Overexpression of the DNA Repair Gene PRP19 is Shown to Modestly Extend Life in Female Flies

Genetic and other interventions that extend life span in only one gender of a laboratory species seem not to involve large effects, judging from those discovered to date. In this example, a gene known to be involved in DNA repair is found to decline with age in a more pronounced way in female flies. In turn, enhanced levels of the protein produced from this gene extend only female median life span in flies, by something like 10-25% according to the data presented in this paper. This isn't all that large an effect in the grand scheme of things; short-lived species have a far greater plasticity of life span in response to environment and genetic alterations, and researchers have produced far larger gains than this in flies using methods that are known to produce very little effect on life expectancy in humans.

This is the way things tend to work: members of longer lived species have life spans that are relatively unresponsive to environmental influences and single gene alterations that produce quite large changes in the life spans of flies, worms, and mice. These interventions are are all based on producing altered states of metabolism capable of slowing down the pace of aging in some way, however. They are a slowing of the accumulation of damage, without any attempt to repair that damage. There is as yet no data on how the other approach to the problem, actually repairing that cell and tissue damage in order to produce rejuvenation, will differ between short-lived and long-lived species. This will arrive in the years ahead; there is life span data now for senescent cell clearance in mice, and something like a five year study of efficient senolytic treatments in old humans should provide enough data to estimate the effects on human life span.

According to the disposability hypothesis of aging, functional decline results from the accumulation of stochastic damage, for example, due to somatic mutations, and is counteracted by investment into somatic maintenance and repair. Accumulation of DNA damage due to decreased repair can accelerate aging, as is observed in progeroid syndromes in humans and mouse models. Similarly, increased exposure to DNA damaging agents, for instance during chemotherapy, can lead to a phenotype of acquired premature progeroid syndrome. Accelerated accumulation of DNA damage and premature aging phenotypes are typically well correlated, but whether improved DNA damage repair (DDR) can extend organismal life span remains largely unclear.

In the fruit fly (Drosophila melanogaster), a well-studied model for dissecting the mechanisms of aging, spontaneous somatic mutations accumulate with age, and defective DNA repair is associated with reduced life span. However, overexpression of DNA repair factors in the fly seems to have highly variable, sometimes contradictory effects that depend on sex, developmental stage, and the tissue of intervention. For instance, PARP-1 modifies histones, transcription factors and repair enzymes in response to DNA breaks, and its endogenous activity is well correlated with life span in several mammalian species. In Drosophila, overexpression of PARP-1 prolongs life span in both sexes, yet only when restricted to the adult nervous system. Similarly, overexpression of Gadd45, a regulator of DNA repair and cellular stress responses, in the nervous system increases fly life span but ubiquitous expression is lethal. Thus DNA repair factors can affect Drosophila life span and stress resistance either positively or negatively, depending on the sex and on whether overexpression is ubiquitous or limited to the nervous system. Interestingly, all repair factors that were expressed throughout the adult fly body were found to shorten life span.

Here, we examine the role of adult-specific overexpression of the DNA repair factor Prp19 in affecting life span, stress resistance, and DNA damage in Drosophila. Biochemically, PRP19 interacts with multiple players in the DNA repair pathways. Apart from its role in the DNA damage response, an intriguing aspect of PRP19 function is its concomitant and essential involvement in co-transcriptional splicing, where the PRP19 complex regulates the rearrangement of the spliceosome.

In support of a role for PRP19 in the aging process, it has previously been shown that decreased levels of PRP19 accelerate the induction of cellular senescence in mouse embryonic fibroblasts, reduce self renewal of mouse hematopoietic stem cells, increase UV-A-induced skin aging in mice and decrease differentiation of human adipose-derived stromal cells. Conversely, increased levels of PRP19 extend the replicative potential and total life span of cultured human endothelial cells. However, the role of PRP19 in organismal life span is unknown. Here, we show that ubiquitous overexpression of the Drosophila ortholog of PRP19, dPrp19, reduces DNA damage and extends organismal life span of adult female flies. Our results suggest that PRP19 plays an evolutionarily conserved role in the DNA damage response, aging, and stress resistance.

Link: https://doi.org/10.1038/s41514-017-0005-z

Comments

"This will arrive in the years ahead; there is life span data now for senescent cell clearance in mice, and something like a five year study of efficient senolytic treatments in old humans should provide enough data to estimate the effects on human life span. "

On one hand senescent cells seem to drive a lot of diseases or at least when you study their effects on mice that is the conclusion.

On the other hand, once you remove them their place will be taken by cells from the same diseased organ.

It's hard to say whether or not it will have any detectable effect on human lifespan. Out of all the therapies Aubrey has promoted I feel like this one is the worst when it comes to possible lifespan benefits, though it might have a very visible effect on health if we are lucky.

Posted by: Anonymoose at July 4th, 2017 9:02 AM

Let me share a little theory I've been building for a while.

If you look at the last couple of months in basic science done on senescent cells you get papers like these ones:

http://www.tandfonline.com/doi/abs/10.1080/15384101.2017.1339850?journalCode=kccy20

http://journal.frontiersin.org/article/10.3389/fimmu.2016.00445/full#h1

Which leads me to one conclusion:

Clearing senescent cells is indeed beneficial but more importantly inducing a higher cellular turnover might be what is actually conferring most of the benefits - the soma of old animals is damaged. Whether the cells are senescent or not is irrelevant at that point, your only hope for regeneration is forcing the stem cell populations to work overtime.

Of course having a receptive environment is important so removing the senescent cells is valid. But there is strong evidence most of the benefits we are seeing are in no small part the result of non-precise methods of removal - neither quercetin, nor dasatinib seem to be all that senescent cell targeting. Heck quercetin seem to simply induce higher rates of apoptosis and that's about all it does regardless of the cells present.

Ironically enough this quest for better targeting might be in vain, or indeed - counterproductive.

Posted by: Anonymoose at July 4th, 2017 9:26 AM

@Reason p16 is one of the reasons why I started thinking about this. I remembered an "old" paper from a bit after the paper with the first mice engineered to kill their senescent cells was published. I think it was by MayoC and it was about immune cells expressing p16, and back then the Mayo researchers or whoever wrote it was adamant those cells are not senescent (at least not in the classical sense).

And recently we started getting papers like the 2 I posted - p16 expressing cells are not always senescent, says the first and the other is with yet another type of immune cells previously considered senescent. And It made me think - are we really killing senescent cells, or just old cells in general?

Maybe we need to extend the definition of senescent cell, or maybe we're simply killing old cells, or maybe both are one and the same - maybe most if not all cells from old mammals display some level of senescence.

There's quite a bit of ground for basic research here but I'm not sure anyone would bother doing it. Not in a hurry.

Posted by: Anonymoose at July 4th, 2017 10:22 AM

There is more potential in gene therapy than this, but you have to get a lot better. Single gene alterations are pathetic, and won't produce any significant effect ever. My guess is you'd have to do it on hundreds of genes at the same time in different tissues, and no one is up to it. It's not easy to know which direction to go, and I agree it's easier for now to just repair the damage like SENS. My dream though is that at some point it will be possible to change genes in such a way that the body is a perfect self-maintaining machine with no or only minor repairs necessary. Dreams? Maybe, but who knows what would be possible.

Posted by: K. at July 4th, 2017 1:16 PM

Hi !

Just a 2 cent.

I believe that the senescent cell numbers are relatively low for the whole life (although do increase more during the very last moments, massive senescence can happen in one or more organs just like it does in spontaneous senescence causing diseases).

I think it's because there is the general term senescence but there is specifity to it; you have three 'main' types of senescence; oncolytic, replicative and spontaneous. I'm sure there are even others and they have not been found yet.

Oncolytic senescence is dependent on cancer signals that alter the mTOR regulated senescence entry - which alters p53/p16/p21 inflammatory gene tumor suppressors that are increased to counter the tumors - at the cost of accelerated aging by excess ROS production from p53/p16 (cancer invasion/metastasizing is an Accelerated Epigenetic aging inside body. Plus cancer cells display accelerated epigenetic aging (for they are under p53/p16 ROS attack) - Until, it stabilizes and they can become immortal; while, the other healthy cells surrounding them display accelerated epigenetic aging because of the immense oxidative stress they are getting from said activation of tumor suppressors genes (p53/p16/p21)). They are not immune to the mega ROS production meant to 'counter' the tumors/destroy them. This type of senescence is different than all others.

Replicative Senescence : Aging (especially centenarians whom lasted 'healthy enough' to tough it to a 100+) is accompanied by many cell cycles over time/passage/replication over time. The Hayflick limit creates an additional limit/barrier on human lifespan for it stops somatic cell cycle/replication once the cell has 'used up' all its 'rounds' of replications (especially in somatic non-dividing long-lived/post-mitotic ones like neurons and nerve ones) : that is regulated by the Telomeric DNA counting mechanism; shorter telomeres means that pretty soon the 'clock' will be over and out for the 'cell cycling' (cell cycle arrest - and mTOR geroconversion to Senescence after cell cycle arrest). Then, it will Replicative Senescence entry. These cells are different and have a different Epigenetic Signature/phenotype; they are 'Aged' (over large amount of time) in the 'intrinsic' way (when we think of 'healthy aging' until you die, that is it). I believe that the amount of senescent cells is kept mostly low for the entire lifespan of the animal; because of the incompatibility with lifespan. As such, there are different types of 'states/phenotypes/signatures' for different types of cells; most cells in a younger human are not old, they are in a majority kept young and devoid of senescence. Senescence mostly starts happening in 60-70-80s decades...and when I say senescence, I mean all three pathways but they can happen sooner in young life (As I experienced when I had atherosclerosis/angina/still have it (and I'm young)). Replicative senescence is for the older animals whom reach the full life. While oncolytic and spontaneous are for all walks of age.

Spontaneous Senescence : This a state of oxidative stress causing spontaneous senescence : the 'health' threshold is being broken - in any age of an animal. This could be a baby, a teenager, a mid-adult or a centenarian elder. This 'health' threshold state must be 'kept', if it goes below that threshold - spontaneous senescence happens (at any time in life). This, directly, targets 'the health' of the animal - and is separate thing from intrinsic aging (Health and Intrinsic Aging share common mechanism but have their distinctions (such epigenetic clock and many pathways that make it 'differ' and be something else that simple 'Senescence' umbrella term - there is much more Specificity to it than we know); one is a threshold 'in the moment' (health) while the other is a threshold 'over time/years' (lifeyears)).

In any case, it would be incredible to have a self-maintaining body and thus, never age (for now a pipe dream) but it could happen - I just think that the problems will come sooner than later; but we're ready; we did go on the moon. A couple of the SENS therapies and others that are coming have potential for sure (we said many times I feel like a parrot; but, for this, we have to BE PARROTS so people get the d*mn message and it gets in their heads that we're not going anywhere and death must be Cured as absurd-sounding as it sounds; f...the 'correctness' and make it happenl they will thank us LATER when they are actually (still) ALIVE rather than dead). IT makes me think of the parents that say NO to the Doctor to pull the plug on a child that is on the 'machine' from a coma...doctors will say there is nothing to do anymore and you must pull the plug - Accept it and let your child go...then I think, I understand that sometimes we must accept defeat and capitulate. But, on this, I think we really should not backdown so easily, this is our life we are talking about OUR SINGLE ONE AND ONLY and then it's Death FORRRREVERR. Yaeh long like that. It'S TER-MI-NAL, more terminal than TERMINATOR himself.
kidding...Some parents they said no don'T pull the plug Yet...and what do you know, that child was SAVED by 'some' 'miracle'...the child 'woke up' from his/her coma some 6 months later...and he/she Lived On...what would have happened if they had 'given up' of their child and pulled the plug...

Just my 2 cents.

Posted by: CANanonymity at July 4th, 2017 2:04 PM

Hi CANanonymity - I think your three types of senescence are really the same thing (or very similar):

Replicative senescence is built into all proliferating human cells and these arrest and senesce when the telomeres get too short - they are then replaced from stem cell sources, until these too senesce (why is not yet clear);

Oncolytic Senescence is simply caused by DNA damage that is not repaired (can happen even with long telomeres but is less likely, hence rise in cancer with age);

Spontaneous Senescence is similar to Oncolytic, it is due to some damage - either external (UV, poison, injury) or internal damage from other cells(senescent or cancerous). The one question mark is whether Blagosklonny is right and non-dividing/non-aging cells that are held in check can also senesce if MTOR signal is excessive, even with long telomeres - probably down to be filled up with the protein that precedes the aborted cell division. I expect this wouldn't be that significant but might explain how Stem Cells senesce.

And of course any kind of damage such as that causing your spontaneous and oncolytic senescence use up extra replicative rounds and hence shorten the time till you hit the replicative senescence barrier!

As for the prospects for senescent cell clearance, almost certainly there will be healthspan benefits as so many cell pathways end up here (providing it doesn't kill the very old who don't have any spare replicative rounds to replace ablated cells), but we still have to address 'The Daddy' - replicative senescence, so I suspect there will be no max lifespan extension.

Posted by: Mark at July 5th, 2017 6:01 AM

Hi Mark ! Thank you for your response.

It's true that these pathways share much common mechanism and are pretty much the same, though they do have different purposes (oncolytic (destroy tumor formation), replicative (limit maximum life of animal) and spontaneous (limit amount 'limit' of damage (health) animal can take while living; which would cause oncolytic senescence at some point when cells would become rogue from oxidative stress. Oncolytic senescence is also more than DNA damage, it is also genetically acquired and unacquired mutations (spontaenous themselves too) that do not necessarily show DNA damage but show rearrangement of Nucleotide position/combination/errors)). But, in majority, yes, cancer is mostly an inflammation problem caused by oxidative and non-oxidative stress pathways (UV rays (which cause spontaenous senescence - but also skin cancer oncolytic senescence - these types of senescence are very close and 'woven' together, like shift-shaping-changing and it can turn from one to the other in a few 'signals'.),

''And of course any kind of damage such as that causing your spontaneous and oncolytic senescence use up extra replicative rounds and hence shorten the time till you hit the replicative senescence barrier!''

There is much ambiguity there (I think), it is understood that DNA damage and oxidative stress in those diseases accelerates how quick replicative senescence comes - but there are nuances there I think. What I'm trying to say is that (why I believe they are seperate (yet entwined)) replicative senescence is dependent of cell cycling counting mechanism of telomeres in chromosomes; damage can be repaired (and it is, continuously through mismatch repair (MMR), ribonucleotide excision repair (RER), nucleotide excision repair (NER) and base excision repair (BER)...). I'm thinking that damages are not sufficient to reduce telomeres all that much (we have to remember telomerase is activated in nearly all cells (even in ones we thought there was no telomerase, it might be very seldom 'telomerase' bursts but they happen just to undetectable levels), its job is to counter telomere shortening (when you experience oxidative stress)). In fact, some studies showed an Elongation of telomeres over time (in some cases) while in general, telomeres shrink at a pretty constant speed (and telomerase is Helping to keep that telomere shortening rate stable; if you take it away telomeres will accelerate in loss. Telomerase has triple role or more : lengthen telomeres, cap telomeres/increase stability, reduced ROS emission/protect against oxidative stress)). I'm not saying that damage don't accelerate replicative senescence, most (if all) of them do; I'm just trying to see how much of an impact they have : if they don't affect telomeres all that much (and they do affect telomeres (UVs exposure for example accelerate skin fibroblast telomere loss), then it would mean that no; they don'T affect replicative senescence as much as what we would think; for replicative senescence is dependent of telomere dynamics. What is certain is that they are Damaging -but that (some) damage can be nullified or repaired by the body's cell DNA nucleotide repair systems and telomere systems.

''Replicative senescence is built into all proliferating human cells and these arrest and senesce when the telomeres get too short - they are then replaced from stem cell sources, until these too senesce (why is not yet clear);''

I think it is due to the same problem, stem cells are bound by replicative senescence too.
They have telomere dynamics that are the same as other regular cells. That is, they lack 'enough' telomerase to count telomere shortening Completely and thus, stop negative loss of telomeres (whether in somatic cells or stem cells). The only exception to that rule are the Immortal-like stem cells (whom, unsurprisingly) use Telomerase (sufficiently to completely counter telomere loss and keep a Positive (frozen/rising) Telomere Length always) to be replicatively immortal (primordial germ cell/gonadal stem cell).

''The one question mark is whether Blagosklonny is right and non-dividing/non-aging cells that are held in check can also senesce if MTOR signal is excessive, even with long telomeres - probably down to be filled up with the protein that precedes the aborted cell division. I expect this wouldn't be that significant but might explain how Stem Cells senesce.''

Same here, can'T say, but I believe that would be quite true - mTOR is a double-edge sword to any cell - even ones with long telomeres (it's why spontaneous senescence happens, these are not always TElomeric-dependent signals but independent-signals. Cell cycle arrest can happen short, medium or Long telomeres; makes no difference, the signal is what makes the difference).
It's a bit like p53p16 genes that are 'bad' (supposedly), but, in fact, are good for they counter tumors (through inflammating/damaging cancer cells until they senesce - too); these genes are 'two-faced' - in one situation they act 'nice' and in another 'scenario' they become lethal. This a clear sign that the body is a pure finite intricate 'balanced' Balance with 'forward/back-at-you signals' 'negative/positive-FeedBack Mechanisms' that you can't mess (too much) in or cause havoc (it's the Yin and Yan sign to the extremest degree). Evolution made us as a 'balance' (that it refined and optimized over time and over millions of genes, we playing in it can mess things up (of course); but, if we wish to reverse aging we have no choice but 'to mess things up').

''As for the prospects for senescent cell clearance, almost certainly there will be healthspan benefits as so many cell pathways end up here (providing it doesn't kill the very old who don't have any spare replicative rounds to replace ablated cells), but we still have to address 'The Daddy' - replicative senescence, so I suspect there will be no max lifespan extension.''

Exactly, me too, I believe there will be health benefit for sure (since what small amount of senescent cells we ahve can wreak havoc; it's so hypersenstive; so removing them would have a dramatic impact and increase our Stem Cells capability to rebuild tissues - thus, improve health(span). Though, I do say, Health - not Maximum lifespan (not by much at least) because of Replicative senescence).

Yes, replicative senescence, that's the one. I'm too of the opinion that is a barrier that will be hard to get over...how you do stop a 'normal' process like that..over the years...the only way is to slow down the 'time to completion of 1 round', which means removing damages and keeping a perfect redox (since damages depend on redox (un)availability), rejuvenation could somehow circumvent that problem (like replacing the 'used' parts of the old car analogy, but doubt it's that simple):

Animals that live 500 years face the same problems, Replicative senescence - yet they live 500 years. For example, red lobsters whom can live 150 years and have active telomerase in their tissues (unsurprisingly; telomerase twarths replicative senescence by accumulating too many short-length telomeres towards the end of a lengthy lifespan, hence they live 150; telomerase doesn't just stop telomere shortening, it stops oxidative stress that accelerates aging, it increase Maximum Lifespan by increase the replicative potential from Taller Telomeres (thus more Rounds of cell cycling available - the instant the telomeres rise).

Animals such as a bowhead whale (200 years) or a greeland shark (500 years) tells us that protracted growth is a key determinant (mTOR is behind this), slow sexual maturation and developmental growth (which alter cell cycle dynamics and thus, replicative senesnce). These animals maintain pristine health but have slower metabolism combined will nearly null damage - to telomeres - and have enough telomerase to counter any (possible); thus no real Net Loss of telomere - only Gain. I have a fear that telomere-replicative senescence problem may be something we have difficulty getting over (it could end up being the 'last' barrier that makes us 'cap' at 122 or so, that's it), since we depend on it so much (if we live healthily and, from it, we die after the full life when we reach pseudo human MLSP (maximum lifespan)).

Just a 2 cent.

Posted by: CANanonymity at July 5th, 2017 4:33 PM

Hi CANanonymity!

'replicative senescence is dependent of cell cycling counting mechanism of telomeres in chromosomes; damage can be repaired (and it is, continuously through mismatch repair (MMR), ribonucleotide excision repair (RER), nucleotide excision repair (NER) and base excision repair (BER)...). '

Your knowledge of DNA repair mechanisms is very impressive, any good books/articles I could read to get up to speed on this?

'Yes, replicative senescence, that's the one. I'm too of the opinion that is a barrier that will be hard to get over...how you do stop a 'normal' process like that..over the years...the only way is to slow down the 'time to completion of 1 round'

This is what Blagosklonny writes about mostly, using Rapamycin to slow down the time for 1 replicative round (by temporarily blocking the protein synthesis required before cell mitosis) - therefore we have the chance to develop at normal human speed, but then slow MTOR down in adulthood. Of course do it too much and the fastest replicating tissues (such as immune cells) cannot do their job - hence rapamycin is used at higher doses as a immunosuppressor.

I also think AAV TERT treatments are a way forward to beat the replicative limit; Michael Fossel is talking about doing a clinical trial injecting it via epidural to treat Alzheimer's (presumably he is aiming at astrocytes with short telomeres).

Posted by: Mark at July 6th, 2017 3:20 AM

Thanks Mark, you too your knowledge is also very impressive (I'm no researcher just a visitor intrigued and learned (some) biogerontology (also I had/have a deadly disease (Atherosclerosis in a young age (I obtained French Canadian Hypercholesteremia genetic mutation (backtraceable to France (founder) ancestral mutation source)), it made me 'Awaken' or I was going to die of it (on top of the the fact my mother died of stomach cancer at 56 years old (thank god my grand-mother lived to 92, that's gives a glimpse of hope (but, I'm feeling I won't even reach that; she had perfect health (I don't, so it's not looking too good..sigh))!

Incredible stuff (AAV) I can't wait to see how it turns out (I hope that it could somehow how, Liz Parrish Bioviva did extend her telomeres (but telomerase can destabilize the chromosomes when in excess); but we don't know yet the implications of this - she is biologically younger, but there has been nearly zero studying her after her self-experiment). Of course, this is in direct contradiction to SENS, whom intends on stopping telomerase altogether (to stop cancer formation from high-jacking telomerase for themselves to lengthen their telomeres (Although, they can circumvent that with ALT (alternate lenghtening of telomeres) process; but, many, would succumb upon telomerase abolition/telomere lengthening blocking in cancer cells - they are after all, in the low 2kb region (most of them) as such, it's not very hard to finish them off (for the ones 'hanging' in the the low-telomere lengths)); but then, we still have the problem of replicative senescence (the SENS answer is damage repair so that replicative senescence doesn't happen; I hope it'S true but I doubt that would be it, because Hayflick limit (end-replication problem) replicative senescence ontinues its course merry along, damages or not;)

Just a 2 cent.

Posted by: CANanonymity at July 6th, 2017 12:33 PM

Hi CANanonymity.

I find it very interesting how people came to be interested in life extension. I wish you luck in counter acting atherosclerosis and living a long time (long enough to benefit from whatever treatments come along).

I myself got interested in LE when my mum died in her 60s very unexpectedly from Cancer. I started looking into cancer to see if I carried any harmful alleles. I was lucky and I didn't (as far as i could tell). But I then 'woke up' when my reading showed me LE was a real possibility (though far from certain in my lifetime).

As far as what we were talking about technically, I don't think the SENS approach is incompatible with AAV TERT, after all AdG wants to blockade any telomere extension but instead regularly (say every 10 years) add new stem cells with fresh new, long telomeres. Sounds like it could work but like everything in SENS it is belt and braces approach, very thorough but quite hard. AAV TERT might be a nice intermediate treatment.

As for whether removing all damage will make a cell young or not, I suspect it is a bit of both. Long telomeres will probably restore the youth of a cell in most respects, but there is likely to be some undegradable waste that only SENS can deal with. Conversely remove all the waste but don't reset telomeres and you probably still have a dysfunctional cell.

Posted by: Mark at July 7th, 2017 3:18 AM

Thanks again ! You too ! I'm sorry/My condolescences for your loss. Cancer and atherosclerosis all truly the most insidious and common type of diseases. Diabetes just a nudge behind. If we solve this trio of diseases it will have massive impact in humanity (in terms of health in developed and less developed countries), I think SENS is on its way to that for sure. It may even put a dent in the pharmaceutic whom relies on 'sick patients' 'staying sick'.. they will lose money for sure, same thing for hospitals that need their load of patients - there should be No patients in a hospital - if we cure Death and Diseases. The day hospitals are empty and become relics will be something quite 'strange' yet accepted at a certain point (maybe not in our lifetime though, hospitals save lives so much and as such, are there to stay, but in the far(ther) future a paradigm shift could happen; hospitals will not be about 'healing' anymore, but about 'curing death/disease' so that you never need to heal anything or of any disease because you never have any - and you can live extremely longer (indefinite life from reaching LEV or something like that) or nearly as long you wish (1 day or 1 million years - Your Life - Your Call). You could choose when you decide to pull the plug 'on your self/your own life' (when you had enough/lived long enough/done everything/too bored..who knows You Would know it, only you) - while hospitals doctors 'decide' to pull the plug on a patient; that should be your choice. Hospital will dramatically change in the future, it's 100% sure, Biorejuvenation will TRansform humanity (I hope live long enough for that, fingers crossed and but breath not held).

Posted by: CANanonymity at July 8th, 2017 2:44 PM

ADA is a gene affecting telomere length of leucocytes. The rs73598374 CC allele type maintains telomere length by activating telomerase. I happen to have this allele, so it should help preserve my immune system. I checked my DNA for some other longevity genes and found I have the good allele for APOE2, which staves off AD and increases longevity. I also checked my FOXO3A SNP's and found that I am homozygous for the longevity alleles of 12 SNP's that researchers have found confer longevity. Another longevity factor I found is that I have Gilbert's Syndrome, with 2-3X higher levels of bilirubin, a very strong internal antioxidant, that confers a 0.5 all cause mortality benefit on those with the Syndrome. These are just a few of the more important longevity factors I found just by checking my 23andme raw DNA data. Hopefully, geneticists will discover more and more of these longevity SNP's, and then use CRISPR technology to implant the longevity SNP's to people who don't carry them, and also snip out some of the bad SNP's all people carry also.

Posted by: Brian Marcks at July 11th, 2017 2:55 PM

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