Senescence surveillance of pre-malignant hepatocytes limits liver cancer development


Tae-Won Kang, Tetyana Yevsa, Norman Woller, Lisa Hoenicke, Torsten Wuestefeld, Daniel Dauch, Anja Hohmeyer, Marcus Gereke, Ramona Rudalska, Anna Potapova, Marcus Iken, Mihael Vucur, Siegfried Weiss, Mathias Heikenwalder, Sadaf Khan, Jesus Gil, Dunja Bruder, Michael Manns, Peter Schirmacher, Frank Tacke, Michael Ott, Tom Luedde, Thomas Longerich, Stefan Kubicka & Lars Zender

Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo1. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this ‘secretory phenotype’ can have pro- as well as anti-tumorigenic effects2, 3, 4, 5. Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines and are subject to immune-mediated clearance (designated as ‘senescence surveillance’), which depends on an intact CD4+ T-cell-mediated adaptive immune response. Impaired immune surveillance of pre-malignant senescent hepatocytes results in the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of NrasG12V. We also found that CD4+ T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells.


Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders

A paper worth reading. Excellent work.


Darren J. Baker, Tobias Wijshake, Tamar Tchkonia, Nathan K. LeBrasseur, Bennett G. Childs, Bart van de Sluis, James L. Kirkland & Jan M. van Deursen

Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells1, 2. Senescent cells accumulate in various tissues and organs with ageing3 and have been hypothesized to disrupt tissue structure and function because of the components they secrete4, 5. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16Ink4a, to design a novel transgene, INK-ATTAC, for inducible elimination of p16Ink4a-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16Ink4a-positive senescent cells upon drug treatment. In tissues—such as adipose tissue, skeletal muscle and eye—in which p16Ink4a contributes to the acquisition of age-related pathologies, life-long removal of p16Ink4a-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.


Cellular Senescence and COPD

Chronic obstructive pulmonary disease (COPD) is characterized by progressively reduced airflow within the lungs, making it difficult to breath. During normal breathing, air sacs (alveoli) (which are elastic) fill up with air and oxygen passes through the air sac walls into the blood. With COPD the air sacs can lose elasticity, the walls between air sacs are destroyed, the walls become thick and inflamed and the airways make more mucus than normal leading to clogging. All these changes contribute to reduced airflow in COPD.

COPD is predominately associated with tobacco smoking and previous studies investigating the pathophysiology of emphysema have demonstrated that cigarette smoke can cause cells to enter cellular senescence (Tsuji et al, 2004, Nyunoya et al 2006). As such, a number of studies have investigated the role of cellular senescence in the development and progression of COPD. Cigarette smoke may trigger cells to senesce directly due to DNA damage or indirectly (if apoptosis is occurring) through increasing cell turnover leading to accelerated telomere shortening.

Senescent cells secrete pro-inflammatory cytokines, growth factors and proteases (most likely for immune clearance) that can cause tissue damage, leading to loss of function of the tissue in which they reside. In the case off COPD the secretion of proteases by senescent cells could result in loss of elasticity of air sacs and destruction of air sac walls. The secretion of cytokines and chemokines by senescent cells would lead to persistent inflammation.

Tsuji et al (2009) has shown that lung tissue of COPD patients contained higher percentages of senescent alveolar cells displaying a pro-inflammatory phenotype compared with tissue from asymptomatic smokers and non-smokers. Noureddine et al (2011) has demonstrated that pulmonary artery smooth muscle cell (PA-SMC) senescence is an important contributor in the process of pulmonary vessel remodeling in COPD patients. Senescent PA-SMC were shown to stimulate cell growth and migration of normal PA-SMC through the release of paracrine soluble and insoluble factors. Dogauassat et al (2011) have shown that lung fibroblasts in smokers and ex-smokers with moderate COPD display a senescent phenotype. This study suggests that even after stopping smoking, the persistence of senescent cells may still contribute to COPD. Amsellem et al (2011) have recently showed that premature senescence in pulmonary vascular endothelial cells may contribute to inflammation in COPD.

Research also suggests that patients with COPD have a two to six times more chance of developing lung cancer compared with people of normal lung function (COPD Foundation). It could be speculated that the presence of senescent cells in COPD patients may increase the chances of lung cancer. It has been shown that the secretory phenotype of senescent cells can play a role in cancer development by stimulating growth and angiogenic activity of pre-malignant cells (reviewed in Campisi and d'Adda di Fagagna, 2007). Additionally, stochastic epigenetic/genetic alterations within senescent cells may allow them to escape the senescence growth arrest, thus becoming cancerous.


Tsuji T, Aoshiba K, Nagai A. Alveolar cell senescence exacerbates pulmonary inflammation in patients with chronic obstructive pulmonary disease. Respiration. 2010;80(1):59-70. Epub 2009 Dec 17.

Noureddine H, Gary-Bobo G, Alifano M, Marcos E, Saker M, Vienney N, Amsellem V, Maitre B, Chaouat A, Chouaid C, Dubois-Rande JL, Damotte D, Adnot S. Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for pulmonary hypertension in chronic lung disease. Circ Res. 2011 Aug 19;109(5):543-53. Epub 2011 Jun 30.

Amsellem V, Gary-Bobo G, Marcos E, Maitre B, Chaar V, Validire P, Stern JB, Noureddine H, Sapin E, Rideau D, Hue S, Le Corvoisier P, Le Gouvello S, Dubois-Randé JL, Boczkowski J, Adnot S. Telomere Dysfunction Causes Sustained Inflammation in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2011 Sep 8. [Epub ahead of print]

immune clearance of senescent and cancer cells

The age-associated increase in the incidence of disease development and cancer occurrence is often thought to be due to the gradual accumulation of damage over the lifetime of an organism. However, an alternative opinion is that damaged cells are effectively eliminated and replaced by the immune system and regenerative cells (stem cells) and only when this “remove and replace” system failures, do organisms begin to show signs of ageing.

The presence of persistent DNA damage triggers cells to enter senescence (irreversible growth arrest) to protect the cell from becoming cancerous. The presence of the persistent DNA damage in these growth-arrested cells appears to activate pathways leading to cytokine/chemokine secretion and presentation of cell surface ligands (i.e MICA, MICB, ULBP2) which can be recognized by natural killer cells (NK) and some T-cells. This may allow damaged/senescent cells to communicate with immune cells for their removal (although more evidence of this is required).

For cells to become cancerous, they need to bypass senescence (following irreparable DNA damage), often achieved by acquiring mutations in genes associated with activation and maintenance of the senescence growth arrest. When such cells bypass senescence, the persistence of DNA damage may also activate pathways leading to cytokine/chemokine secretion and presentation of NK ligands.

It is also possible that cells can become cancerous if they instead escape senescence. “Escaping” is different from “bypassing” in that these cells were once senescent. If senescent cells persist in tissues without immune clearance, it is possible that stochastic genetic/epigenetic changes may lead to activation/inactivation of genes that allow the once senescent cell to reneter the cell cycle. A consequence of this escape may be the maintenance of the pro-survival phenotype and the pro-inflammatory phenotype associated with senescence. Escaping senescence may be more pertinent in cancer cells that have become senescent in response to therapy. Escape from senescence in this instance may lead to the progression of more aggressive cancers.

I am not aware of any studies that have investigated the similarities/differences in the secretory phenotype/NK ligand activation of senescent verses cancer cells. However, if both exist due the DNA damage response activating the immune response (DDR-AIR), then they are probably very similar.

If senescent and cancer cells were always effectively being removed then the incidence of cancer and disease would greatly be reduced. However, age-associated cancer and disease does occur and this may in part be due to a failure in the immune system to effectively remove senescent/cancer cells as we age. Additionally, cancer cells can develop various strategies for evading the immune response (i.e secretion of immunosuppressive cytokines). Whether the same strategies occur in senescent cells remains to be discovered.

Although purely speculative, it is possible that some of these strategies for evading immune surveillance is a result of pro-longed exposure to the pro-inflammatory phenotype of these cells. There may be a limited biological time frame whereby the presence of the inflammatory phenotype is beneficial for cell removal. Longer exposure may lead to an adaptive response through autocrine signalling leading to changes that evade immune surveillance. For example, the secretion of immunosuppressive cytokines may be an adaptive response for preventing detrimental damage from long exposure to pro-inflammatory cytokines.

Ongoing and future investigations should aim to provide solid evidence of whether (1) the secretory phenotype of senescent cells is for the purpose of immune clearance, (2) and if so, does immune clearance fail or become impaired with age and (3) if it does fail, what are the mechanisms?

Suggested readings

Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature. 2005 Aug 25;436(7054):1186-90. Epub 2005 Jul 3.

Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008 Dec 2;6(12):2853-68.

Seliger B. Strategies of tumor immune evasion. BioDrugs. 2005;19(6):347-54.

Wang Q, Wu PC, Roberson RS, Luk BV, Ivanova I, Chu E, Wu DY. Survivin and escaping in therapy-induced cellular senescence. Int J Cancer. 2011 Apr 1;128(7):1546-58. doi: 10.1002/ijc.25482. Epub 2010 May 25.

Stem Cell Backup: Bank your cells for the future

The following is a brief article provided by Stem Cell Backup (click here), which discusses the importance of banking your cells for future therapeutic applications.

Growing replacement ears for injured soldiers. Allowing the paralyzed to walk again. Restoring sight to the blind. Curing multiple sclerosis. Growing transplantable lungs. This, and more, is being done today. The magic technology? The most basic there is, the patient's own cells. You are witnessing the dawn of a new era of medicine. Regenerative medicine—using your own stem cells to heal yourself—is no longer science fiction. The U.S. Department of Health and Human Services reports that “regenerative medicine is the vanguard of 21st century health care.” These experts estimate that half of Americans now under the age of 65 will receive regenerative therapies during their lifetime. Simultaneously, groundbreaking advances now mean scientists can use your own non-stem cells to make the stem cells used in regenerative medicine.

In 2006 a Japanese researcher did something that most researchers considered impossible, he 'reprogrammed' a normal skin cell and made it into a stem cell. The new technique was so effective and technically simple that thousands of research laboratories soon began using these 'induced' pluripotent stem cells (iPSC). Even the scientist who cloned Dolly the sheep abandoned cloning, saying "[Reprogramming is] 100 times more interesting [than cloning]…I have no doubt that in the long term, direct reprogramming will be more productive” (London Telegraph 11/10/08).

High expectations, to be sure, but iPSC are already exceeding them. Researchers have treated or even fully cured maladies like Parkinson's, heart attack damage and diabetes in test animals using iPSC. Additionally, iPSC have also been used to grow dozens of types of transplantable tissue, like retinas, and even fully-functioning organs, like livers. Medical experts expect iPSC to play a role in virtually every medical treatment of the future.

To help you take advantage of these dual advances, Stem Cell Backup banks your cells for your future use. Like many things in life, age matters. Research shows that cells taken from older patients are less effective for therapeutic use. By banking your own youngest, healthiest cells you can grow any kind of new tissue you need, whether heart, liver, or muscle.

"You are seeing the birth of a new industry," says Patrick O'Malley, president of Stem Cell Backup, "that has a strong precedent in the long-established cord blood industry. In the U.S. alone, over one million families currently bank their newborn child’s umbilical cord blood for future medical treatments. Banking your own cells is like cord blood for the rest of us." Mr. O’Malley points to the universal consensus of medical experts who expect great things from this new form of personalized medicine, "Every knowledgeable expert says that this technology is transformational. The Nobel Laureate for Medicine said, 'This is going to be the way forward. …We’ve all been waiting for this' (WSJ 11/21/07). Doctor Oz predicted on Oprah that a patient’s own cells will be used to cure Parkinson's disease in 8 or 9 years."

Stem Cell Backup was founded in 2008 to allow individuals to take advantage of new discoveries in stem cell medicine. After extensive research and testing, the company began accepting client samples in 2011. Stem Cell Backup is the first and only company to allow individuals to easily, safely, and inexpensively save their own cells for use in future medical therapies. It has a processing laboratory in the U.S. and is currently identifying local partner candidates in European and Asian markets.

For those who want to take advantage of this unique service, visit for further details.

23andme: Using Personal Genome Analysis (PGA) for Promoting Healthier Longer Lives

I recently got my genome analysis results back from 23andme. 23andme analyse your genome for single nucleotide polymorphisms (SNPs), variations in single nucleotides, which can correlate with disease, drug response and other phenotypes.
Personal genome analysis (PGA) will revolutionize how we think about our own health. Currently, whenever a symptom or illness presents itself, we see doctors and those doctors provide medicines and treatments to remove or control the problem. With PGA we can discover what diseases we may be at risk of developing and in some cases adjust our lifestyles to reduce/prevent disease occurrence/progression.
For example, my PGA suggests (based on a number of studies) that I am at risk of developing a mild form of hemochromatosis, a disorder in which the body absorbs too much iron, causing damage to tissues, specifically the liver. A fact I find rather amusing considering I nearly started a research project focused on the role of iron in ageing.
Knowing I may be at risk of hemochromatosis, I can alter my diet to avoid foods such as red meats, which have a high percentage of iron. Thus, having this genetic knowledge could postpone/prevent the appearance of a disease by taking the appropriate steps. Prevention of disease, means healthier, longer lives.
There have also been a few studies looking at SNP’s associated with longevity. One study compared 213 Ashkenazi Jewish subjects ranging in age from 95 to 107 to a group of counterparts about 30 years their junior. Members of the longer-lived group were more likely to have a C in both copies of the SNP rs2542052. People with this genetic signature tended to be more sensitive to insulin and were less likely to have high blood pressure, which suggests it may promote longevity by protecting against cardiovascular disease. Luckily for me, my PGA is telling me I have two copies C.
Another study, which is more related to longevity in the Asian population, compared 213 Japanese men who lived 95 years or longer to 402 Japanese men who died before the age of 81. The researchers found that the longer-lived Japanese men were more likely to have a C at one or both copies of rs2764264, a SNP in the FOXO3A gene. Each C at rs2764264 was associated with about 1.6 greater odds of reaching age 95 or beyond compared to having a T at this position. The FOXO3A gene has been shown to modulate longevity in laboratory animals. Again, I have two copies of C (although in this instance, it may be ethnicity specific).
Readers must take into account that these studies were based on a limited number of participants and environmental factors such as diet are probably just as, if not more important than the underlying genetics. But that is a debate for another time.
Unfortunately it may not all be good news, I found out I have an increased chance of developing male pattern baldness…..thanks Dad :-)
If you are someone who have either bought a genetic test from a company like 23andme, or are thinking of doing so, please help out Corin Egglestone, a PhD student from Loughborough University in the UK, by spending 10 minutes of your time to answer questions for her survey:

Novelli V et al. (2008) . “Lack of replication of genetic associations with human longevity.” Biogerontology 9(2):85-92.
Atzmon G et al. (2006) . “Lipoprotein genotype and conserved pathway for exceptional longevity in humans.” PLoS Biol 4(4):e113.
Willcox BJ et al. (2008) . “FOXO3A genotype is strongly associated with human longevity.” Proc Natl Acad Sci U S A 105(37):13987-92.

Guest Blog: Harold Katcher: Is Prevention of Ageing within our Grasp?


Slowly but steadily knowledge about the human body has progressed and new ideas of animal ageing have immerged. The classic model of ageing, based on “accumulation of errors” has become an outdated notion. Instead, evidence suggests that ageing, at least in part, is likely the result of a failure in the function of cells (such as stem cells) required for cellular regeneration. Replacing impaired stem cells with fully functional stem cells should thus prevent/treat age-associated pathologies allowing us to live healthier longer lives.

What We Think We Know

We were once taught that the essential differences between animals and plants were that plants are mostly non-living, except for a layer or bud of special cambium cells, called meristems; unlike animals, plants grew from their outside surfaces and tips – while animals grew from the inside by the division of somatic cells. These notions have since been replaced with one in which specialized cells, called stem cells, (the animals' “meristematic” tissue) or progenitor cells (like stem cells, only less pleuripotent and of a limited lifespan), that can differentiate into, and replace, various diverse cell-types, (in contrast to somatic cells which cannot). (Janzen et al 2006). It has become clear that the many impairments of the ageing body are due to ageing stem/progenitor cell populations.

For example, muscle loss in the elderly (sarcopenia) appears to be the result of decreasing numbers of stem cells. (Hawke T.J..& Garry, D.J-. 2001). Muscle satellite cells which lie between the sarcolemma and the basement membrane of terminally differentiated muscle fibers, provide muscle precursor cells that are then incorporated into muscle fibers (Mauro, A . 1961). Satellite cells from aged individuals display an impaired proliferative ability when compared with satellite cells from a young individual, thus possibly resulting in sarcopenia. In organs like the liver that depend on progenitor cells for tissue repair and replacement, progenitor cell impairment would also result in deficiencies in wound healing and thus presentation of age-associated pathologies.

The loss of immune function, commonly observed within the elderly, makes them more susceptible to various diseases, infections and cancers. As in the case of ageing tissues, a lack of functional cells characterizes an aged immune system. Conversely, in this instance, stem cell populations do not decline, but instead there is an increase in the stem cell populations (i.e. hematopoietic stem cells, HSCs) that reside within the bone marrow (Sudo et al. 2000). However, unlike young HSCs, the ratio of the many potential cell-types that the HSC population generates changes with ageing. For example, aged HSCs move away from production of lymphoid line cells (T and B lymphocytes and NK cells) and towards the production of myeloid line cells (monocyte/macrophages, RBC, thrombocytes, granulocytes) cells. This age-associated reduction lymphoid cells, which forms the adaptive immune system, is thought to result in the age-associated decreased immune response (Chambers et al. 2007). The increased fraction of myeloid precursor HSCs appears to contribute to the myeloid leukemias that occur among the elderly (Rossi et al.).

So how can we combat the effects of functionally declining stem/progenitor stem cell populations? Solutions such as stem cell cloning and telomere elongation through telomerase therapy have been suggested, but is this really necessary? Is there a way to rejuvenate aged stem cells from within out own bodies, giving them the ability to constantly maintain high cell numbers in the organs they populate, cells with high proliferative capacity, rapid responses to wounding? It has become apparent that this possibility may exist.

A New Paradigm - Evidence accumulates

Several line of evidence suggest that the standard model of ageing, based on “error accumulation” is incorrect. Several studies in which tissues or organs are transplanted from donor animals have shown that the ability of the graft to be successful (by measures of ability to proliferate or recover from wounds) depends not on the donor's age, but on the age of the recipient. Such studies have shown that HSCs from aged immunodeficient donors gave normal responses in young recipients (Harrison et al 1977), and that aged HSCs could be coaxed to produce lymphoid cells by being placed together with young osteolineage cells (Mayack, S,R. And Wagers, A. 2008). Additionally, transplanted aged muscle responded to the internal environment of a young recipient by showing the same sort of wound- repair as young muscle.

The most important experiment investigating the effect of environment (specifically the humoral environment) was performed in 2007 by Irina Conboy and a later confirmation came with experiments performed by Mayack's group in 2010. While earlier in vivo experiments showed that tissues and organs obtained from aged donors could effectively be rejuvenated by being placed in the bodies of young recipients, it was not clear which factors were acting to rejuvenate these aged organs. Were there local tissue interactions, were there positive factors in young recipients that caused a revitalization of the old organs, or perhaps negative factors in aged bodies preventing cells from proliferating? Were cells from the young recipients colonizing these aged organs? How much did the environment of the aged cells influence their phenotype?

Conboy et al (2005) used a procedure called parabiosis (Finerty, J. 1952) to pair the circulatory systems of two mice. They now effectively shared the same blood, but not interactions between tissues of the parabionts (other than blood cells), thereby narrowing down the possible factors influencing the cells of the parabionts. In a nicely controlled experiment, mice were paired in either isochronic parabiosis or heterochronic parabiotic associations – in the isochronic cases two mice of the same age were tied together – either a young-young pairing or an old-old pairing and the heterochronous association a young mouse (2-3 months) was coupled to an old mouse (19-26 months) and were kept in this pairing for five weeks. After that time, it was found that in heterochronic pairings, but not in isochronic pairings old muscle satellite cells returned to youthful performance in terms of effecting wound healing and increased proliferative capacity. Another insightful experiment narrowed the range of responsible factors. In vitro experiments showed that exposure of aged cells to young serum was sufficient to rejuvenate aged HSCs, muscle satellite stem cells as well as liver progenitor cells. As the paired mice parabionts have distinctive chromosomal markers it was assured that the old organs weren't being colonized by young cells.

Further experiments extending the concept that the environment controlled the age-phenotype of the cell, was provided by Mayack et al (2010). Mayack used Conboy's method of parabiosis together with parallel in vitro studies using serum to provide the external environment. Both sets of experiments also showed that young serum was caple of rejuvenating aged HSCs. Mayack's group however showed that the cells rejuvenated by the young environment were the bone stromal cells. It was these rejuvenated stromal cells that later interacted with aged HSCs to set back their phenotypic-age. The parallel in vivo/in vitro experiments performed by these groups showed that the rejuvenation of cells was a function of a factor or factors carried in the serum. The explanations proposed; that either young blood diluted inhibitory factors present in aged blood, or brought new levels of stimulatory factors carried by young blood, or both.

While neither experiment could discriminate between these alternatives, both showed that the cells' environment was responsible for an ageing-phenotype (the panoply of genes expressed, its proliferative potential, various molecular markers of ageing). The one conclusion that can be taken for certain is that factors in the blood of the young animal were able to rejuvenate a variety of different stem/ progenitor cell lines in vivo, and that, in particular, as show by the in vitro experiments, factors present in the serum of young animals rejuvenate the stem and progenitor cells of aged animals. The conclusion reached by the groups involved in this research was that blood borne determinants, both positive and negative might be isolated, and eventually added to or removed from the blood of the ageing. So for the first time in history, there is a reasonable prospect to achieve what mankind has sought for all of history. There may finally be a therapeutic approach for the treatment of ageing and thus, disease. Evidence of such inhibitory factors in the blood of aged mice (McCay et al. 1957) and stimulatory factors in the serum of young mice (Hadad et al 1988), have already been detected.


The answers to extending healthy life span is now within our grasp – what if our own stem cells could be rejuvenated? With only the four cell types proven to be “rejuvenate-able”, (1) muscle loss could be eliminated, (2) the immune system made effective again, (3) bone now capable of making osteoblasts for growth and strength and (4) the liver able to perform its functions as in youth. Other cell types may also be positively influenced, leading to youthful changes such as, new hair growth, smooth skin, improved memory from neuron regeneration. The possibilities are endless. If viewed in this light, it is obvious what should be done – this new model should be tested and tested on people – and the means to test it? A practical medically approved procedure, cheap while being at the same time, able to provide all of the factors needed to rejuvenate cells is available right now! This is a procedure that any consenting physician could perform tomorrow.

I am not going to talk about it now – like all great secrets, once told it becomes obvious –“ no duh, why hasn't it already been tried.” Join me and we'll perhaps try it together. (

Papers of Interest

Chambers, S.M. et al. Ageing hematopoietic decline in function and exhibit epigenetic dysregulation. PLOS Biology (5) e201

Conboy et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment Nature (433) 760 -764 (2005)

Finerty, J. Parabiosis in physiological studies Physiol. Rev. (32) 277 – 302 (1952)

Hadad, E. J. et al Lymphocyte induced angiogenesis factor is produced by L3T4 murine lymphocytes and its production declines with age. Cancer Immunol Immunother (26) 31- 34 (1988)

Harrison et. al. Stem cell lines from an old immunodeficient donors give normal response in young J. Immunology (118)1223 – 1228 (1977)

Hawke, T.J. And Garry, D.J. Myogenic satellite cells: physiology to molecular biology J. Appl. Physiol (91) 534 – 551 (2001)

Janzen, V. et al. Stem-cell ageing modified by the cyclin-dependant kinase inhibit p12INK4a . Nature (443) 421- 426 (2006)

Mauro, A. Satellite cell of skeletal muscle fibers. J. Biolphys.Biochem. Cytol (9) 493 – 495 (1961)

McCay et al. Parabiosis between young and old rats Gerontologia; (1):7-17 ( 1957)

Mayack, S.R. et al. Systemic signals regulate ageing and rejuvenation of blood stem cell niches Nature (463)495-500 (2010)

Mayack, S.R. & Wagers, A Osteolineage niche cells initiate hematopoietic stem cell mobilization Blood (112) 519 – 532 (2008)

Rossi, D.G., Jamieson, C.H. & Weissman, I.L. Stem cells and the pathways to ageing and cancer. Cell (132) 681-696 (2008)

Sudo, K. et al. Age-associated characteristics of murine hematopoietic stem cells. J. Exp. Med (193) 1273 – 1280 (2000)
The main focus of ageing research is to prevent/combat age-related disease and disability, allowing everyone to live healthier lives for longer.