AGINGSCIENCES™ – Anti-Aging Firewalls™

My last major post traced developments related to a form of progeria (premature aging) known as Hutchinson-Gilford progeria syndrome, or HGPS, for short.  The discussion and comments on this post are leading us down new paths, such as exploring the role of progerin and FTI therapies and seemingly away from the usual theories of aging.  There is also a different rare form of progeria known as Werner Syndrome (WS) that is worth looking at for what it might tell us about normal aging.

WS, sometimes called adult progeria, is characterized by the premature onset of age-related diseases, including inflammatory diseases, atherosclerosis and cancer.  People with WS may develop the symptoms of very old age by the time they turn 30 or 40, including “wrinkled skin, baldness, cataracts, muscular atrophy and a tendency to diabetes mellitus, among others(ref).”  Cells from people with WS when cultured have shorter life spans than cells from normal people.  “In culture, cells obtained from patients with WS are genetically unstable, characterized by an increased frequency of nonclonal translocations and extensive DNA deletions(ref).”  It has recently been shown that WS is due to a mutation in a gene called WRN.  It is a hellicase deficiency disease.  Hellicases are enzymes important for many cellular processes including “DNA replication, transcription, translation, recombination, DNA repair, and ribosome biogenesis.”  Normally, the WRN gene “ functions as a key factor in resolving aberrant DNA structures that arise from DNA metabolic processes such as replication, recombination and/or repair, to preserve the genetic integrity in cells(ref).”

Unlike the case for HGPS, there appears to be a direct link between the aging mechanisms operating in WS patients and at least one of the usual theories of aging, the telomere shortning and damage theory. For example, regarding study of a mouse model of WS the authors write “Recent studies of the telomerase-Werner double null mouse link telomere dysfunction to accelerated aging and tumorigenesis in the setting of Werner deficiency. This mouse model thus provides a unique genetic platform to explore molecular mechanisms by which telomere dysfunction and loss of WRN gene function leads to the onset of premature aging and cancer(ref).”  Some researchers highlight the roles of cell senescence and telomeres in WS: “Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts(ref).”  Normal hellicase structures can be very important for assuring normal telomere structures(ref), a situation not present in WS.  Other researchers believe WS operates primarily through other than telomere erosion or damage:  “–  our data suggest that the abbreviated replicative life span of WS cells is due to a stress-induced, p38-mediated growth arrest that is independent of telomere erosion(ref).”

Looking for bridges between the genetic mechanisms operating in HGPS and those operating in WS:  1  It is easy to find commonality of end-results, specifically premature aging phenotypes like baldness, wrinkled skin and cardiovascular disease, and 2.  The underlying genomic mechanisms themselves are in the first instance quite different; they involve activation of different genes and the actions of different protein products. I do not see any easy “Ah hah, here is the common mechanism of aging involved in HGPS, WS and normal aging.”   Both HGPS and WS suggest means by which normal aging might work and possibly be slowed down, having to do with accumulation of progerin and possible treatment with FTIs in the case of HGPS, and having to do with P38, telomere shortening and telomerase activation in the case of WS.

HGPS, standing for Hutchinson-Gilford progeria syndrome is an extremely rare but well-studied genetic disease. Young children born with HGPS seem to age at an extraordinary rate, exhibit many of the symptoms of old age, become wrinkled and bald, are particularly vulnerable to cardiovascular diseases and usually die of a cardiovascular disease of old age by the age of 14.  Up until about five years ago neither the cause of the disease nor a cure were in sight.  Then a chain of exciting research developments emerged indentifying not only cause and possible cure but also what might amount to a new theory of normal aging.  The developments are complex and the puzzle is still far from complete.  I attempt to summarize them here in simple language and speculate on the implications involved.  I will study these matters further and embody this content into my Anti-Aging Firewalls treatise at some point, possibly as an extension of the 14^th theory, Decline in adult stem cell differentiation, possibly as a new 15^th theory.  So, here is the situation: 

1.    HGPS is caused by a mutation in the LMNA gene which is responsible for making lamin proteins which provide “scaffolding (supporting) components of the nuclear envelope, the structure that surrounds the nucleus in cells.”  The mutation produces a lamin that is “farnesylated but cannot be further processed to mature lamin A.(ref)”  That mutant farnesylated lamin is called progerin.  (Farnesylation is a post-translational chemical modification of a protein involving addition of a farnesyl group.) In progerin, a DNA sequence of 50 amino acids which would normally appear in the lamin is spliced out.

2.   Progerin targets itself to the nuclear envelope of a cell, “where it interferes with the integrity of the nuclear envelope and causes misshapen cell nuclei.” (ref),  There is strong reason to believe it is responsible for the symptoms of HGPS(ref).

3.   An obvious research idea was to see what could happen if the farnesylation of progerin was inhibited.  An exciting development was the discovery that, treating cells misshaped by the expression of progerin, inhibiting farnesylation with a farnesyltransferase inhibitor (FTI) could restore their normal cell shapes(ref,ref,ref,ref).  FTIs block the attachment of the farnesyl chemical group onto progerin. FTIs are a class of recently-developed anti-cancer drugs. 

4.   Sure enough and better yet, using the FTI  drug Tipifarnib (Zarnestra) in a progeria mouse model it was possible to prevent both the onset and late progression of cardiovascular disease(ref). This led to a hope that a cure for human HGPS might be based on use of an FTI.

5.   A clinical trial was launched on May 7, 2007 to test FTI therapy in HGPS patients(ref).  It was difficult finding patients because of the rarity of the disease.  Twenty eight children from 16 countries are participating and the trial is about halfway through.

6.   Progerin appears also to play possibly important similar roles in normal aging(ref).  Biochemical studies sugest that progerin may well cause similar effects in HGPS cells and normal cells and possibly a common molecular mechanism might underlie HGPS-type aging and normal physiological ageing. “Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage.  Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A (progerin) whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging(ref).”

7.   Supporting this idea, recent research indicates that progerin builds up in normal cells with age.  A powerful new technique has been developed for measuring the expression of the progeria gene. . A Swedish research group has found that both normal and progeria cells make larger and larger amounts of progerin RNA as they age(ref).

8.   Supporting this idea even further, research indicates that progerin creates all kinds of downstream biomolecular signaling mischief, including the introduction of errors in the normal differentiation of stem cells.  Progerin interferes with cell division in both HGPS and normal cells(ref).  In one key study(ref), the presence of progerin produced a profound impact on renewal and differentiation of adult mesenchymal stem cells, affecting the rates at which they mature into different tissues. “Our results support a model in which accelerated ageing in HGPS patients, and possibly also physiological ageing, is the result of adult stem cell dysfunction and progressive deterioration of tissue functions.”  

  There are strong hints here of important possibilities

:·        That a 15^th theory of aging exists, stating that aging is due to age-related accumulation of progerin in normal cells which creates age-related damage of all kinds similar to that observed in HGPS and inhibits the normal differentiation of adult stem cells into normal cells.  At present I am not sure the extent to which such progerin accumulation is the cause of or the result of other age-related collateral damage and how serious its impact is.·        That it may be possible to design a therapeutic intervention for normal aging based on use of FTIs.  I am not sure how safe it is to use these for anti-aging purposes  given that farnesylation is important for protein binding and happens as part of normal biochemical body functioning.  I have seen no research on the impacts taking FTIs may have on normal old people or even normal old mice for that matter.

I will be thinking about these matters further and on the lookout for additional research results.  You can expect to hear from me on this subject again soon.

Please chime in!

I have wonderful memories of spending summers at a rustic cottage on tiny Pleasant Lake in Michigan with my aunt Lila and my Uncle Gigi D’Augistino, back when I was a child in the 30s.  Gigi loved his red wine and would sprinkle dried red peppers generously over his pasta.  He would explain that his two doctors constantly gave him conflicting advice.  Dr. Gigante, our family’s traditional Italian-trained doctor, would tell Gigi that if he drank one or two glasses of red wine with every meal and partake of the capsicum pepper he would live a long and healthy life.  His modern American doctor told him that unless he cut out the wine and pepper he would surely die of stomach cancer.  Both doctors turned out to be right.  He died of stomach cancer back around 1965 I would guess at the age of 79, living a long life for back at that time.

Back in the 30s, health effects of red wine and hot peppers only existed in oral folk medicine.  There were no biomolecular theories of what these substances might do, animal experiments or clinical trials.  It was enough for Dr. Gigante to say “Red wine and hot peppers will aid your digestion and might help you live longer.”  Now of course we know about the polyphenols like resveratrol that exist in red wine and have a fairly good picture of how some of them limit inflammation, control apoptosis, fight cancers, affect “longevity genes,” and so forth.  A conflict about the longevity effects of wine still exists (see this post) but without any doubt red wine contains biochemical ingredients that are definitely health-promoting and potentially life-extending.

So much for red wine.  Now how about the red peppers?  It appears that a similar story exists.  Capsicum, the main ingredient in hot peppers, apparently can induce apoptosis in cancer cells (ref)(ref).  The American doctor back in the 30s was telling Gigi  the opposite of what was right about his pepper habits and cancer risk.  “It has been shown to exert biological activities (anticarcinogenic, antimutagenic and chemopreventive) in many cancer cell lines(ref).”  Red peppers are turning out to be hot stuff for cancer prevention.  Oh, a final note for any of you worrying about end-burns.  “There is no scientific evidence that a spicy meal based on red hot chili pepper may worsen hemorrhoidal symptoms and, therefore, there is no reason to prevent these patients from occasionally enjoying a spicy dish if they so wish.(ref)”   

Hmm. I am yearning for a good plate of pasta with meat sauce sprinkled with red peppers tonight!

As time rolls on and new research studies roll in, there appears to be more and more evidence for key role of the nuclear binding factor NF-kappaB in aging.  I have listed some updates on this subject in a previous blog post and treat it in my Anti-Aging Firewalls treatise under the Programmed epigenomic changes theory of aging.  I provide some additional thoughts and research citations on this important subject in this post.

First of all, a bit of additional clarification on what NF-kappaB is.  NF-kappaB  is not a single molecular substance but is “a collective name for inducible dimeric transcription factors composed of members of the Rel family of DNA-binding proteins that recognize a common sequence motif”(ref).  What these proteins share in common is a motif, e.g. a characteristic DNA binding sequence.  In simple language NF-kappaB is a collection of proteins that can profoundly affect the transcription of DNA, that is the production of messenger RNA and the subsequent productions of proteins encoded by DNA.  It can target over 200 human genes in different kinds of cells.  It has positive roles in maintaining health and also can create disease conditions and accelerate aging.

According to a key study, the gene sequence motif most closely associated with aging is that of NF-KappaB.   “NF-kappaB is found in essentially all cell types and is involved in activation of an exceptionally large number of genes in response to infections, inflammation, and other stressful situations requiring rapid reprogramming of gene expression(ref). It is a very rapidly-acting substance, a “first responder” to harmful cellular stimuli.  NF-kappB tends to be plentiful in cells of older people. 

Normally, NF-kappaB lives in the cytoplasm of cells where it is bound up and kept out of the nucleus by a family of substances called IkB (inhibitor of kappaB).  When a harmful extracellular stimulus is perceived, the IkB inhibitor molecules are modified by a process called ubiquitination and destroyed by cellular processes known as proteolysis(ref).  The result is that the NF-kappaB is freed to translocate into the nucleus where it can bind to a variety of genes, activate them and produce a variety of impacts including vicious pro-inflammatory ones.  These processes are in fact quite complex involving many proteins, adapter, promoter and co-activator factors.

“Recently, considerable progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1(ref).”   NF-kappaB plays a wide variety of roles going far beyond control of inflammation.  The aging process appears to involve changes in immune regulation and, among other things, NF-kappaB appears to be the master regulator of both the adaptive and the innate immune systems(ref). 

There is a large amount of research going on, basically focused on how inhibiting the expression of NF-kappaB can be used to prevent or control cancers, cardiovascular diseases and other inflammatory-related disease processes.  On a molecular level, there seems to be three possible strategies: 1 prevent the unbinding of NF-kappaB from IkB, 2, inhibit the translocation of NF-kappaB into the nucleus of cells, and 3.  prevent the activated NF-kappaB from binding onto and activating genes.  In a previous post I described an important experimental substance DHMEQ which acts through the second approach to inhibit the expression of NF-kappaB.  The third approach generally involves histone deacetylation.  That is, it involves coiling up the DNA in the neighborhood of genes so that those genes are not accessible for activation by the NF-kappaB. This appears to be the main mechanism used by curcumin, resveratrol and other dietary polyphenols for inhibition of gene activation by NF-kappaB(ref). 

I remind my reader that 39 of the supplements in my Anti-Aging Firewalls regimen are inhibitors of NF-kappaB expression.  Most of them work through this third mechanism.

One key challenge is finding therapeutic interventions that distinguish between the component NF-kappaB transcription factors: p50, p52, p65 (RelA), c-Rel, and RelB.  The research literature related to NF-kappaB is rapidly growing and increasingly difficult to follow.  A recent and excellent review and synthesis article can be found here.

The title of this post does not suggest a very noble undertaking. If a fruit fly has Parkinson’s- like shakes, so be it.  Who should care about the health of these pesky creatures and why?  A study reported in the May edition of Cell Metabolism suggests the answer.  The researchers introduced a gene called AOX into fruit flies (drosophila melanogaster), a gene that is found in a number of primitive species but not fruit flies, humans or other vertebrates for that matter.  We have lost the gene over the course of our evolutionary history.  The AOX gene reduced the number of free radicals and free radical damage in the mitochondria of the fruit flies, alleviated their Parkinson-like symptoms, and protected the flys from cyanide and other toxins.  There seemed to be no negative side effects to introducing the gene.   The gene affects mitochondrial electron chain transfer.  It “in essence acts as a bypass for blockages in the so-called oxidative phosphorylation (OXPHOS) cytochrome chain in mitochondria, ” a chain central to energy metabolism (ref)  That chain involves hundreds of proteins and complex interactions, but it appears that this single gene can significantly affect the whole chain.  The researchers had previously inserted the AOX gene into individual human cells and established that it found its way into the mitochondria where it was stress-protective.  The current study establishes the protectiveness of AOX for a whole organism – the fruit fly.  AOX is known to be related to longevity in some lower species.  If the approach worked for humans – restoring a historical gene to the genome that was deleted in the course of evolutionary history – benefits in both treating mitochondrial-related diseases and life extension might be realized.  Of course, experimentation must be done with caution.  The gene would have to be taken from the DNA of some lower species before it is inserted into human DNA.  Remember the horror-thriller B movie The Fly?

It has long been known that females tend to outlive males.  I have only to look at my own family’s history to see how that kept happening.  And apparently this also happens in a variety of other species as well. People have asked me “why?”  The best explanation seems to have to do with hormones and our old friends: longevity genes, antioxidants and mitochondria.  In this paper, the Spanish authors trace the phenomenon to “the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males.”  Looking at rats, “Oxidative damage to mitochondrial DNA in males is 4-fold higher than that in females(ref).”  Also see ref.  Estrogens are not particularly good for males.  However, I speculate we males might get some of the same longevity benefits by taking anti-oxidant combinations that strongly affect the mitochondria, like Co Q-10, actyl-l-carnitine and alpha-lipoic acid(ref).

Previous studies have found that women who have babies naturally in their 40s or 50s tend to live significantly longer than other women. At first it seemed that epigenetic factors were at work here.  The theory was that something changes in the DNA of women who give birth late in life leading them to live longer.  However, a new study reported today indicates that brothers of women who gave birth late in life also lived longer, but their brothers’ wives did not.  “Brothers who had at least three sisters, including at least one sister who gave birth at age 45 or later, were 20 percent to 22 percent less likely to die during any year after age 50 than brothers who had no “late fertile” sisters.(ref)”  Moreover,the wives of the brothers lived normal life spans.  This suggests that familial genes were a major factor enabling women both to give birth later in life and to live longer as their brothers did, suggesting that the same genes prolong both lifespan and female fertility.

The study is based on examination of  birth and death data from two disparate historical databases, a genealogical records database at the University of Utah comprising records of 1.6 million Utah Mormons, and  a database at the University of Montreal’s Program on Demographic History Research, which has records on 400,000 people who lived in Quebec between 1608 and 1850, mainly Catholics.  The strong religious influences in both populations encouraged large families, and led to some women giving birth in their 40s and 50s. Modern birth control was rarely practiced.

The study’s main author, demographer Ken R. Smith, a professor of family and consumer studies at the University of Utah. Said “If women in your family give birth at older ages, you may well have a chance of living longer than you would otherwise.” “If you have a female relative who had children after age 45, then there appears to be some genetic benefit in your family that will enhance your longevity”.  Further, “The new thing here is what most evolutionary biologists long have argued: that survival and reproduction are intrinsically linked to one another. So the novel finding in this paper is discovering this link in humans before modern contraception.(ref)”

The answer depends on the study.  As far back as 1997, epidemiological studies suggested that moderate regular consumption of wine, red wine in particular, was associated with decreased risk of ischemic heart disease death(ref).   Then there is the often-cited 2007 study done by researchers at Wageningen University in the Netherlands of 1373 men born between 1900 and 1920(ref).  That study showed that, compared with men who did not consume alcoholic beverages, wine drinkers lived an average 3.8 years longer. Dr. Daan Kromhout, a senior author of the the study and vice president of the Health Council of The Netherlands is reported to have said “– men who drank about a half a glass of wine a day had a 40% reduction in all cause mortality and a 48% lower incidence of cardiovascular death.” 

On the other hand, it appears that women who drink just one small glass of wine a day significantly increase their risk of getting a number of cancers.  This is according to an article in the Feb 24, 2009 issue of the Journal of the National Cancer Institute reporting on a study of 1,280,296 middle-aged women conducted at the University of Oxford in the UK.  Of the women who drank, the average intake was the equivalent to a small glass of wine or 8g of alcohol. Drinking is estimated to result in 7,000 additional cancer deaths a year in the UK, 15 extra cases of cancer per 1,000 women(ref).  Rates of breast, oral, rectal, oesophageal, laryngeal and liver cancer were higher in the wine-drinking group.   “In an editorial published alongside the research, Michael Lauer and Paul Sorlie at the National Heart, Lung and Blood Institute in Maryland, US, write: ‘From the standpoint of cancer risk the message of this report could not be clearer. There is no level of alcohol consumption that can be considered safe.’” 

So what is going on here?  Is drinking a little red wine daily very good for the longevity of Dutch men but quite bad for British women?  Is there a critical health difference between drinking a half-glass and a full glass?  If Dutch men can be equated with British women, do the two studies taken together say the cardiovascular benefit of drinking the daily shot of wine exceeds the increased cancer risk?  Or should the British study be paid more attention to because of its much larger population sample?  Or perhaps the Dutch gentlemen were drinking better organic wines than cheaper stuff the English ladies were drinking.  Were the English ladies possibly imbibing wines with carcinogenic contaminants or additives?  Grapes can absorb pesticides and arsenic from the soil and wine can be contaminated by ochratoxin, or aflatoxin, all of which promote cancers.  It is enough to get me dizzy without drinking any wine at all. 

Personally, I might  drink a half-glass of red wine once or twice a month.  However, I take trans-resveratrol capsules twice daily without fail. 

Major future leaps in longevity will most likely result from developments in molecular biology and genomics.  And, on a practical level individual DNA testing will sooner or later play a major role simply because our genomes are different. 

After several years of nothing much happening, individual DNA testing is slowly entering the mainstream. On the medical side, applications include diagnosis of disease susceptibilities, tissue typing for organ transplantation, prenatal genetic assessment, assessments in cardiology and oncology, and screening for infectious diseases. On the consumer side, popular applications include paternity testing and testing for HIV; such tests are sold via Internet. And of course there are niche markets such as in forensics.  The cost-effectiveness of DNA testing is rapidly improving as is the range of applications, and within a five-year period. Individual DNA testing will probably have expanded by an order or two of magnitude.  According to an article in GEN, “The Sky Could Be The Limit For DNA Testing.” 

The traditional technology for DNA testing uses a technique called PCR standing for polymerase chain reaction.  PCR is a technique used to multiply one or a few pieces of DNA in a couple of hours into millions or more copies.  It works even when the source DNA is of relatively poor quality and it has become one of the most widely used laboratory techniques in molecular biology. Plain PCR is a labor-intensive multistep process that can be done for specific screening purpose in a lab but not in an ordinary kitchen.  Some companies, Roche Molecular diagnostics in particular, have developed technological “platforms” which automate the major steps of PCR.  For example “The COBAS® AMPLICOR Analyzer is the first benchtop system to fully automate the amplification and detection steps of the Polymerase Chain Reaction (PCR) testing process on a single instrument. It combines five instruments into one (thermal cycler, automatic pipettor, incubator, washer and reader).”  A number of other platforms for DNA amplification and molecular testing are being developed.  They include microarrays, beadarrays, and electrochemical arrays and may some day displace PCR.  Their cost-effectiveness and user-friendliness continue to improve.  But so far PCR remains the main technology with Roch Molecular Diagnostics enjoying by far the biggest slice of the market. 

As time moves on and the diagnostic processes become simpler and less expensive, more and more medical labs are acquiring molecular diagnostic capabilities.  Short-term driving forces include lower cost and simpler test units, units capable of doing multiple kinds of tests, and desire for faster turnaround time than possible if the tests have to be outsources. Today, in the infectious disease and oncology areas, traditional biochemical testing still is the dominant mode, with molecular testing representing only 20%-30% of the market, but the molecular/genetic testing continues to gain market share. 

In the news and frequently reported  in this Blog, there is a steady stream of research reports linking diseases to genes and gene polymorphisms and indicating new molecular therapy targets.  There is an accelerating need for individual genetic testing if the fruits of such research are to be harvested.  A longer-term driving force for widespread adoption of individual DNA testing is the slow emergence of personalized molecular-based medicine for assessing disease susceptibilities, disease detection, disease course prognosis, and prediction of patient drug response.  I think this shift in paradigm may require 20 or more years before it is firmly in the forefront.  Clearly this paradigm shift will have a major impact on protecting the health and extending the lives of those who will benefit from it. 

Of course there are other segments of DNA analysis besides tests designed to helped individuals.  There has been enormous progress in development of automated technologies for analyzing entire genomes.  An example is Affymetrix’s microarray-based Gene Titan  system. 

Molecular laboratory testing is already a big business.  The Gen article quotes a source (Kalorama) indicating estimating the 2007 worldwide market for molecular assays to be $3.7 billion.   The market is projected to grow at an 11% annual rate, reaching $6.2 billion in 2012.  Certain segments of this market are expected to grow at much higher rates.   The highest-growth areas of DNA testing according to the GEN article are pharmacogenomics (35%), inherited disease testing (25%), oncology and infectious diseases. 

In previous postings I have compared the rate of progress in the computer field in 1956 with the rate of progress in genomics and longevity science today.  Personalized diagnostic testing today is playing a transformative role today in medicine as developments in computer memories did back then.  Both then and today, scientific and commercial developments strongly supported each other.  It will be a while before we have the analog of the PC revolution, however, when everyone does their own DNA testing in their homes using inexpensive kits.  I fully expect this to happen within 20 years or so, however.

I have mentioned the P53 tumor-suppressor gene a number of times in my Anti-Aging Firewalls treatise, for example pointing out that  “Resveratrol and curcumin activate the P53 gene in many strains of cancer cells, leading them to commit apoptosis.”  Today’s news revealed new research findings regarding normal P53 genes and mutant P53 genes found in cancers. 

First, how cruciferous vegetables work to defeat cancer 

It has long been bandied about in alternative health circles that cruciferous vegetables like cabbage, watercress and broccoli tend to be cancer-preventative.  But why this was so remained a mystery.  A recent research report lends light on this mystery, indicating what might be the main biomolecular mechanism involved.  These foods contain phenethyl isothiocyante (PEITC), a natural phytochemical.   P53’s usual job is to stop a defective cell, one with DNA damage or expressing oncogenes, from dividing and possibly force the cell to kill itself. However, in many cancers the P53 gene is mutated and does not do that job.  Instead, the mutated P53 allows the cancer to develop and spread.  The reported research indicates that PEITC has a capability to selectively deplete mutant p53 leading to restoration of the wild type (normal) p53.  In effect the P53 checkpoints against the cancer are restored by the PEITC phytosubstance.  The press release concludes “This novel finding suggests that the PEITC and other compounds in the isothiocyante family could play important role in both cancer prevention and treatment of human cancers with mutant p53.” 

Second, certain efforts to protect cancer-fighting P53 can backfire and also protect mutant cancer-promoting P53 

News on a research report in the in the current issue of the journal Genes and Development points out a danger of trying to restore P53 function in a patient’s tumor without knowing what kind of P53 is involved, wild type or mutant.  If the P53 is wild type, restoring its function could help zap the tumor.  If mutant P53 is involved, however, the result could be the tumor thriving and spreading.  “The importance of this study cannot be overemphasized,” the researchers concluded. Drugs that try to protect normal p53 by inhibiting the p53-degrading protein Mdm2 also would protect mutant p53 “with dire consequences.”   

Taken together, the two studies point out the high relevance of phytochemicals like PEITC for P53 treatments of cancers – because they act differentially against mutated P53 and promote the restoration of wild-type P53.  They can tell the difference between the bad guys and the good guys.  P53 activation that can’t tell the difference is potentially dangerous.