Life Extension Magazine®

Vials being used to repeat studies from Biogerontology Conference

European Biogerontology Conference In Beer-Sheva, Israel

At the European Congress on Biogerontology, an international group of scientists presented cutting-edge research on aging, including findings on longevity epigenetics, rejuvenation of the immune system, the dangers of CMV infection, and calorie restriction.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in August 2023. Written by: Ben Best, BS, Pharmacy.

European Biogerontology Conference In Beer-Sheva, Israel 

As you may know, I was hired by the Life Extension Foundation® to attend worldwide scientific conferences and report findings from these events to you in this magazine. I typically attend about two conferences a month. An advantage of attending these conferences is that new information is often presented long before it gets published in a journal.

Some conferences I attend yield little in the way of apparent advances in our understandings of aging. This year’s European Congress on Biogerontology held in Israel, was exceptional in the volume of meaningful research findings that were disseminated. What follows is my succinct report.

Why Naked Mole Rats Don’t Get Cancer


Vera Gorbunova, PhD (Professor, University of Rochester, Rochester, New York) reported on the investigations she and her husband (Andrei Seluanov, PhD) have made into why naked mole rats live so long and don’t get cancer. Her husband has the second largest naked mole rat colony in the world. Naked mole rats are about the same size as mice, but live about ten times longer.

Cancer is the cause of death in nearly all laboratory mice that die naturally, but cancer has never been observed in a naked mole rat. Normal cells are limited in the number of times they can divide, but cancer cells often have the enzyme telomerase, which allows them to divide an unlimited number of times. The abundance of telomerase in mouse cells is believed to be one of the reasons mice so often die of cancer. But Dr. Seluanov and Dr. Gorbunova have found that naked mole rats have about as much telomerase as mice.1 So the naked mole rats must be preventing cancer by some other means.

Why Naked Mole Rats Don’t Get Cancer  

The two scientists found that naked mole rat cells stop growing when the cells start to crowd each other.2 Cancer is the uncontrolled growth of cells, which can quickly lead to a crowding of cells - something that the biology of naked mole rats prevents. Dr. Gorbunova reported that she and her husband later discovered that naked mole rats secrete a form of hyaluronic acid that is five times larger than what human or mouse cells secrete. When the hyaluronic acid was removed from the naked mole rat cells, they became as vulnerable to cancer as mouse cells.3 That discovery was reported in the July 18, 2013 issue of the journal Nature as a cover story.

Thanks to funding from the Life Extension Foundation®, the husband and wife team then discovered that naked mole rat protein synthesis produces remarkably few errors.4 Both of those discoveries caused the journal Science to name the naked mole rat the 2013 “Vertebrate of the Year.”5

As described in the January 2014 issue of Life Extension Magazine®, Dr. Seluanov was denied funding by the federal government because the genome of the naked mole rat is known. Without Life Extension Foundation® financial support, he was in danger of losing his naked mole rat colony entirely.

Calorie Restriction In Monkeys


George Roth, PhD (CEO, GeroScience, Inc, Pylesville, Maryland) discussed the seemingly conflicting results of calorie restriction studies on rhesus monkeys being conducted at the National Institute on Aging (NIA) and the University of Wisconsin (UW).

Dr. Roth was affiliated with the NIA study. Life span studies on rodents and more short-lived species have shown that calorie restriction with adequate nutrition extends both average and maximum life span.6 The relevance of these studies to humans is disputed on the grounds that such a mechanism would only be needed by short-lived species for survival.7

Unlike rodents, which do not generally develop diabetes or cardiovascular disease with age, humans and rhesus monkeys have a similar pattern of aging-associated diseases. Life span studies on humans are not typically feasible because of the long time involved, but rhesus monkeys also live quite long: an average of 27 years and maximum of 40 years when in captivity.

The NIA and UW monkey studies began over 30 years ago, but those life span studies will not be concluded until all the monkeys have died, which will take at least another 10 years. Nonetheless, both institutions have released preliminary results.

UW results released in 2009 indicated that only 13% of the calorie-restricted monkeys had died of age-related causes compared with 37% of the controls (who were not calorie-restricted).8 The calorie-restricted monkeys had half the incidence of cancer and cardiovascular disease―and no cases of diabetes. Nearly an eighth of the control monkeys had developed diabetes. This UW study showed robust survival improvements in calorie-restricted monkeys along with huge reductions in incidences of the diseases that most commonly strike aging humans.

Calorie Restriction In Monkeys  

Preliminary results released from the NIA study in 2012 reported that 20% of the calorie-restricted monkeys had died of age-related causes, compared with 24% of the controls―which is not a statistically significant difference.9 One explanation for the conflicting results may be that the UW control monkeys could eat whenever they wanted (which represents the typical human diet), whereas the NIA control monkeys received a standard allotment of food, which mildly restricted their calories. On average, there was a greater difference in body weight between the calorie-restricted and the control monkeys at UW than at the NIA. In rats, very low levels of dietary restriction have a significant effect on survival,10 so the NIA controls may be showing those benefits, which diminished the longevity difference between the two groups of monkeys (calorie restricted versus controls).

Although both the NIA and the UW monkeys received nearly 60% carbohydrates, the UW diet was 28.5% sucrose, whereas the NIA diet was only 3.9% sucrose.9 The UW protein source was lactalbumin, whereas the NIA diet included fish meal, which is rich in omega-3 fatty acids.9 Omega-3 fats are known to reduce cardiovascular disease.11,12 Differences in diet composition could explain the differing results between these two studies.

The media used the NIA study to question the value of humans reducing their calorie intake, which is regrettable as the UW study demonstrated remarkable survival improvements. The beneficial changes that occur in calorie-restricted humans (such as reduced blood levels of glucose, insulin, lipids and inflammatory markers, and lower body weight) clearly show this is what humans should be doing, yet misleading media headlines made it appear that it is alright for people to calorically overindulge.

Dr. Roth acknowledged that he does not have the self-discipline or inclination to practice calorie-restriction. For this reason he has long been looking for supplements that produce the benefits of calorie restriction.13 He noted that the Wikipedia entry on “caloric restriction mimetic” lists resveratrol, metformin, and other compounds that are claimed to produce the benefits of calorie-restriction.

Longevity Genes And Longevity Epigenetics


Nir Barzilai, MD (Director, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York) is interested in genetic and lifestyle causes of longevity. He has determined that although a healthy lifestyle may promote longevity in the general population, protective genes are more important than lifestyle for achieving extreme longevity.14 Studying Ashkenazi Jews aged 95 or older, he has found some highly protective genes. One such gene encodes a plasma protein that transfers cholesterol and triglycerides between the various forms of cholesterol carriers (HDL, LDL, and VLDL). 15,16 Another longevity gene, which encodes a cholesterol carrier, harbors a modification that occurs in about 10% of individuals aged 60, but in about 25% of centenarians (people over 100 years of age).17


Gil Atzmon, PhD (Associate Professor, Albert Einstein College of Medicine, Bronx, New York), who is a collaborator of Dr. Barzilai, is interested in the epigenetics of longevity. Epigenetics is the heritable modification of gene expression that is not controlled by DNA sequence. Comparing the children of centenarians with their spouses, Dr. Atzmon determined that the children had half the incidence of diabetes, a 60% lower incidence of heart attacks,18 and higher levels of protective cholesterol (HDL cholesterol).19 Dr. Atzmon has also determined that centenarians have had fewer children, and reproduced later in life than the general population.20 Although identical twins have the same genome (DNA sequences), their epigenetic differences increase with age, particularly when their lifestyles differ and they have not spent much time together. 21 A greater randomness of epigenetic changes, such as methylation patterns, are associated with the “biological aging rate.”22 Dr. Atzmon has identified specific epigenetic changes associated with longevity.

European Biogerontology Conference Held In Israel

On March 10-13, 2013 the 8th European Congress on Biogerontology was held in Beer-Sheva, Israel. Israel has a special partnership status with the European Union. By being held in Israel, the conference was attended by a large number of American scientists who originated from Israel or were educated in Israel.

Beneficial Mitochondrial Peptide


Pinchas Cohen, MD (Dean, School of Gerontology, University of Southern California Davis, Los Angeles, California) is an expert in humanin, a protein (peptide) produced in mitochondria. Mitochondria are energy-generating organelles in cells, which have their own DNA separate from the DNA in the nucleus.23 The amount of DNA found in the mitochondria is much less than that found in the nucleus. As such, mitochondrial DNA contains codes for only a few proteins, humanin being one of them. Humanin was discovered by a search for factors helping to keep neurons alive in undiseased portions of the brains of Alzheimer’s disease patients.24 Humanin protects neurons against cell death in Alzheimer’s disease, as well as protecting against toxic chemicals and prions (toxic proteins).25 Dr. Cohen’s team has shown that humanin also protects cells lining blood vessel walls, preventing atherosclerosis. In particular, they have shown that low levels of humanin in the bloodstream are associated with endothelial dysfunction of the coronary arteries (arteries of the heart).26 Humanin has also been shown to promote insulin sensitivity, the responsiveness of tissues to insulin. 25 Because humanin levels decline with age, it is believed that reduced humanin contributes to the development of aging-associated diseases, including Alzheimer’s disease and type II diabetes.25

Muscle Stem Cells And Aging

Zipora Yablonka-Reuveni, PhD (Professor, University of Washington, Seattle, Washington) has been studying muscle stem cells. Injury, exercise, and even routine daily activity results in muscle damage that is repaired by muscle stem cells. Age-related muscle deterioration is associated with a substantial decline in skeletal muscle mass, strength, and quality,27 which contributes to frailty in the elderly. Dr. Yablonka-Reuveni has established that the quantity of muscle stem cells declines with age, but the regenerative potential of those stem cells does not decline.28 Using running rats she demonstrated that exercise results in an increase in subsequent spontaneous activity in the old rats.

Immune System Stem Cells In Aging And Diabetes

Paolo Madeddu, MD (Professor, University of Bristol, Bristol, England) is concerned with the effects of aging and diabetes on the immune system. Influenza vaccine is less effective in the elderly.29 A decline in stem cell function in the immune system is believed to be partially responsible for this effect.30 Stem cells of the immune system are created in the bone marrow. Dr. Madeddu’s team has established that immune system stem cells of diabetic patients are damaged as a result of blood vessel malfunction in the bone marrow.31,32 His team has shown that insulin replacement significantly protects bone marrow blood vessels.33


Eliminating Senescent Cells

Adi Sagiv, PhD student (Weizmann Institute of Science, Rehovot, Israel) has been studying fibrosis in the liver, which is caused by senescent cells (aged cells). Fibrosis is limited when immune system cells known as natural killer cells (NK cells) kill the senescent cells.34 Dr. Sagiv has been investigating means by which NK cells can be activated to enhance the elimination of senescent cells, and thereby reduce fibrosis.35

Stem Cells From Fat For Heart Attack


Jonathan Leor, MD (Professor of Cardiology, Tel-Aviv University, Tel Aviv, Israel) is interested in the use of mesenchymal stem cells to treat heart disease.36 Mesenchymal stem cells are a specialized form of stem cells that have traditionally been isolated from bone marrow, but increasingly are being isolated from fat,37 which is more convenient and less invasive. Macrophages are immune system cells that can be either pro-inflammatory and destructive, or anti-inflammatory and reparative. Mesenchymal stem cells can determine which type of macrophage manifests.38 Using human stem cell cultures, Dr. Leor showed that mesenchymal stem cells from fat could promote anti-inflammatory macrophage development. 39 Using mesenchymal stem cells from the bone marrow of mice he demonstrated the ability of those cells to induce repair of experimentally-produced heart damage in mice.40 Later, using cells isolated from human patients, he was able to show that mesenchymal stem cells isolated from fat near the heart were more likely to induce pro-inflammatory macrophages, whereas mesenchymal stem cells from subcutaneous fat (fat under the skin) induced anti-inflammatory properties.41 So it appears that mesenchymal stem cells from subcutaneous fat have potential for treatment of heart attack victims.


Rejuvenation Of Immune System B-Cells

Doron Melamed, PhD (Professor, Technion ― Israel Institute of Technology, Haifa, Israel) is concerned with why the adaptive immune system declines in function with age, rendering vaccination of the elderly less effective than vaccination of the young. Many tissues of the body are continuously replenished by stem cells. Over a period of about two months, skin cells in the epidermis are shed and replenished by stem cells. Red blood cells last about four months before they are replenished by stem cells. The white blood cells (leukocytes) of the adaptive immune system are not continuously replenished, however, because they must maintain immunity over the life span of the organism.42 Vaccination is thus less effective in the elderly. 43 Dr. Melamed has attempted to understand the mechanism by which the adaptive immune system ages.44 The adaptive immune system consists primarily of T-cells (which mature in the thymus gland) and B-cells (which mature in bone). B-cells produce antibodies that are used by T-cells to identify and destroy virus-infected cells and cancer cells. Part of the reason that T-cells age is that the thymus gland begins shrinking at puberty. Dr. Melamed has focused his attention on why B-cells age. He has shown that he could rejuvenate B-cells in mice simply by removing the existing B-cells.42,45,46, The stem cells that create new B-cells retain their capacity to do so even in old age. The same technique could not be used to rejuvenate T-cells, however, because of the degeneration of the thymus gland after puberty.

Cytomegalovirus Is Not Harmless


Graham Pawelec, PhD (Professor, University of Tubingen, Tubingen, Germany) specializes in aging of the immune system due to cytomegalovirus (CMV). CMV can be a life-threatening virus even for those with a healthy immune system.47 Like herpes simplex virus, CMV is usually inactive in infected persons, but is never eliminated by the immune system. Unlike herpes simplex, however, a substantial portion of the immune system is involved in controlling CMV, which drains the resources of the immune system.48,49 Dr. Pawelec noted that death rates in people as a result of cancer and cardiovascular disease cease accelerating by age 75-80, but death rates from infectious diseases continue to accelerate with age indefinitely.50 Persons with the highest levels of CMV antibodies have a much higher risk of death from all causes than persons with few or no antibodies.51,52 CMV is pro-inflammatory, which helps to explain its contribution to immunosenescence and potential relationship with other pathologies.53,54 CMV prevalence increases with age, leveling off at about 85-90% of the population being infected by age 75-80.55 Dr. Pawelec’s team has found that a lower responsiveness to vaccination is associated with CMV infection.56 His team has also found that families having longevity genes have lower levels of CMV-associated alterations in immune function.57 Efforts to develop a vaccine against CMV have not yet been successful.58,59 CMV is transmitted through body fluids such as blood, urine, saliva, vaginal secretions, and semen. Infants are often newly infected, and therefore infectious. Infant caregivers should wash themselves thoroughly with soap and water after changing diapers, feeding, or handling toys. The drug valganciclovir can eradicate active CMV infection.60

Life Extension Contributions To Modern Medicine

Life Extension Contributions To Modern Medicine  

Ilia Stambler, PhD (Researcher, Bar-Ilan University, Tel Aviv, Israel) is a historian of life-extension science.61 The theme of his presentation was that many modern medical therapies had their origin in the efforts of early scientists to find methods of rejuvenation or life extension. Modern hormone replacement therapy originated from 19th century efforts to rejuvenate men using testicular extracts from animals. Similarly, some of the first transplantation operations were attempts at rejuvenation by transplantation of sex glands. Nobel Prize winning researcher Alexis Carrel fostered the idea that cells are immortal in cell culture. Although his techniques proved to be flawed, Carrel was an important contributor to the practice of culturing cells in a growth medium. The first academic institution devoted to blood transfusion was founded in 1925 by a Russian physician who was seeking rejuvenation. Dr. Stambler credits Alexander Bogomolets, a Soviet-era President of the Academy of Sciences of Ukraine, with the use of adjuvants (added components) to potentiate the immune response of the body. Dr. Bogomolets was an ardent life extension proponent. In 1938 Bogomolets organized the first publicized gerontological conference, and he also published his book The Prolongation of Life.

Conference Coverage In The Israeli Media

Dr. Stambler is himself an enthusiastic life extensionist. He was on the organizing committee of this conference. His promotion of the conference in Israeli television and newspapers emphasized the possibilities of life extension. He estimates that these media exposures reached nearly a fifth of the population of Israel.

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


  1. Seluanov A, Chen Z, Hine C, et al. Telomerase activity coevolves with body mass not lifespan. Aging Cell. 2007 Feb;6(1):45-52.
  2. Seluanov A, Hine C, Azpurua J, et al. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat. Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19352-7.
  3. Tian X, Azpurua J, Hine C, et al. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature. 2013 Jul 18;499(7458):346-9.
  4. Azpurua J, Ke Z, Chen IX, et al. Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17350-5.
  5. Breakthrough of the year 2013. Notable developments. Science. 2013 Dec 20;342(6165):1435-41.
  6. Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010 Apr 16;328(5976):321-6.
  7. De Grey AD. Calorie restriction, post-reproductive life span, and programmed aging: a plea for rigor. Ann N Y Acad Sci. 2007 Nov;1119:296-305.
  8. Colman RJ, Anderson RM, Johnson SC, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4.
  9. Mattison JA, Roth GS, Beasley TM, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012 Sep 13;489(7415):318-21.
  10. Duffy PH, Seng JE, Lewis SM, et al. The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: implications for chronic studies. Aging (Milano). 2001 Aug;13(4):263-72.
  11. Raatz SK, Silverstein JT, Jahns L, Picklo MJ. Issues of fish consumption for cardiovascular disease risk reduction. Nutrients. 2013 Mar 28;5(4):1081-97.
  12. Nicholson T, Khademi H, Moghadasian MH. The role of marine n-3 fatty acids in improving cardiovascular health: a review. Food Funct. 2013 Feb 26;4(3):357-65.
  13. Lane MA, Ingram DK, Roth GS. 2-Deoxy-D-glucose feeding in rats mimics physiologic effects of calorie restriction. J Anti-Aging Med. 1998 Winter;1(4):327-37.
  14. Rajpathak SN, Liu Y, Ben-David O, et al. Lifestyle factors of people with exceptional longevity. J Am Geriatr Soc. 2011 Aug;59(8):1509-12.
  15. Sanders AE, Wang C, Katz M, et al. Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia. JAMA. 2010 Jan 13;303(2):150-8.
  16. Schechter CB, Barzilai N, Crandall JP, Atzmon G. Cholesteryl ester transfer protein (CETP) genotype and reduced CETP levels associated with decreased prevalence of hypertension. Mayo Clin Proc. 2010 Jun;85(6):522-6.
  17. Atzmon G, Rincon M, Schechter CB, et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol. 2006 Apr;4(4):e113.
  18. Atzmon G, Schechter C, Greiner W, Davidson D, Rennert G, Barzilai N. Clinical phenotype of families with longevity. J Am Geriatr Soc. 2004 Feb;52(2):274-7.
  19. Atzmon G, Rincon M, Rabizadeh P, Barzilai N. Biological evidence for inheritance of exceptional longevity. Mech Ageing Dev. 2005 Feb;126(2):341-5.
  20. Tabatabaie V, Atzmon G, Rajpathak SN, Freeman R, Barzilai N, Crandall J. Exceptional longevity is associated with decreased reproduction. Aging (Albany NY). 2011 Dec;3(12):1202-5.
  21. Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9.
  22. Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013 Jan 24;49(2):359-67.
  23. Mercer TR, Neph S, Dinger ME, et al. The human mitochondrial transcriptome. Cell. 2011 Aug 19;146(4):645-58.
  24. Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013 Jan 11;50(1):R11-9.
  25. Muzumdar RH, Huffman DM, Atzmon G, et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One. 2009 Jul 22;4(7):e6334.
  26. Widmer RJ, Flammer AJ, Herrmann J, et al. Circulating humanin levels are associated with preserved coronary endothelial function. Am J Physiol Heart Circ Physiol. 2013 Feb 1;304(3):H393-7.
  27. Thompson LV. Age-related muscle dysfunction. Exp Gerontol. 2009 Jan-Feb;44(1-2):106-11.
  28. Shefer G, Van de Mark DP, Richardson JB, Yablonka-Reuveni Z. Satellite-cell pool size does matter: defining the myogenic potency of aging skeletal muscle. Dev Biol. 2006 Jun 1;294(1):50-66.
  29. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol. 2007 Jan;211(2):144-56.
  30. Warren LA, Rossi DJ. Stem cells and aging in the hematopoietic system. Mech Ageing Dev. 2009 Jan-Feb;130(1-2):46-53.
  31. Oikawa A, Siragusa M, Quaini F, et al. Diabetes mellitus induces bone marrow microangiopathy. Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):498-508.
  32. Spinetti G, Cordella D, Fortunato O, et al. Global remodeling of the vascular stem cell niche in bone marrow of diabetic patients:implication of the microRNA-155/FOXO3a signaling pathway. Circ Res. 2013 Feb 1;112(3):510-22.
  33. Mangialardi G, Katare R, Oikawa R, et al. Diabetes causes bone marrow endothelial barrier dysfunction by activation of the RhoA-Rho-associated kinase signaling pathway. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):555-64.
  34. Krizhanovsky V, Yon M, Dickins RA, et al. Senescence of activated stellate cells limits liver fibrosis. Cell. 2008 Aug 22;134(4):657-67.
  35. Sagiv A, Biran A, Yon M, Simon J, Lowe SW, Krizhanovsky V. Granule exocytosis mediates immune surveillance of senescent cells. Oncogene. 2013 Apr 11;32(15):1971-7.
  36. Gnecchi M, Danieli P, Cervio E. Mesenchymal stem cell therapy for heart disease. Vascul Pharmacol. 2012 Aug 19;57(1):48-55.
  37. Ong WK, Sugii S. Adipose-derived stem cells: fatty potentials for therapy. Int J Biochem Cell Biol. 2013 Jun;45(6):1083-6.
  38. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One. 2010 Apr 26;5(4):e10088.
  39. Adutler-Lieber S, Ben-Mordechai T, Naftali-Shani N, et al. Human macrophage regulation via interaction with cardiac adipose tissue-derived mesenchymal stromal cells. J Cardiovasc Pharmacol Ther. 2013 Jan;18(1):78-86.
  40. Ben-Mordechai T, Holbova R, Landa-Rouben N, et al. Macrophage subpopulations are essential for infarct repair with and without stem cell therapy. J Am Coll Cardiol. 2013 Nov 12;62(20):1890-901.
  41. Naftali-Shani N, Itzhaki-Alfia A, Landa-Rouben N, et al. The origin of human mesenchymal stromal cells dictates their reparative properties. J Am Heart Assoc. 2013 Sep 30;2(5):e000253.
  42. Keren Z, Averbuch D, Shahaf G, et al. Chronic B cell deficiency from birth prevents age-related alterations in the B lineage. J Immunol. 2011 Sep 1;187(5):2140-7.
  43. Lang PO, Govind S, Mitchell WA, Siegrist CA, Aspinall R. Vaccine effectiveness in older individuals: what has been learned from the influenza-vaccine experience. Ageing Res Rev. 2011 Jul;10(3):389-95.
  44. Melamed D, Scott DW. Aging and neoteny in the B lineage. Blood. 2012 Nov 15;120(20):4143-9.
  45. Mehr R, Melamed D. Reversing B cell aging. Aging (Albany NY). 2011 Apr;3(4):438-43.
  46. Keren Z, Naor S, Nussbaum S, et al. B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging. Blood. 2011 Mar 17;117(11):3104-12.
  47. Heininger A, Haeberle H, Fischer I, et al. Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis. Crit Care. 2011;15(2):R77.
  48. Hadrup SR, Strindhall J, Køllgaard T, et al. Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol. 2006 Feb 15;176(4):2645-53.
  49. Derhovanessian E, Maier AB, Hähnel K, et al. Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans. J Gen Virol. 2011 Dec;92(Pt 12):2746-56.
  50. Pawelec G, Koch S, Franceschi C, Wikby A. Human immunosenescence: does it have an infectious component? Ann N Y Acad Sci. 2006 May;1067:56-65.
  51. Roberts ET, Haan MN, Dowd JB, Aiello AE. Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol. 2010 Aug 15;172(4):363-71.
  52. Simanek AM, Dowd JB, Pawelec G, Melzer D, Dutta A, Aiello AE. Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS One. 2011 Feb 17;6(2):e16103.
  53. Pawelec G, Larbi A, Derhovanessian E. Senescence of the human immune system. J Comp Pathol. 2010 Jan;142 Suppl 1:S39-44.
  54. Derhovanessian E, Maier AB, Hähnel K, et al. Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people. Age (Dordr). 2013 Aug;35(4):1387-99.
  55. Pawelec G, McElhaney JE, Aiello AE, Derhovanessian E. The impact of CMV infection on survival in older humans. Curr Opin Immunol. 2012 Aug;24(4):507-11.
  56. Derhovanessian E, Theeten H, Hähnel K, Van Damme P, Cools N, Pawelec G. Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination. Vaccine. 2013 Jan 11;31(4):685-90.
  57. Derhovanessian E, Maier AB, Beck R, et al. Hallmark features of immunosenescence are absent in familial longevity. J Immunol. 2010 Oct 15;185(8):4618-24.
  58. Khanna R, Diamond DJ. Human cytomegalovirus vaccine: time to look for alternative options. Trends Mol Med. 2006 Jan;12(1):26-33.
  59. Lilja AE, Mason PW. The next generation recombinant human cytomegalovirus vaccine candidates-beyond gB. Vaccine. 2012 Nov 19;30(49):6980-90.
  60. Available at: Accessed February 19, 2014.
  61. Available at: Accessed February 17, 2014.