Factor X have we finally found the fountain of Youth?

Discuss life, the universe, and everything with other members of this site. Get to know your fellow polywell enthusiasts.

Moderators: tonybarry, MSimon

paperburn1
Posts: 2379
Joined: Fri Jun 19, 2009 5:53 am
Location: Third rock from the sun.

Re: Factor X have we finally found the fountain of Youth?

Postby paperburn1 » Thu Aug 16, 2018 2:36 pm

did not someone on this forum start using this, and what were the perceived results.
https://www.elysiumhealth.com/en-us/basis
Want to know for a friend :D
I am not a nuclear physicist, but play one on the internet.

kurt9
Posts: 549
Joined: Mon Oct 15, 2007 4:14 pm
Location: Portland, Oregon, USA

Re: Factor X have we finally found the fountain of Youth?

Postby kurt9 » Thu Aug 16, 2018 2:49 pm

I've been taking NR (NAD+ regenerator) for the past two years or so. I've not noticed much of a difference. Then again I was feeling just fine (and full of piss an vinegar) prior to starting it. Ask me in another 5 to 10 years.

Given the number of start-ups in the field, it looks like we're within hailing distance of an ageless society.

https://www.nextbigfuture.com/2018/08/e ... ck-on.html

williatw
Posts: 1725
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Tue Aug 21, 2018 11:34 pm

Will the massively rich be able to become massively different? SU Global Summit 2018

Amin Toufani at the SU Global Summit 2018 made several claims and conclusions in regard to the exponential future. One is that 2020-2030 would be remembered historically as the Great Bifurcation. He refers to this as the time when there is not just increasing inequality between the megarich and the rest but when the rich use the wealth to create permanent advantages in lifespan, health, intelligence and other changes.

India’s Caste system has had existed in various forms for 3500 years. This was a system of societal stratification that greatly reduced social mobility and had people marrying people at their same monetary and societal level.

This did result in intelligence breeding and education differences which were handed down through many generations.

Amin point is that exponential technologies will take the differences beyond monetary to buying life extension and cognitive enhancement.



Nextbigfuture tracks these developments and believes those technologies will be developed but they will become as universally accessible as vaccination. However, there will be lags where the best versions will be available to the wealthy first.


Think Brian Wang is being willfully naive here..yes the government might pay for basic longevity treatments even some degree of physical and or cognitive enhancement, but the mega-rich will be able to get the best as soon as it is available; over time the gap between rich and poor will grow probably exponentially as suggested. Imagine what manner of enhancements Mark Zuckerberg's or Jeff Bezos's grandkids would be able to get compared to even the average millionaire; to say nothing of the regular joe/jane (even with government intervention)?




https://www.nextbigfuture.com/2018/08/w ... -2018.html

williatw
Posts: 1725
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Sat Oct 20, 2018 1:32 am

Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression


Abstract

The paramount role of senescent cells in ageing has prompted suggestions that re-expression of telomerase may prevent ageing; a proposition that is predicated on the assumption that senescent cells are the sole cause of ageing. Recently, several DNA methylation-based age estimators (epigenetic clocks) have been developed and they revealed that increased epigenetic age is associated with a host of age-related conditions, and is predictive of lifespan. Employing these clocks to measure epigenetic age in vitro, we interrogated the relationship between epigenetic ageing and telomerase activity. Although hTERT did not induce any perceptible change to the rate of epigenetic ageing, hTERT-expressing cells, which bypassed senescence, continued to age epigenetically. Employment of hTERT mutants revealed that neither telomere synthesis nor immortalisation is necessary for the continued increase in epigenetic age by these cells. Instead, the extension of their lifespan is sufficient to support continued epigenetic ageing of the cell. These characteristics, observed in cells from numerous donors and cell types, reveal epigenetic ageing to be distinct from replicative senescence. Hence, while re-activation of hTERT may stave off physical manifestation of ageing through avoidance of replicative senescence, it would have little impact on epigenetic ageing which continues in spite of telomerase activity.


Although ageing is readily observed at the level of the organism, our understanding of why and how this process occurs has remained speculative until normal human cells were successfully cultured outside the body, where they were found to have a finite capacity to proliferate.

Hayflick estimated that a population of human cells grown ex vivo can double approximately sixty times after which they adopt a permanent state of dormancy termed replicative senescence [1,2]. The cause of this natural limitation to proliferation was eventually found to lie in the “end-replication problem”, which if not addressed by the cell, would lead to telomere attrition at every round of DNA replication [3,4]. It was eventually demonstrated that this does indeed occur and when telomeres shorten to a critical length they trigger cells to adopt the senescent state [5,6]. The identification of telomerase, which replicates telomeres [7,8], and the fact that most adult somatic cells do not produce this enzyme, provided the last major piece of the puzzle that describes the ageing process from events beginning with molecules, proceeding to cells and culminating in the organism. Significantly, this chain of events can be prevented by ectopic expression of hTERT, the catalytic sub-unit of telomerase, which can preserve telomere length and avert senescence of some cells [9,10]. Impressively, these profound insights into the process of human ageing were acquired from careful study of ex vivo cell behaviour.

It was initially thought that the functional and physical deterioration that characterise organismal ageing are a result of insufficient replenishment of cells due to telomere-mediated restriction of cellular proliferation. Senescent cells, which accumulate increasingly in tissues in function of age, were assumed to be passive and merely a consequence of the above-described processes. This notion was short-lived when senescent cells were found to secrete molecules that are detrimental to cells and tissues; a cellular characteristic described as senescence-associated secretory phenotype (SASP) [11–13]. The role of senescent cells in actively causing age-related physical deterioration was elegantly revealed when reversal of ageing phenotype in organs and tissues was observed following the removal of senescent cells in mice [14]. As such, it would follow that if cells were prevented from becoming senescent in the first place, ageing could be avoided. Although there are external instigators such as stress and DNA damage that can also cause cells to become senescent [15], replicative senescence is particular in that it is an intrinsic feature that is part of cellular proliferation and occurs even in an ideal environment. As expression of hTERT has been repeatedly demonstrated to prevent replicative senescence of many different cell types, it is reasonable to consider ectopic expression or re-activation of endogenous hTERT expression as potential means to prevent replicative senescence, delay ageing and improve health [16].

The above proposition would be valid if senescent cells were indeed the only cause of ageing. Relatively recently, an apparently distinct form of ageing, called epigenetic ageing was described (reviewed in [17]). This discovery stems from observations that the methylation states of some specific cytosines that precede guanines (CpGs) in the human genome changed rather reliably and strictly with age [18–22]. This allowed supervised machine learning methods to be applied to DNA methylation data to generate DNA methylation-based age estimators (epigenetic clocks) of epigenetic age, which in the majority of the human population is similar with chronological age [23–27]. The difference between epigenetic age and chronological age, which reflects the rate of epigenetic aging, carries biological significance: increased epigenetic aging is associated with numerous age-related pathologies and conditions [17,28–41]. Conversely, healthy lifestyle and diet is associated with younger epigenetic age [17,42]. Furthermore, epigenetic age can be reversed or reset, as expression of Yamanaka factors in somatic adult cells reset their epigenetic ages to zero [26,43]. Hence, epigenetic age is not merely an alternative means of determining chronological age but is to some degree a measure of biological age or health; a proposition that is further supported by the impressive demonstration that acceleration of epigenetic ageing is associated with increased risk of all-cause mortality [34,39]. Collectively, the descriptions above highlight the fact that epigenetic ageing, in spite of the mathematical origins of its discovery, is not a mathematical contrivance but a genuine ageing process innate in cells.

Several DNAm-based biomarkers have been reported in the literature that differ in terms of their applicability (some were developed for specific tissues such as blood) and their biological interpretation. The pan-tissue epigenetic clock developed by Horvath [26] is applicable to almost all sources of DNA with the exception of sperm. The resulting age estimate by this clock is referred to as epigenetic age or more precisely DNAm age. Although the pan-tissue epigenetic clock is highly accurate and applicable to the vast majority of tissues in the body, it performs sub-optimally when estimating the age of fibroblasts. In response to this, we recently developed a new epigenetic age estimator, referred to as skin & blood clock that is more accurate in estimating age of different cell types including fibroblasts, keratinocytes, buccal cells, blood cells, saliva and endothelial cells [44]. Studies employing skin & blood clock and the pan-tissue epigenetic age clock revealed a startling consistency of epigenetic age across diverse tissues from the same individual, even though cellular proliferation rates and frequencies of these tissues are not the same [26,44]. This suggests that the ticking of the epigenetic clock is not a reflection of proliferation frequency, which is in stark contrast to telomere length, which enumerates cellular division. It would therefore appear that the process of epigenetic ageing is distinct from that which is driven by telomere-mediated senescence. To understand their relationship or interaction, if one indeed exists, we set out to test the impact of hTERT on epigenetic ageing. To this end we employed wild type hTERT that can prevent telomere attrition and its mutants that cannot [45], with some still able to nevertheless prolong cellular lifespan [46]. Expressing these hTERT constructs in primary cells from numerous donors, ages and cell types, we observe that while hTERT expression can indeed prevent cellular senescence, it does not prevent cells from undergoing epigenetic ageing and that extension of cellular lifespan is sufficient to support continued epigenetic ageing of the cell. These simple observations provide a very important piece to the puzzle of the ageing process because it reveals the distinctiveness of epigenetic ageing from replicative senescence-mediated ageing. They provide further empirical support to the epidemiological observation that hTERT variant that is associated with longer telomeres are also associated with greater epigenetic ageing [47].


Results

To test the effect of hTERT on epigenetic ageing, we first transduced primary neonatal foreskin fibroblasts with hTERT vectors and subjected them and the control isogenic cells, which harbour empty vectors, to continuous culture with passaging. The growth curve in Figure 1A shows that control fibroblasts from neonatal donors A and B (blue and red dots) senesced after about a hundred days in culture and having doubled approximately 50 times (Supplementary Figure 1 and 2A). Unsurprisingly, cells bearing hTERT expression vector bypassed replicative senescence. They proliferated unabated beyond 130 days and 75 cumulative population doubling. The last green and orange dots represent the time-point at which the experiments were terminated, and not the end of cellular viability. These cells have effectively become immortalised. Cellular DNA from a selection of cell passages were subjected to methylation analyses with Illumina EPIC array. The resulting data were processed using the pan-tissue clock and the new skin & blood clock. The results in Figure 1B (for Donor A) and Figure 1C (for Donor B) show control cells to age in culture and this was not perturbed by hTERT expression. Importantly, cells transduced with hTERT not only evaded replicative senescence, their epigenetic ages continued to steadily increase past the point of replicative senescence encountered by their respective isogenic control counterparts (last blue and red dots). While this behaviour is observed with results derived from both epigenetic ageing clocks, the pan-tissue clock clearly displays an off-set from the chronological age of the neonatal cells, which is zero years, as correctly indicated by the skin & blood clock. Incidentally, this systematic offset/error in accurately estimating the epigenetic age of young fibroblasts was one of the reasons for developing the skin & blood clock.




Image

Figure 1. Effects of hTERT on growth and epigenetic ageing of human primary neonatal fibroblasts. (A) Growth dynamics of primary cells from two different donors (A and B) transduced with either empty vector (control) or hTERT expressing vector (hTERT). The ages of a selection of cell passages of donor A (B) and donor B (C) were imputed by the pan-tissue clock (left panel) or the skin & blood clock (right panel). The ages are plotted against cumulative population doubling (CPD) that corresponded to the passage of cells that were analysed.


To ascertain whether the effect of hTERT seen in neonatal foreskin fibroblasts was observable in cells from another tissue and age, we utilised human coronary artery endothelial cells (HCAEC) from adult donor (Donor C; 19 years old). The growth dynamics of these cells as shown in Figure 2A are similar in principle with those of the neonatal fibroblasts, with the difference being the earlier time-point at which the control cells senesce (Supplementary Figure 2B). This is consistent with them being adult cells and as such would have lower replicative potential. As with neonatal fibroblasts, the adult HCAEC expressing hTERT were also immortalised. A startling difference however, is apparent when the ages of these cells were estimated by the two clocks (Figure 2B). While once again the skin & blood clock showed hTERT-expressing cells, which bypassed replicative senescence, to continue ageing steadily, the epigenetic age estimates from the pan tissue clock were much higher and with no significant change in age (Figure 2B). We have observed similar pattern with HCAEC isolated from another donor (26 years old) [44].

Image

Figure 2. Effects of hTERT on growth and epigenetic ageing of adult primary human coronary artery endothelial cells. (A) Growth dynamics of primary cells from one donor (C) transduced with either empty vector (control) or hTERT expression vector (hTERT). (B) The ages of a selection of cell passages of donor C were imputed by the pan-tissue clock (left panel) or the skin & blood clock (right panel). The ages are plotted against cumulative population doubling (CPD) that corresponded to the passage of cells that were analysed.

To further investigate the relationship between hTERT and epigenetic ageing, we employed a previously validated and published panel of hTERT mutants which all possess catalytic activity but are compromised in one or several hTERT properties, namely, extension of replicative lifespan, telomere synthesis or immortalisation (Table 1 and Supplementary Figure 3) [48]. The growth characteristics of the neonatal foreskin fibroblasts transduced with these vectors confirmed that cells expressing wildtype hTERT bypassed replicative senescence (Figure 3) and aged steadily pass the point of replicative senescence encountered by the control cells (Figure 4A). Notably the hTERT IA mutant [46], which can significantly extend replicative lifespan (Figure 3) but can neither replicate telomeres nor immortalise cells, is also able to elicit steady epigenetic ageing pass the point of replicative senescence of the control cells (Figure 4B). This feature is particularly important because it shows that neither telomere synthesis nor immortalisation contribute to the steady rise in epigenetic ageing seen with hTERT-expressing cells. Instead extension of cellular lifespan appears to be the critical property associated with increased epigenetic ageing. Accordingly, the N-DAT116 mutant [46], which was reportedly also able to extend cellular lifespan of human mammary epithelial cells [46,48], but did so only very marginally with neonatal fibroblasts, did not cause a substantial rise in epigenetic ageing (Figure 4C). Likewise the N-DAT92 [46] hTERT mutant that does not increase lifespan also did not increase epigenetic ageing (Figure 4D). The patterns described above largely hold true between the two epigenetic age clocks. It is evident that age scatter plots derived from the pan-tissue clock appear more linear, as is seen in the composite plot in Figure 4E. This is not surprising as the spread of ages estimated by it is much greater than those by the skin & blood clock. Notwithstanding the age off-set that is apparent with the pan-tissue clock, and the greater noise of the skin & blood clock, their results are consistent in showing that while hTERT can prevent replicative senescence, it is ineffective in stopping epigenetic ageing.


We carried out these simple but very long-drawn out experiments to interrogate the connection, if there was one, between replicative senescence (as mediated by telomeres) and epigenetic ageing. In order to interpret these findings correctly, it is necessary to be reminded that epigenetic age, as imputed by the epigenetic clocks is neither a measure of cellular proliferation rate nor a measure of proliferation or passage number. This is evident from the fact that epigenetic age of isogenic tissues (from the same individual) with high and low turn-over rates (blood and heart for example) are similar [26,44]. Epigenetic ageing is also not a measure of senescent cells, as is evident from this study where epigenetic age continues to rise inexorably in hTERT-expressing cells, which do not senesce. These characteristics underline the distinctiveness of epigenetic ageing from replicative senescence-mediated ageing, which supports our previous findings [49] and three genome-wide association studies (GWAS) which did not detect a relationship between telomere length and epigenetic ageing [50–53].

Do these two different ageing processes interact? Since hTERT-expressing cells (subsequently referred to as hTERT cells) exhibit greater age, it would appear that hTERT promotes epigenetic ageing. This however is not the case because hTERT cells do not exhibit higher ages than control cells prior to the point of replicative senescence of the latter. This is evident from the similar gradient of age increase between control and hTERT cells. The acquisition of greater age by hTERT cells after senescence of the control cells is a smooth continuum of the ageing gradient. As such, observations from these experiments do not support the proposition that hTERT stimulates epigenetic ageing. Instead, by causing cells to bypass replicative senescence, hTERT allows the inherent process of epigenetic ageing, which occurs regardless of its presence, to continue. Put simply, while hTERT may appear on the surface, to exacerbate the epigenetic ageing of cells, in truth hTERT, by preventing telomere attrition, prolonged the lifespan of the cells, allowing them growing older (as measured by the epigenetic clocks).

Accordingly, telomere synthesis and immortalisation are not necessary for the acquisition of greater age; a point that is clearly made by hTERT IA mutant, which increased epigenetic age in spite of its inability to maintain telomere length or immortalise cells, but is still able to extend lifespan [46]. It is interesting that although both IA and N-DAT116 mutants are reportedly able to increase life-span of human mammary epithelial cells [46,48], the magnitude of their effect in human neonatal fibroblasts is very different. The hTERT IA mutant, which is far more effective in this regard, is also highly effective in increasing epigenetic age. The hTERT N-DAT116 mutant on the other hand induces only a marginal increase in lifespan and accordingly, no age increase beyond the control cells is evident (measured by the skin and blood clock) and a correspondingly small increase as measured by the pan-tissue clock. These observations are consistent and they point to increased epigenetic ageing in hTERT cells as a result of extension of lifespan.

This conclusion is also consistent with the recently reported genome-wide association study (GWAS) that identified an variant of hTERT that is associated with increased epigenetic ageing [47]. Interestingly, this allele is also associated with longer telomeres. This observation appeared counter-intuitive in the first instance because short telomeres are unequivocally associated with greater age. As such hTERT variants that generate short telomeres would be expected to be associated with increased epigenetic ageing. The apparent paradox disappears when it is realised that while telomere length undoubtedly records the proliferative history of the cell, it also indicates its proliferative or lifespan potential. As such, cells with longer telomeres have longer lifespan, and as empirically demonstrated here, longer lifespan is accompanied by greater epigenetic ageing. In other words, ectopic expression of hTERT (in this study) and expression of a natural hTERT locus variant associated with longer telomeres in vivo (suggested by GWAS) would increase cellular lifespan, with the consequence of greater epigenetic ageing.

The distinctiveness and independence of epigenetic ageing from replicative senescence, exerts a serious impact on ageing intervention strategies. It is likely that re-activation of hTERT expression or elimination of senescent cells will go some way to mitigate the effects of ageing. These measures however, are unlikely to be sufficient to halt ageing altogether since they will not prevent epigenetic ageing. Interventions that prevent or eliminate senescent cells hold great promise for extending human healthspan. Our study suggests that these interventions might not arrest epigenetic aging, which is disconcerting considering the over-whelming evidence that point to the association between accelerated epigenetic ageing and a host of disparate diseases and conditions [17,28–41]. To what extent epigenetic aging of various cells causes the decline in organ function remains an area of active research, but it is arguable that to maximise healthspan there may be a need to develop compounds that target epigenetic ageing as well. In this regard the new skin & blood clock can form the basis of an assay to test for such interventions. This clock out-performs the pan-tissue clock which is already highly accurate for most tissues and cells in the body, but for unknown reasons exhibit a considerable age off-set when used on some cells cultured in vitro. Furthermore, the pan tissue clock also differed substantially from the skin & blood clock when applied to adult human coronary artery cells: unlike the skin & blood clock, it led to a substantial offset and did not reveal the increase of epigenetic age in function of cell growth. We have at present, no explanation for this curious observation. Overall, it appears that the skin & blood clock is more suitable for cultured cells, which is particularly important because the ability to accurately measure cellular age in vitro will allow the yet unknown mechanism of the epigenetic clock to be elucidated more easily. Gratifyingly, the compatibility of the skin & blood clock with cells in vitro does not come with any loss of compatibility with cells in vivo, as was recently described [44].

In summary, these experiments greatly advance our understanding of the connection between epigenetic ageing and senescence-mediated ageing and on this, they have successfully provided empirical evidence that these two mechanisms of ageing are distinct and uncoupled. With the tools that are available (epigenetic clock and primary cells) and the realisation of the difference between these two ageing processes, we are in much improved position to proceed towards understanding the mechanism of epigenetic ageing and its role in human pathology.




https://www.aging-us.com/article/101588/text

Haven't read through completely the whole thing...much more than I posted (see link above) but the gist of it is they don't think immortalizing your bodies cells (i.e. rebuilding your cell's telomeres with telomerase) will make you live longer with one caveat. It would tend to eliminate senescent cells within your body which would likely improve health/longevity; senescent cells for instance not only are non-functional but secret substances that make other cells "sick"; impeding their functionality.

williatw
Posts: 1725
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Sat Oct 20, 2018 1:38 am

Bill Andrews still seems to hold out hope for Telomerase therapy bearing significant fruit:


Bill Andrews speech at RAADfest 2018 (Sept 21, San Diego, CA)

He now seems to be peddling it as an alzheimer treatment, says he has two patients signed to receive treatment sometime this year in December (one of them anyway the other one not until Feb19). Results (optimistically) hoped for by (maybe) February of next year. I would think that given that Brain/CNS cells don't divide much after puberty it would be the least effective against such; to say nothing of the other aspects of alzheimer's like amyloid plaque accumulation.

https://www.youtube.com/watch?v=Mqb1D8Bwkc4

kurt9
Posts: 549
Joined: Mon Oct 15, 2007 4:14 pm
Location: Portland, Oregon, USA

Re: Factor X have we finally found the fountain of Youth?

Postby kurt9 » Sun Oct 21, 2018 2:51 am

My self-experimentation with senolytics commences!

I just took the first batch of Fisetin (700mg) this evening. I will repeat for the next 4 evenings (I'm doing a total of 5 rounds) and see what happens.

I also checked out the LEF website where they talked about a Quercetin/Tocotrienol combination (500mg/125mg daily) for 3 months. I am doing that as well. I will not use the Dasatinib at all as this also attacks functional cells as well and is quite risky. It is also quite expensive. Besides, what I'm reading suggests that Fisetin may actually be BETTER than the D&Q combo. It is certainly much cheaper.

paperburn1
Posts: 2379
Joined: Fri Jun 19, 2009 5:53 am
Location: Third rock from the sun.

Re: Factor X have we finally found the fountain of Youth?

Postby paperburn1 » Sun Oct 21, 2018 6:04 pm

How do you judge effectivity?
I am not a nuclear physicist, but play one on the internet.

Aero
Posts: 1194
Joined: Mon Jun 30, 2008 4:36 am
Location: 92111

Re: Factor X have we finally found the fountain of Youth?

Postby Aero » Sun Oct 21, 2018 8:21 pm

I don't know about telomeres but for health extension, Crispr Pharmaceuticals has something that's pretty sure. It is a targeted and programmable gene editing methodology. It has been approved for human trials. It very specifically targets the programmed gene in the dna strand, snips it out and replaces it, as programmed. The company CEO says that programming the system will be big business for those who can do it. In particular, once a specific gene is programmed, cancer gene, for example, a serum is injected and the system snips out and replaces all of those genes in the body. The cancer is cured because the cells no longer reproduce cancer cells. That part is not a lot different than what has been tried for many years, it is the specificity of gene targeting that is the new breakthrough. Oh, and Crispr Pharmaceuticals is attracting $billions in partnerships and licensing from the major drug companies.

The stock market is still waiting for the cures to be demonstrated and reproduced, it seems.
Aero

williatw
Posts: 1725
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Mon Oct 22, 2018 1:27 am

Aero wrote:I don't know about telomeres but for health extension


Not sure myself although Bill Andrews thinks it does; as I said earlier don't see how it would help much with dementia/Alzheimer's since they are Brain/CNS malfunctions involving cells that don't divide much. Maybe other types of somatic cells; I do agree with Dr Andrews in that this experiment to determine its safety/efficacy (telomerase therapy) in humans is long overdue. As has been said with 150K people dying every day from largely old age we can afford to take some risks. Seems to me that more people are dying as a results of risk avoidance in radical therapies being developed than by rolling the dice and seeing what works.





Aero wrote: Crispr Pharmaceuticals has something that's pretty sure. It is a targeted and programmable gene editing methodology. It has been approved for human trials. It very specifically targets the programmed gene in the dna strand, snips it out and replaces it, as programmed. The company CEO says that programming the system will be big business for those who can do it. In particular, once a specific gene is programmed, cancer gene, for example, a serum is injected and the system snips out and replaces all of those genes in the body. The cancer is cured because the cells no longer reproduce cancer cells. That part is not a lot different than what has been tried for many years, it is the specificity of gene targeting that is the new breakthrough. Oh, and Crispr Pharmaceuticals is attracting $billions in partnerships and licensing from the major drug companies.
The stock market is still waiting for the cures to be demonstrated and reproduced, it seems.


Aubrey de Grey would agree about Crispr. It is closely associated with George Church who I think is as cutting edges as you can get IMHO.


Life Extension & Human Longevity with Dr. Aubrey de Grey on MIND

Published on Oct 11, 2018


Today we explore human longevity and life extension efforts focused on adding healthy years to a person's lifespan, and even reversing the aging process.

My guest is Dr. Aubrey de Grey, a leading voice in the field and the Chief Science Officer of the SENS Research Foundation which is doing pioneering work on significantly extending healthy, active lifespans. Aubrey is a biomedical gerontologist with a degree in Computer Science and a Ph.D. in Biology. He is author of the book "Ending Aging" and Editor-in-Chief of the scientific journal "Rejuvenation Research".

We explore such concepts the "pro aging trance", "longevity escape velocity" and "comprehensive damage repair" that can sustain a human


https://www.youtube.com/watch?v=68XOEAfMj_A&t=6s

williatw
Posts: 1725
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Mon Oct 22, 2018 6:08 am

kurt9 wrote:My self-experimentation with senolytics commences! I just took the first batch of Fisetin (700mg) this evening. I will repeat for the next 4 evenings (I'm doing a total of 5 rounds) and see what happens.


700mg?!...those must be some big azz pills your taking. The only ones I have seen are typically 100mg; though I suppose you could just take seven of those. How did you arrive at the 700mg dosage if you don't mind my asking?

kurt9
Posts: 549
Joined: Mon Oct 15, 2007 4:14 pm
Location: Portland, Oregon, USA

Re: Factor X have we finally found the fountain of Youth?

Postby kurt9 » Mon Oct 22, 2018 3:55 pm

Indeed I take 7 or 8 capsules each day, finishing on Wednesday.

I cam up with the 700mg from a paper that had the factors for converting from animal to human dosages. I tried to attach it to this posting (it won't let me). But you can find it on fightaging.org and do a search for self-experimentation. The article from about a year ago will have a link to the paper with the conversion factors.

paperburn1
Posts: 2379
Joined: Fri Jun 19, 2009 5:53 am
Location: Third rock from the sun.

Re: Factor X have we finally found the fountain of Youth?

Postby paperburn1 » Mon Oct 22, 2018 5:08 pm

so is there a schedule of how often you do this? yearly? quarterly?
I am not a nuclear physicist, but play one on the internet.

kurt9
Posts: 549
Joined: Mon Oct 15, 2007 4:14 pm
Location: Portland, Oregon, USA

Re: Factor X have we finally found the fountain of Youth?

Postby kurt9 » Mon Oct 22, 2018 11:04 pm

paperburn1 wrote:so is there a schedule of how often you do this? yearly? quarterly?


I've not decided yet. I want to see if it works first. If it does, then I'll probably repeat once a year or so. It only cost me $18 for this trial run, which is about as cheap as its going to be for this kind of thing.

I'm also doing the Quercetin/Tocotrienols combo, which is a much slower 3 month trial. I'll know by end of January if this works as well.

Then, its on to Centrophenoxine for Lipofuscin removal, unless I run across a paper between now and next January telling me not to do it.

I expect there will be all kinds of things for me to try over the next 5 years.

I like it, this stuff getting down to the individual vision-quest level. It makes it easier and more enjoyable to ignore all of the mainstream media and internet blather about everything and everyone.

williatw
Posts: 1725
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Wed Oct 24, 2018 11:31 pm

More on Senolytics:

Finally, the drug that keeps you young

Image


Anti-aging pioneer Judith Campisi explains how a recent breakthrough could ward off age-related disease.
by Stephen S. Hall
October 23, 2018


There is a debate about whether there’s a biological limit to the human life span, about 115 years, or whether maximum life span could be extended as long as 130, possibly 150 years. What do you think?

At present, we simply don’t know enough to know whether it will even be possible to extend maximum human life span. Average life span? No problem—it’s already been done. But maximum life span? We just don’t know.


Judith Campisi has been a leading figure in the biology of aging since the early 1990s, when her research on the basic mechanisms of cancer revealed an unexpected finding—that cells enter a phase known as senescence that prevents them from becoming cancerous. More than 25 years later, the insight has led to a new kind of drug that may slow or modestly reverse human aging.

Campisi’s research is on the role of cellular senescence in cancer and other age-related diseases. Senescent cells undergo a transition into a twilight state where they are still active but no longer dividing; research by Campisi and others showed that this was a strategy to derail incipient cancers, which are characterized by runaway cell division and growth. But she and others also discovered that these senescent cells accumulate as we grow older, secreting an array of molecules that promote the tissue degradation associated with aging.



In the past five years, this insight has led to the pursuit of a new class of drugs known as senolytics, which eliminate senescent cells and, in animal experiments, restore more youthful characteristics. Campisi, a professor at the Buck Institute for Research on Aging in Novato, California, cofounded a company called Unity Biotechnology in 2011, which launched a human trial of its first senolytic drug last July.

She recently discussed her work with Stephen S. Hall, a journalist who has been following anti-aging work for more than two decades.

Why should we suddenly get excited about anti-aging drugs again?

There are now tools available to biomedical scientists that simply didn’t exist when I was a graduate student or even a postdoc. So we’re finally able to do experiments that were either considered impossible in some cases or were just dreams 20 or 25 years ago. The other thing that has changed is that the field of senescence—and the recognition that senescent cells can be such drivers of aging—has finally gained acceptance. Whether those drugs will work in people is still an open question. But the first human trials are under way right now.

How specifically does senescence contribute to aging?

The correct way to think about senescence is that it’s an evolutionary balancing act. It was selected for the good purpose of preventing cancer—if [cells] don’t divide, [they] can’t form a tumor. It also optimizes tissue repair. But the downside is if these cells persist, which happens during aging, they can now become deleterious. Evolution doesn’t care what happens to you after you’ve had your babies, so after around age 50, there are no mechanisms that can effectively eliminate these cells in old age. They tend to accumulate. So the idea became popular to think about eliminating them, and seeing if we can restore tissues to a more youthful state.

You’ve suggested that health care could be transformed by senolytic drugs, which eliminate senescent cells. That’s a pretty broad claim.

If we think of aging as a driver for multiple age-related pathologies, the idea would be that a new generation of physicians—we call them geriatricians today—will take a much more holistic approach, and the interventions will also be more holistic. That’s the idea—it would revolutionize the way we’re thinking about medicine nowadays. And just to remind you, 80% of patients in the hospital receiving acute medical attention are over the age of 65. So the idea is that senolytics would be one weapon that geriatricians will have in their arsenal of weapons to treat aging holistically as opposed to one disease at a time.

Image

There is a debate about whether there’s a biological limit to the human life span, about 115 years, or whether maximum life span could be extended as long as 130, possibly 150 years. What do you think?

At present, we simply don’t know enough to know whether it will even be possible to extend maximum human life span. Average life span? No problem—it’s already been done. But maximum life span? We just don’t know.


If you look at C. elegans, a little worm, the world record for extending the life span of that animal is 10-fold. For humans that would be unbelievable, right? A thousand years. But if you go up the evolutionary scale just a little bit, to the fruit fly Drosophila, it’s maybe twofold. And then if you go to a mouse, most of the really high-profile papers extend its life span maybe 20%, sometimes 30%. So think about the difference between a mouse and a human. We’re something like 97% genetically identical, meaning we have the same genes. And yet there’s a 30-fold difference in our life span.

So it seems to me that in order for evolution to evolve a 30-fold difference in life span with so few really clear genetic differences, evolution maybe had to tweak hundreds, if not thousands, of genes. It’s unlikely at the present time that we will find a single drug that’s going to be able to do what ­evolution did.

Some Silicon Valley enthusiasts have been saying that life-span extension up to 500 or 1,000 years is feasible.

Well, it’s religion. It’s not science. I mean, that’s all I can say. It’s based on belief, not based on any data. People are certainly welcome to believe whatever they want to believe. But it doesn’t make it true!

You’ve frequently emphasized that aging is a complex process, and that modifying it is not going to be quick or easy. Yet we all yearn for a solution.

Again, don’t confuse aging and death. I am optimistic that we will experience medical interventions that will extend—the buzzword now is “health span.” I think what terrifies people—certainly what terrifies me—is watching, for example, my mom, who is well into her 90s. She’s losing cognitive function, she doesn’t walk as well—and she’s in pretty good shape! There are lots of people at her age who are confined to wheelchairs. That’s aging, and that’s terrifying. I am optimistic that we’re on the cusp of understanding enough about that process to be able to intervene. And that people like us, who are not at that point, will benefit.

But we’re still going to die. I’ll remind you of the mouse models, where we eliminate senescent cells. There’s a significant increase in median life span, but there’s no increase in maximum life span. In a way, the mice died healthier. I think that’s the goal, and I think that that’s what the venture capitalists are hoping for, because that will be the kind of intervention that will be broadly applicable and will be very desirable. The conflict is with those who think that we’re going to live to be 200 or 300 or more years old. That’s not realistic at this point.

Let’s say we are successful at slowing down or reversing aging, or extending health span. Are there any social or cultural impacts that you have concerns about?

No. In my lifetime, the population of the earth has not quite doubled, but it’s getting there. That’s unsustainable. The truth of the matter is, not having people die is not going to add much to the population of the earth the way the current rate at which we’re producing new people is ruining the earth. So I think that this is ridiculous.

So I really don’t see a downside to this. There are problems, but I don’t think extending health span is going to exacerbate those problems.





https://www.technologyreview.com/s/6122 ... you-young/

williatw
Posts: 1725
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Thu Oct 25, 2018 12:18 am

kurt9 wrote:Indeed I take 7 or 8 capsules each day, finishing on Wednesday.

I cam up with the 700mg from a paper that had the factors for converting from animal to human dosages. I tried to attach it to this posting (it won't let me). But you can find it on fightaging.org and do a search for self-experimentation. The article from about a year ago will have a link to the paper with the conversion factors.


I am starting with the Fisetin as well starting today. Not as brave as you will try 200mg a day (one 100mg capsule in the morning one in the evening) will see how that work out.


Return to “General”

Who is online

Users browsing this forum: No registered users and 11 guests