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Anti-aging Research > Rapamycin
Rapamycin
Where to purchase:
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:
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Study of Sirolimus in
Patients With Advanced Pancreatic Cancer - clinicaltrials.gov, 9/7/18 -
"In preclinical studies, investigators found that
rapamycin can effectively inhibit the angiogenesis of liver Cancer led by
tumor-associated macrophages (TAM), thereby inhibiting the progression of liver
Cancer.In vitro experiments on pancreatic cancer showed that rapamycin can
directly inhibit the proliferation of pancreatic cancer cells.After the
treatment with rapamycin in the homologous xenograft tumor model of mice, it was
found that the tumor growth of mice was significantly inhibited. Further
analysis suggested that rapamycin not only directly inhibits tumor
proliferation, but also reverses the immune suppressive microenvironment of
pancreatic cancer and promotes the T-cell-mediated anti-tumor immune
response.Preclinical findings suggest that rapamycin may benefit survival in
pancreatic cancer patients, which makes us very interested in the efficacy of
rapamycin in patients with advanced pancreatic cancer" - See
Siromus (rapamycin) at ReliableRXPharmacy.
-
Rapamycin improves the
quality and developmental competence of in vitro matured oocytes in aged mice
and humans - Aging (Albany NY) 2022 Nov 26 - "Women
over age 35 suffer from the inadequate number and poor quality of oocytes during
assisted reproductive treatment, and making full use of the oocytes by in vitro
maturation (IVM) is crucial. Rapamycin could improve the developmental
competences of the post-maturation oocytes during in vitro aging, yet its
effects on the IVM process of oocytes from an aged population were not clear ...
Overall, rapamycin improved IVM outcomes of oocytes from aged mice and older
women. The specific mechanism of the positive effects of rapamycin on IVM
outcomes might be reducing ROS levels, mitigating DNA damage, and promoting
developmental potential"
-
Early or late-life treatment
with acarbose or rapamycin improves physical performance and affects cardiac
structure in aging mice -
J Gerontol A Biol Sci Med Sci 2022 Nov 7 -
"Pharmacological treatments can extend lifespan in mice. For optimal translation
in humans, treatments should improve health during aging, and demonstrate
efficacy when started later in life. Acarbose (ACA) and Rapamycin (RAP) extend
lifespan in mice when treatment is started early or later in life. Both drugs
can also improve some indices of healthy aging, although there has been little
systematic study of whether health benefits accrue differently depending on the
age at which treatment is started. Here we compare the effects of early (4
month) versus late (16 month) onset ACA or RAP treatment on physical function
and cardiac structure in genetically heterogeneous aged mice. ACA or RAP
treatment improve rotarod acceleration and endurance capacity compared to
controls, with effects that are largely similar in mice starting treatment from
early or late in life. Compared to controls, cardiac hypertrophy is reduced by
ACA or RAP in both sexes regardless of age treatment onset. ACA has a greater
effect on the cardiac lipidome than RAP, and effects of early life treatment are
recapitulated by late life treatment. These results indicate that late life
treatment with these drugs provide at least some of the benefits of life long
treatment, although some of the benefits occur only in males, which could lead
to sex differences in health outcomes later in life"
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Rapamycin treatment early in life reprograms aging:
hyperfunction theory and clinical practice - Aging
(Albany NY) 2022 Oct 24 - "Making
provocative headlines, three outstanding publications
demonstrated that early-life treatment with rapamycin,
including treatments during developmental growth, extends
lifespan in animals, confirming predictions of hyperfunction
theory, which views aging as a quasi-program (an unintended
continuation of developmental growth) driven in part by mTOR.
Despite their high theoretical importance, clinical
applications of two of these studies in mice, Drosophila and
Daphnia cannot be implemented in humans because that would
require growth retardation started at birth. A third study
demonstrated that a transient (around 20% of total lifespan
in Drosophila) treatment with rapamycin early in Drosophila
adult life is as effective as lifelong treatment, whereas a
late-life treatment is not effective. However, previous
studies in mice demonstrated that a transient late-life
treatment is highly effective. Based on hyperfunction
theory, this article attempts to reconcile conflicting
results and suggests the optimal treatment strategy to
extend human lifespan"
-
Rapamycin/metformin co-treatment normalizes insulin
sensitivity and reduces complications of metabolic syndrome
in type 2 diabetic mice - Aging Cell 2022 Aug 19 -
"Rapamycin treatment has positive
and negative effects on progression of type 2 diabetes (T2D)
in a recombinant inbred polygenic mouse model, male
NONcNZO10/LtJ (NcZ10). Here, we show that combination
treatment with metformin ameliorates negative effects of
rapamycin while maintaining its benefits. From 12 to 30
weeks of age, NcZ10 males were fed a control diet or diets
supplemented with rapamycin, metformin, or a combination of
both. Rapamycin alone reduced weight gain, adiposity,
HOMA-IR, and inflammation, and prevented hyperinsulinemia
and pre-steatotic hepatic lipidosis, but exacerbated
hyperglycemia, hypertriglyceridemia, and pancreatic islet
degranulation. Metformin alone reduced hyperinsulinemia and
circulating c-reactive protein, but exacerbated nephropathy.
Combination treatment retained the benefits of both while
preventing many of the deleterious effects. Importantly, the
combination treatment reversed effects of rapamycin on
markers of hepatic insulin resistance and normalized
systemic insulin sensitivity in this inherently
insulin-resistant model. In adipose tissue, rapamycin
attenuated the expression of genes associated with adipose
tissue expansion (Mest, Gpam), inflammation (Itgam, Itgax,
Hmox1, Lbp), and cell senescence (Serpine1). In liver, the
addition of metformin counteracted rapamycin-induced
alterations of G6pc, Ppara, and Ldlr expressions that
promote hyperglycemia and hypertriglyceridemia. Both
rapamycin and metformin treatment reduced hepatic Fasn
expression, potentially preventing lipidosis. These results
delineate a state of "insulin signaling restriction" that
withdraws endocrine support for further adipogenesis,
progression of the metabolic syndrome, and the development
of its comorbidities. Our results are relevant for the
treatment of T2D, the optimization of current
rapamycin-based treatments for posttransplant rejection and
various cancers, and for the development of treatments for
healthy aging" - See
metformin at ReliableRX and
Siromus at ReliableRXPharmacy.
-
MyMD-1 improves health span and prolongs lifespan in old
mice: A non-inferiority study to rapamycin - J Gerontol
A Biol Sci Med Sci 2022 Aug 2 - "In
vivo, a longitudinal cohort of 54 C57BL/6 mice, 19-month-old
at the start, was randomized to receive MyMD-1, high-dose
(126 ppm) rapamycin, or low-dose (14 ppm) rapamycin plus
metformin ... Lifespan was significantly longer in MyMD-1
than rapamycin (P= 0.019 versus high-dose and 0.01 versus
low-dose) in a Cox survival model that accounted for sex and
serum levels of IL-6, TNF-α, and IL-17A. MyMD-1 also
improved several health span characteristics, resulting in
milder body weight loss, greater muscle strength, and slower
progression to frailty. In vitro, MyMD-1 and rapamycin were
compared using a panel of 12 human primary cell systems (BioMAP
Diversity PLUS™) where a total of 148 biomarkers are
measured. MyMD-1 possessed anti-proliferative,
anti-inflammatory, and anti-fibrotic properties. Many were
shared with rapamycin, but MyMD-1 was more active in the
inhibition of pro-inflammatory and pro-fibrotic biomarkers.
Overall, MyMD-1 emerges as a new compound that, even when
begun at an advanced age, induces beneficial effects on
health and lifespan by modulating inflammation and tissue
remodeling" - Note: It's still in trials. See
Siromus (rapamycin) at ReliableRXPharmacy.
- 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:
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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"
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