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New Rapamycin Study- up to 60% increase in mouse lifespan- Anyone Experimenting With This?

rapamycin

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#301 VP.

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Posted 03 April 2017 - 07:08 PM

Dog study results are now published. https://link.springe...1357-017-9972-z

To summarize, this initial study of rapamycin in healthy, middle-aged dogs showed that low-dose rapamycin treatment is safe over a period of 10 weeks and appears to recapitulate some of the same beneficial effects that have been described for mTOR inhibition in mice. The low number of dogs and multiple comparisons performed limit our statistical power, and the relatively short duration did not allow us to determine whether the rapamycin-treated dogs had increased lifespan and healthspan compared to placebo. The absence of significant side effects here is consistent with findings from studies on marmosets in captivity (Ross et al. 2015) as well as prior studies of rapamycin in laboratory dogs (Yi et al. 2014). Unlike these prior studies, however, the dogs in this study were living in their normal home environment, providing an important demonstration that rapamycin can be safely administered to companion dogs with the potential for significant health benefits. Based on these findings, we are planning additional randomized clinical trials involving larger cohorts of middle-aged dogs that will be studied over a longer period of time. This will allow us to perform more powerful analyses of rapamycin’s effects on heart function and behavior and help us determine whether there are differences in mortality, as well as the onset and prevalence of the various diseases that share aging as their common risk factor.

The relatively small number of dogs studied here prohibits us from reaching a definite conclusion regarding any behavioral effects of rapamycin. However, it is interesting to note that some changes in behavior that were considered to be positive by owners appeared to occur with greater frequency in the rapamycin-treated dogs. Seventy percent (7/10) of the owners whose dogs received the higher rapamycin dose reported that their dog displayed increased activity and energy, as did 40% (2/5) of those whose dogs received the lower dose, compared to 25% (2/8) of owners whose dogs received the placebo. While we make no claims as to whether this represents a real effect of rapamycin in these dogs, such an effect would reflect previous reports of increased activity in rapamycin-treated mice (Flynn et al. 2013; Miller et al. 2011) and would be consistent with anecdotal reports from owners who have independently begun treating their dogs with rapamycin (Cohen 2016).

 

It is interesting to note that the mean corpuscular volume was significantly diminished in rapamycin-treated dogs after 10 weeks when compared to that of placebo. Hematocrit did not change significantly between treatment and placebo (P = 0.803), which in combination with the observed decrease in the MCV may indicate longer red blood cell survival, as the MCV tends to decrease as the red blood cells age. A decrease in red blood cell size in response to treatment with rapamycin has previously been described in vitro (Edinger et al. 2003). It is also interesting to note that older humans have lowered red blood cell survival times, which are reflected in an MCV increase with age, and increased MCV has also been linked to decreased cognitive performance in older humans (Gamaldo et al. 2013). This may indicate an attenuation by rapamycin of an age-related change in red blood cell volume that is known to predict adverse outcomes in humans, and it provides additional justification for studying cognitive function in future studies of rapamycin in aging dogs.


Edited by VP., 03 April 2017 - 07:13 PM.

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#302 VP.

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Posted 05 April 2017 - 05:54 PM

New Function Discovered For Compound That May Help Slow Aging (Rapamycin)

A study just published in Aging Cell outlines a new understanding of how this compound works.

“It’s possible this could provide a new therapeutic approach to neurologic disease,” said Viviana Perez, an assistant professor in the Department of Biochemistry and Biophysics in OSU’s College of Science, expert on the biological processes of aging and principal investigator in the Linus Pauling Institute.

Scientists have now identified two mechanisms of action of rapamycin. One was already known. The newly-discovered mechanism is what researchers say might help prevent neurologic damage and some related diseases.

“The value of rapamycin is clearly linked to the issue of cellular senescence, a stage cells reach where they get old, stop proliferating and begin to secrete damaging substances that lead to inflammation,” Perez said. “Rapamycin appears to help stop that process.”

Prior to this research, it had only been observed that there was one mechanism of action for rapamycin in this process. Scientists believed it helped to increase the action of Nrf2, a master regulator that can “turn on” up to 200 genes responsible for cell repair, detoxification of carcinogens, protein and lipid metabolism, antioxidant protection and other factors. In the process, it helped reduce levels of SASP.

The new study concluded that rapamycin could also affect levels of SASP directly, separately from the Nrf2 pathway and in a way that would have impacts on neurons as well as other types of cells.

“Any new approach to help protect neurons from damage could be valuable,” Perez said. “Other studies, for instance, have shown that astrocyte cells that help protect neuron function and health can be damaged by SASP. This may be one of the causes of some neurologic diseases, including Alzheimer’s disease.”

http://neurosciencen...-function-6344/

http://onlinelibrary...acel.12587/full

 


Edited by VP., 05 April 2017 - 05:56 PM.

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#303 Jaris

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Posted 05 April 2017 - 06:53 PM

New Function Discovered For Compound That May Help Slow Aging (Rapamycin)

A study just published in Aging Cell outlines a new understanding of how this compound works.

“It’s possible this could provide a new therapeutic approach to neurologic disease,” said Viviana Perez, an assistant professor in the Department of Biochemistry and Biophysics in OSU’s College of Science, expert on the biological processes of aging and principal investigator in the Linus Pauling Institute.

Scientists have now identified two mechanisms of action of rapamycin. One was already known. The newly-discovered mechanism is what researchers say might help prevent neurologic damage and some related diseases.

“The value of rapamycin is clearly linked to the issue of cellular senescence, a stage cells reach where they get old, stop proliferating and begin to secrete damaging substances that lead to inflammation,” Perez said. “Rapamycin appears to help stop that process.”

Prior to this research, it had only been observed that there was one mechanism of action for rapamycin in this process. Scientists believed it helped to increase the action of Nrf2, a master regulator that can “turn on” up to 200 genes responsible for cell repair, detoxification of carcinogens, protein and lipid metabolism, antioxidant protection and other factors. In the process, it helped reduce levels of SASP.

The new study concluded that rapamycin could also affect levels of SASP directly, separately from the Nrf2 pathway and in a way that would have impacts on neurons as well as other types of cells.

“Any new approach to help protect neurons from damage could be valuable,” Perez said. “Other studies, for instance, have shown that astrocyte cells that help protect neuron function and health can be damaged by SASP. This may be one of the causes of some neurologic diseases, including Alzheimer’s disease.”

http://neurosciencen...-function-6344/

http://onlinelibrary...acel.12587/full

 

This is really exciting. There have already been several studies - up to and including mice - that showed it helps greatly with Parkinson's. Thanks for the update, VP. Keep them coming!

 

Also, Dr Alan Green has just finished his web site here: https://rapamycintherapy.com/


Edited by Jaris, 05 April 2017 - 07:27 PM.

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#304 APBT

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Posted 06 April 2017 - 12:53 AM

Koschei the immortal and anti-aging drugs

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#305 VP.

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Posted 17 April 2017 - 07:43 PM

Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment

We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1df/dfdwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls.

https://genomebiolog...3059-017-1186-2

 

Tick tock, stay ahead of the aging clock

Aging in humans (and animals) can be seen as either an inevitable process of wear and tear or as an inherent biological program by which the lifespan of each species is more or less predetermined. Recent research has shown that DNA methylation, an epigenetic modification which alters how DNA is read and expressed without altering the underlying sequence, can show age-related changes.  A sub-set of these modifications are so accurate that chronological age in humans can be predicted +/- 3.6 years from any tissue or fluid in the body. This is by far the best biomarker of age available and is referred to as the epigenetic clock.   Interestingly, analysis of DNA methylation can also provide information on biological age, which is a measure of how well your body functions compared to your chronological age. For instance, people suffering from fatty liver disease have a faster ticking clock, while centenarians have a slower clock.

https://www.scienced...70412124358.htm

 

Is there anyway to test your own genes using 82 Illumina DNA methylation array?  Would be nice to see if Rapamycin and other interventions are working.

https://labs.genetic...orvath/dnamage/

 

 


Edited by VP., 17 April 2017 - 08:12 PM.

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#306 Jaris

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Posted 19 April 2017 - 07:07 AM

Here's a video about how too much mTOR activity can lead to cancer and how CR or Rapamycin may block it. Also, don't drink milk!

 


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#307 Captain Obvious

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Posted 19 April 2017 - 07:33 AM

Here's a video about how too much mTOR activity can lead to cancer and how CR or Rapamycin may block it. Also, don't drink milk!

 

 

Why shouldn't you drink milk?



#308 aribadabar

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Posted 19 April 2017 - 06:06 PM

 

Here's a video about how too much mTOR activity can lead to cancer and how CR or Rapamycin may block it. Also, don't drink milk!

 

 

Why shouldn't you drink milk?

 

 

You are true to your name  :)

It is obvious : dairy/milk proteins contain growth factors which induce elevated mTOR signaling which is pro-inflammatory and inflammation is a major component of cancer etiology.



#309 Captain Obvious

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Posted 19 April 2017 - 06:18 PM

 

 

 

 

You are true to your name   :)

It is obvious : dairy/milk proteins contain growth factors which induce elevated mTOR signaling which is pro-inflammatory and inflammation is a major component of cancer etiology.

 

 

Well someone has to ask the obvious stuff. :)

What research evidence is there that milk proteins are absorbed intact and have measurable biological effects in humans in amounts found in regular milk consumption?

AFAIK most proteins are denaturated by the digestive tract. It's one of the reasons HGH needs to be injected.


Edited by Captain Obvious, 19 April 2017 - 06:20 PM.


#310 PAMPAGUY

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Posted 19 April 2017 - 07:31 PM

Would highly recommend reading Dr. Alan Green's (semi-retired pathologist) website dealing with the anti aging formula of   Mikhail Blagosklonny , Phd., the foremost authority on rapamycin treatment for old age.   I have an appointment for May 11th.  Will report back then.  Dr. Green is the only person, I know of who has documented his long term (14 months) experimentation of taking the rapa formula. (rapa+metformin+aspirin+Angiotensin II inhibitors)  and posting his lab work.

 

https://rapamycintherapy.com/


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#311 maxwatt

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Posted 19 April 2017 - 10:12 PM

....

 

Is there anyway to test your own genes using 82 Illumina DNA methylation array?  Would be nice to see if Rapamycin and other interventions are working.

https://labs.genetic...orvath/dnamage/

 

There is a way to test.  Mind posted a link to a lab that will perform DNA methylation analysis:  Osiris Green

For $65, not too expensive.  It would behoove us to get before and after measurements.  For those who've jumped the gun, I expect there would be continued improvement with ongoing use, as no one has been using Rapamycin all that long.

 

PS there is a 20 dollar discount if you enter the code "longecity" at checkout


Edited by maxwatt, 19 April 2017 - 10:37 PM.

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#312 tintinet

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Posted 19 April 2017 - 10:16 PM





You are true to your name :)
It is obvious : dairy/milk proteins contain growth factors which induce elevated mTOR signaling which is pro-inflammatory and inflammation is a major component of cancer etiology.


Well someone has to ask the obvious stuff. :)

What research evidence is there that milk proteins are absorbed intact and have measurable biological effects in humans in amounts found in regular milk consumption?

AFAIK most proteins are denaturated by the digestive tract. It's one of the reasons HGH needs to be injected.

http://www.medscape....warticle/777311

#313 maxwatt

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Posted 20 April 2017 - 04:17 AM

No more cheese :(



#314 Razor444

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Posted 21 April 2017 - 05:01 PM

Rapa is metabolised by CYP 3A4.

 

 

Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies

Curcumin, a specific secondary metabolite of Curcuma species, has potentials for a variety of beneficial health effects. It is nowadays used as a dietary supplement. Everolimus (EVL) is an immunosuppressant indicated for allograft rejection and cancer therapy, but with narrow therapeutic window. EVL is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). This study investigated the effect of coadministration of curcumin on the pharmacokinetics of EVL in rats and the underlying mechanisms. EVL (0.5 mg/kg) was orally administered without and with 50 and 100 mg/kg of curcumin, respectively, in rats. Blood samples were collected at specific time points and EVL concentrations in blood were determined by QMS® immunoassay. The underlying mechanisms were evaluated using cell model and recombinant CYP 3A4 isozyme. The results indicated that 50 and 100 mg/kg of curcumin significantly decreased the AUC0-540 of EVL by 70.6% and 71.5%, respectively, and both dosages reduced the Cmax of EVL by 76.7%. Mechanism studies revealed that CYP3A4 was markedly activated by curcumin metabolites, which apparently overrode the inhibition effects of curcumin on P-gp. In conclusion, oral intake of curcumin significantly decreased the bioavailability of EVL, a probe substrate of P-gp/CYP 3A4, mainly through marked activation on CYP 3A4.

 

 


Edited by Razor444, 21 April 2017 - 05:02 PM.

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#315 Jaris

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Posted 21 April 2017 - 06:47 PM

 

Rapa is metabolised by CYP 3A4.

 

 

Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies

Curcumin, a specific secondary metabolite of Curcuma species, has potentials for a variety of beneficial health effects. It is nowadays used as a dietary supplement. Everolimus (EVL) is an immunosuppressant indicated for allograft rejection and cancer therapy, but with narrow therapeutic window. EVL is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). This study investigated the effect of coadministration of curcumin on the pharmacokinetics of EVL in rats and the underlying mechanisms. EVL (0.5 mg/kg) was orally administered without and with 50 and 100 mg/kg of curcumin, respectively, in rats. Blood samples were collected at specific time points and EVL concentrations in blood were determined by QMS® immunoassay. The underlying mechanisms were evaluated using cell model and recombinant CYP 3A4 isozyme. The results indicated that 50 and 100 mg/kg of curcumin significantly decreased the AUC0-540 of EVL by 70.6% and 71.5%, respectively, and both dosages reduced the Cmax of EVL by 76.7%. Mechanism studies revealed that CYP3A4 was markedly activated by curcumin metabolites, which apparently overrode the inhibition effects of curcumin on P-gp. In conclusion, oral intake of curcumin significantly decreased the bioavailability of EVL, a probe substrate of P-gp/CYP 3A4, mainly through marked activation on CYP 3A4.

 

 

 

Maybe everyone already knows this, but curcumin and cumin are totally different. Curcumin is a component of turmeric, and cumin comes from a seed of a different plant. They are both great antioxidants, etc but they have completely different chemical components. So, if you're like me and love cumin, don't freak. But if you are into turmeric or curcumin suppliments, this news might bum you out. To save you time looking for yourself:

http://www.differenc...in-and-cumin-2/



#316 Jaris

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Posted 24 April 2017 - 02:19 AM

I just stumbled across this year-old study on the safety of rapamycin in marmosets. It's new to me, but they've evidently been working on a follow-on study for about a year. To sum it up:
 

... first to examine the metabolic consequences of rapamycin dosing in healthy, non-human primates. In addition to metabolic function, the researchers found that the encapsulated rapamycin was well tolerated by the marmosets.

"This initial study with marmosets as a model for human aging has allowed us to evaluate the efficacy of a new intervention treatment that looked promising in other animal model species for both healthspan and lifespan extension," said Dr. Corinna Ross, lead author of the study and Assistant Professor Biology, Texas A&M University San Antonio.

"The results are encouraging," said Dr. Suzette Tardif, Associate Director of SNPRC and co-investigator on the study. "Marmosets also offer a unique non-human primate model that will allow us to further evaluate not just the safety but the effectiveness of treatment with rapamycin."

Due to results from this study, a grant for $2.7 million was awarded to the Barshop Institute and SNPRC by the National Institute on Aging to fund a new study to determine the effects of rapamycin lifespan and markers of healthy aging for a cohort of marmosets that have already reached middle age.

 

https://www.scienced...60209105352.htm

 
I'll post more after I've looked into it. Does anyone have any info on the follow-on study? Marmosets have a typical lifespan of 12 years, so since they started with a "middle aged" cohort, we might still have another 4-5 years to wait. Unless, of course, R works really well!  :-D

Edited by Jaris, 24 April 2017 - 02:57 AM.

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#317 PAMPAGUY

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Posted Today, 01:11 AM

Parkinsons symptoms reversed Jaris.

 

 

https://www.fightagi...-a-mouse-model/

 

 







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