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Rapamycin

Where to purchase:

• Siromus at ReliableRXPharmacy

Sirolimus - Wikipedia - "Sirolimus (INN/USAN), also known as rapamycin, is a macrolide produced by the bacteria Streptomyces hygroscopicus. It has immunosuppressant functions in humans and is used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. It prevents activation of T cells and B cells by inhibiting their response to interleukin-2 (IL-2)"

News & Research:

• Rapamycin increases Alzheimer's-associated plaques in mice, study finds - Science Daily, 6/7/22 - "The study is relevant to β-amyloid-associated Alzheimer's and is not generalizable to other Alzheimer's pathologies ... Findings from this study may give the medical world a reason to pause testing rapamycin on anyone at risk of Alzheimer's disease. "Rapamycin may have benefits in terms of suppressing the immune system and as a tumor suppressor," Dr. Bhat said. "But in a situation where it negatively impacts the expression of Trem2 or other critical proteins, it may have a detrimental effect. We caution that rapamycin's benefits in β-amyloid-associated Alzheimer's must be studied more carefully.""
• Multiple treatments to slow age-related muscle wasting - Science Daily, 4/20/22 - "Researchers led by Professor Markus Rüegg at the Biozentrum of the University of Basel have demonstrated in mice that both calorie restriction and the drug rapamycin have a positive effect on aging skeletal muscle" - See siromus at ReliableRXPharmacy and inhousepharmacy.vu.
• Rapamycin changes the way our DNA is stored - Science Daily, 6/9/21 - "the increased levels of certain histone proteins in a specific gut cell type called enterocytes reduced tumour growth, improved gut health and extended lifespan of the animals ... Given the central role of histones on DNA storage in the cell, this finding not only broadens our knowledge on the ageing process, but also provides new possibilities for targeted therapeutic interventions against ageing" - See Siromus at ReliableRXPharmacy.
• Muscle aging: Stronger for longer - Science Daily, 9/9/20 - "Contrary to our expectations, the long-term mTORC1 suppression with rapamycin is overwhelmingly beneficial for skeletal muscle aging in mice, preserving muscle size and strength ... There is currently no effective pharmacological therapy to treat sarcopenia. This study provides hope that it may be possible to slow down age-related muscle wasting with treatments that suppress mTORC1 and thereby extend the autonomy and life quality of elderly people"
• Immune-regulating drug improves gum disease in mice - Science Daily, 4/28/20 - "Rapamycin is an immune-suppressing drug currently used to prevent organ rejection in transplant recipients. Previous studies in mice have also suggested that it may have life-extending effects, which has led to interest in studying the drug's effects in many age-related diseases ... added the drug to the food of middle-aged mice for eight weeks and compared their oral health with untreated mice of the same age ... the treated mice had more bone than the untreated mice, and had actually grown new bone during the period they were receiving rapamycin ... The work also showed that rapamycin-treated mice had less gum inflammation. Genetic sequencing of the bacteria in their mouths also revealed that the animals had fewer bacteria associated with gum disease and a mix of oral bacteria more similar to that found in healthy young mice ... By targeting this aging process through rapamycin treatment, our work suggests that we can delay the progress of gum disease and actually reverse its clinical features ... while rapamycin is already used to treat certain conditions, it can make people more susceptible to infections and may increase their risk of developing diabetes, at least at the higher chronic doses typically taken by organ transplant patients"
  • Sirolimus - wiki - "Sirolimus, also known as rapamycin, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection and treat a rare lung disease called lymphangioleiomyomatosis.[4][5][6] It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants"
• Rapamycin may slow skin aging - Science Daily, 11/25/19 - "In the current Drexel-led study, 13 participants over age 40 applied rapamycin cream every 1-2 days to one hand and a placebo to the other hand for eight months. The researchers checked on subjects after two, four, six and eight months, including conducting a blood test and a biopsy at the six- or eight-month mark ... After eight months, the majority of the rapamycin hands showed increases in collagen protein, and statistically significant lower levels of p16 protein, a key marker of skin cell aging. Skin that has lower levels of p16 has fewer senescent cells, which are associated with skin wrinkles. Beyond cosmetic effects, higher levels of p16 can lead to dermal atrophy, a common condition in seniors, which is associated with fragile skin that tears easily, slow healing after cuts and increased risk of infection or complications after an injury"
• Rapamycin prevents age-related brain vascular deterioration in rats - Science Daily, 11/6/19 - "In the study, published Nov. 6 in the journal Aging Cell, researchers began rats on a diet including low-dose rapamycin at 19 months old (past middle age in rat years). Rapamycin treatment in daily food continued until the mice were of advanced age -- 34 months old -- almost double the age they were when they started treatment. "Essentially this is as old as these rats can get. These animals were very old but still, blood circulation in the brain was exactly the same as when they started treatment," said study senior author Veronica Galvan, Ph.D., professor of cellular and integrative physiology at UT Health San Antonio" - But it's expensive.  Here's one site I've found.
• Fruit flies live longer with combination drug treatment - Science Daily, 9/30/19 - "lithium as a mood stabiliser, trametinib as a cancer treatment and rapamycin as an immune system regulator ... The three drugs in question act on different proteins of this network to slow the ageing process and delay the onset of age-related death ... Each drug individually extended lifespan by an average of 11%, while pairing two drugs extended lifespan by roughly 30%. When the three drugs were combined, the fruit flies lived 48% longer than flies in a control group that were not given the treatment ... Previous studies in fruit flies have achieved lifespan extensions of about 5-20%, so we found it was quite remarkable that this drug combination enabled them to live 48% longer ... Rapamycin has undesirable effects on fat metabolism, which can be similar to insulin resistance in people, but lithium appeared to cancel out this effect when the two drugs were given together" - See lithium supplements at Amazon.com.
• This pill could make your dog (and maybe you) live longer - CNN, 10/6/16 - "We knew we could go to Mexico and get rapamycin or order it online, but we wanted to be guided by a veterinarian, by a professional ... a month after his stroke, Sherman was so weak, he had to be fed by hand and carried everywhere ... rapamycin changed all that ... The third day after taking rapamycin, he could eat on his own. By the seventh day, he was walking on his own ... Sixteen months later, the dog who had been given two months to live is still alive, and while clearly old, he's still active and able to run around the yard ... The list of things that can go wrong is long and horrifying: cancer, diabetes, infections and more ... Of the 53 patients on the lowest dose of rapamycin, 22 suffered some side effect, most commonly mouth sores ... he prefers to think in terms of treatments that will delay the onset of diseases of aging, such as dementia or heart disease. In mice, rapamycin has been shown to slow these two types of declines, as well as several others"
• Research explains action of drug that may slow aging, related disease - Science Daily, 5/20/14 - "Rapamycin, an antibiotic and immunosuppressant approved for use about 15 years ago, has drawn extensive interest for its apparent ability -- at least in laboratory animal tests -- to emulate the ability of dietary restriction in helping animals to live both longer and healthier ... this medication has some drawbacks, including an increase in insulin resistance that could set the stage for diabetes ... a combination of rapamycin and another drug to offset that increase in insulin resistance might provide the benefits of this medication without the unwanted side effect ... Laboratory mice that have received rapamycin have reduced the age-dependent decline in spontaneous activity, demonstrated more fitness, improved cognition and cardiovascular health, had less cancer and lived substantially longer than mice fed a normal diet ... the drug metformin can address that concern"

Abstracts:

• Towards natural mimetics of metformin and rapamycin - Aging (Albany NY). 2017 Nov 15 - "The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferin A (both)" - [Nutra USA] - See ginseng at Amazon.com and ashwagandha at Amazon.com.  See metformin at ReliableRX.
  • Withaferin A - wikipedia.org - "Withaferin A is a steroidal lactone, derived from Acnistus arborescens,[1] Withania somnifera[2] (Indian Winter cherry or Ashwagandha in Sanskrit) and other members of Solanaceae family"
• Rapamycin for longevity: opinion article - Aging (Albany NY). 2019 Oct 15 - "From the dawn of civilization, humanity has dreamed of immortality. So why didn’t the discovery of the anti-aging properties of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as anti-aging drugs today. Furthermore, the alternative to the reversible (and avoidable) side effects of rapamycin/everolimus are the irreversible (and inevitable) effects of aging: cancer, stroke, infarction, blindness and premature death. I will also discuss why it is more dangerous not to use anti-aging drugs than to use them and how rapamycin-based drug combinations have already been implemented for potential life extension in humans. If you read this article from the very beginning to its end, you may realize that the time is now ... Twenty years ago, it was thought that rapamycin might increase the risk of cancer (see a forthcoming review “Understanding the side effects of rapamycin”). Despite that concern, it was revealed that rapamycin actually prevents lymphoma and some types of cancer in transplant patients [20–27]. Currently, in fact, rapamycin analogs, everolimus and temsirolimus, are widely used in cancer therapy. Furthermore, rapamycin is the most effective known cancer-preventive agent in mice [25,28–32] extending the lifespan of cancer-prone mice [33–36]. It has even been suggested that rapamycin extends lifespan by preventing cancer"
• Stimulation of Hair Growth by Small Molecules that Activate Autophagy - Cell Rep 2019 Jun 18 - "We report that quiescent (telogen) hair follicles can be stimulated to initiate anagen and hair growth by small molecules that activate autophagy, including the metabolites α-ketoglutarate (α-KG) and α-ketobutyrate (α-KB), and the prescription drugs rapamycin and metformin, which impinge on mTOR and AMPK signaling. Stimulation of hair growth by these agents is blocked by specific autophagy inhibitors, suggesting a mechanistic link between autophagy and hair regeneration"
• I Goolged rapamycin and heart failure. There were a lot of studies. Here's some that were near the top of the search:
  • Rapamycin regulates the balance between cardiomyocyte apoptosis and autophagy in chronic heart failure by inhibiting mTOR signaling - Int J Mol Med. 2020 Jan - "Rapamycin treatment for 4 weeks inhibited the mTOR and ER stress pathways. Furthermore, rapamycin prevented angiotensin II-induced H9c2 cell apoptosis and promoted autophagy by inhibiting the mTORC1 and ER stress pathways. These results demonstrated that rapamycin reduced cardiomyocyte apoptosis and promoted cardiomyocyte autophagy, by regulating the crosstalk between the mTOR and ER stress pathways in chronic HF" -
  • Anti-Remodeling Effects of Rapamycin in Experimental Heart Failure: Dose Response and Interaction with Angiotensin Receptor Blockade - PLoS One 2013 Dec 3 - "Rapamycin treatment decreased mTOR mediated regulators of protein synthesis and increased mTOR mediated regulators of autophagy. Losartan monotherapy did not attenuate remodeling, whereas Losartan added to rapamycin provided no incremental benefit over rapamycin alone. These data lend support to investigation of low dose rapamycin as a novel therapy in human HF"
• T cells: a ‘hidden corner’ to be explored for treating heart failure - European Heart Journal, ehac241 , 13 May 22 - Interesting article. I think it's saying that t-cells inhibit the repair of the heart. I've been taking rapamycin for anti-aging but I was worried because it inhibits t-cells but ever since I've been taking it, I've felt on top of the world. Maybe the t-cell inhibition and the subsequent heart repair is the reason.
  • Adult T-cells impair neonatal cardiac regeneration - European Heart Journal, ehac188 13 Apr 22 - "Patients who survive a myocardial infarction (MI) often develop chronic heart failure due to the heart’s poor regeneration capacity. We hypothesized that the cardiac ‘regenerative-to-scarring’ transition might be driven by the perinatal shifts observed in the circulating T-cell compartment ... The perinatal loss of myocardial regenerative capacity was paralleled by a baseline increase in αβ-T cell (CD4+ and CD8+) numbers ... The perinatal loss of myocardial regenerative capacity was paralleled by a baseline increase in αβ-T cell (CD4+ and CD8+) numbers. Strikingly, P1-infarcted mice reconstituted with adult T-cells shifted to an adult-like healing phenotype, marked by irreversible cardiac functional impairment and increased fibrosis. Infarcted neonatal mice harbouring adult T-cells also had more monocyte-derived macrophage recruitment, as typically seen in adults. At the transcriptome level, infarcted P1 hearts that received isolated adult T-cells showed enriched gene sets linked to fibrosis, inflammation, and interferon-gamma (IFN-γ) signalling ... Physiological T-cell development or adoptive transfer of adult IFN-γ-producing T-cells into neonates contributed to impaired cardiac regeneration and promoted irreversible structural and functional cardiac damage. These findings reveal a trade-off between myocardial regenerative potential and the development of T-cell competence"