade defective proteins. Aging is as much a matter of defective repair as of wear-and-tear.

One researcher suggested that aging isn’t only a loss of function, it is a loss of control, such that some functions become excessive. The chronic inflammation of old age is an example of a beneficial biological response that has gone out of control. Another researcher said that chronic inflammation is due to an increase in garbage in cells and tissues. The inflammatory response to the garbage results in the creation of even more garbage.

Another researcher noted that aging is drying because babies are soft and wet, whereas the elderly are hard and dry. Someone else commented that aging is unpleasant and unattractive, and that anyone claiming otherwise is just attempting to rationalize out of despair. Someone else said that chronic diseases drive the aging process as much as aging results in chronic diseases.

Personalized Medicine

Personalized Medicine  

There was also a roundtable on personalized medicine. The phrase “personalized medicine” has recently come to mean genomic information to diagnose and treat patients, as well as to assess probable future risks of disease.48 A physician complained that geneticists have hijacked the phrase “personalized medicine” because for him treating his patients has always been a very personal matter. A researcher said that personalized medicine should include not just genetic information, but blood tests along with signs and symptoms.

There was a discussion of the November 2013 letter from the Food and Drug Administration (FDA) to 23andMe (23andMe.com) telling that company to stop marketing their product until receiving FDA approval to do so. 23andMe was providing genetic and health information on the basis of DNA analysis of saliva samples.49 Someone said that the FDA’s action is contrary to the “My Body, My Rights” campaign by Amnesty International, which states everyone has a right to unrestricted access to information regarding their own health. On this basis, governmental and medical paternalism is interfering with those rights.

The FDA’s position is that the 23andMe tests had not been adequately validated, and that the FDA must protect consumers from misinformation that could damage their health.49 There was also concern that consumers might misuse information they were receiving in the absence of professional help with medical decisions.50 Questions were raised about what people should and should not be told, but no agreement was reached.

“Quantified Self-Improvement” was mentioned in reference to the growing number of health-monitoring devices on the market that are providing increasing amounts of personal health and activity data to consumers, as well as in reference to the fact that there is no stopping consumers from attempting self-diagnosis and treatment on the basis of information they find on the Internet.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

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