Initial Personal Observations on Life Extension Methods
I seem to have aged less than many, probably because I
] to stimulate
with consequent elevation of
hTERT protein phosphorylating
and recently I may seem to be younger due to the application of
cyclic telomerase activation
hTERT protein phosphorylation
is required to transport
the hTERT catalytic
component of telomerase
the cellular nucleus
In addition, I found a telomerase-activating
growth factor skin cream
reconstructs both collagen
in the extracellular matrix
TGF-beta is a telomerase inhibitor
so that purely TGF-beta skin creams exist
for a telomerase inhibition
phase of treatment following a telomerase activator
phase of treatment.
This way, collagen
may be reconstructed all the time in the
while lengthening skin cell telomeres in the usual manner with
the application of growth factors
featuring endogenous telomerase activators
Orally bioavailable phytoceramides
can now repair the appearance
of aging skin to provide dramatic facial rejuvenation
[Michael Downey, Life Ext Mag, Nov 2014
Otherwise, I tried and rejected melatonin
a telomerase inhibitor
for daytime use, finally confining it to 1 hour before bedtime [1,2
has been shown to extend
the life span of mice
up to 20%,
although it may promote cancer
at some dosage levels, so I use it at the
of 25 mg before bedtime with
(another telomerase inhibitor
), red grapes, and
I use Centrum Performance
, which includes
for improving cerebral circulation &
and take plenty of vitamin C
as favored by Linus Pauling
], who extended his lifetime.
12,000 and 18,000 mg of vitamin C
every day for years and lived to 93.) Recently (2005) it has become clear that
alpha lipoic acid
should also be taken to cover free radicals
dissolved in lipids, since
only dissolves in water, while
alpha lipoic acid
is soluble in both lipids and water.
Alpha lipoic acid
and acetyl L-carnitine
are taken together,
perhaps also with PQQ
, to combat
age cognitive decline
This should result in
(found in curry powder
should be taken (with black pepper, bioperine
to chelate iron
runaway chain reactions
(see Aubrey de Grey
Free Radical Theory of Aging
in which peroxidized lipids
dramatically accelerate free radical
in the diet catalyzing runaway Fenton reactions
peroxidizing lipid membranes
induce neural inflammation
in experimental animals quite independently of caloric intake. Societies with low iron input (Japanese) or
(India, due to curry in the diet and little sacred cow consumed) have much lower rates of
than America and many other western nations, and show fewer glowing
iron deposits in PET
scans of their brains
I take a tablespoon of turmeric
to improve curcumin
in water frequently during
periods in which telomerase is not to be activated
pills are becoming widely available.
may be taken like pills for antioxidant
red grapes like pills
may be taken for quercetin
It is a good idea to take more
the RDA amounts
to fix methylation
leading to carbonylation of proteins
and consequent problems with Advanced Glycation End products
Finally, I am on a low-calorie diet now that emphasizes
low-mercury chunk light tuna
or mackerel fish
egg whites, fiber, and vegetables rich in phytochemicals,
, and the
Note that mammal flesh heavy with
saturated fats promotes HDL cholesterol and might defeat you
with heart attack
Revenge of the Pets
sink you with
is due to secondary bile products originating in meat fat.
The high methionine levels
in red meat or
eggs may result in high
is degraded by aging [69s]
leading to atherosclerosis
Furthermore, meat, poultry, and eggs contain
that can increase inflammation
increase the stickiness
and gum up the proteasomes
that digest used-up proteins tagged with ubiquitin
is vital to developing youngsters.
Tend to eat foods low in saturated fats and cholesterol
Boiled fish or fish canned
under heat and pressure
and packed in water, on the other hand,
contains the omega-3
good for the fatty sheath around brain cells
Mackerel fish is rich in CoQ10
Perhaps we should be like the star man of NGC 7000
follow the Pelican in the matter of appropriate protein by eating fish.
However, mercury in canned fish
especially in shark, swordfish, king mackerel and tilefish, may be dangerous to human infants.
Chunk-light tuna has less mercury than many other varieties of tuna.
I now try to eat low-sugar, low-glycemic load foods to minimize low-grade
I might add that
(see books on bodybuilding physiology
increase your androgen
levels as well as
especially in the presence of the amino acids
In addition exercise
upregulates many other
endogenous telomerase activators.
There is evidence that treating gum disease
and exercising can both ward off
At 53 (2002), I was still doing pull-ups with 100 lb.
chained on, and did 100 push-ups at 52 .
According to Larry Scott, it takes 20-40 min. of
pumping up to adequately increase
HGH levels, so I use a split routine
about 40 min to an hour each day, taking several days to cover my whole body.
Incidentally, I also used alpha-hydroxy in Pond's
Age Defying Complex to grow new skin cells,
but am switching to a
CoQ10 skin cream
that will clean out cellular wastes,
antioxidize cells, remove
and not reduce the number of cell divisions available to my
Perhaps a future
L-Carnosine skin cream
Resilience Rescue) could even extend the number of cell divisions available
This might also be accomplished with a skin cream
in glycerin or liposomes applied
in a month-on, month-off periodic manner for a year. Most recently in
May 2013 I have been using
growth factor skin creams,
in particular telomerase-activating colostrum skin cream,
which also contains TGF-beta.
Telomerase-inhibiting TGF-beta skin cream
can be used to reconstruct collagen and
in the extracellular matrix
during telomerase inhibition periods. Thus
elastin can be
restored all of the time, throughout both halves of the cycle in
cyclic treatment with
telomerase activators and
Finally, it has become clear that crushed garlic
[List], a splendid
antibiotic and with
one of the "lillies
of the field",
is also a Hayflick Limit extender for dermal fibroblasts.
Diallyl disulfide from garlic
penetrates the entire body like a HDAC inhibitor gas,
expanding chromatin to improve transcription of proteins such as
Note that onions inhibit
due to their benfotiamine,
speed up nerve conduction velocity,
and tend to lengthen dermal fibroblast telomeres via their
By 2013, we have supplements and techniques for
reversing cellular senescence itself
and restoring senescent cells from states
formerly believed to be irreversible.
Exercise with consequent high levels of
down-regulates FOXO genes and
caveolin-1, modifying the cell membrane of senescent cells
to restore the youthful phenotype of the cell and
communications with growth factors such
EGF and PDGF
(both components of colostrum) that restart the cell cycle and
Cyclic AMP is made by adenyl cyclase from ATP that can be boosted
with creatine monohydrate during
Cyclic AMP can also be boosted with forskolin.
Exercise will continue to be available with
vitamin D and
vitamin K2 supplements such as
to prevent arterial calcification and aortic stenosis,
and homocysteine blockers available from B-vitamins
to prevent artherosclerotic plaque.
Tocotrienol-rich fraction from palm oil with alpha-tocopherol and
alpha, beta, delta, and gamma tocotrienols helps to restore senescent dermal fibroblasts to their youthful phenotype.
In addition, we can down-regulate p16INK4A,
which makes recovery from the senescent state more difficult,
by eating carrots, by using retinol skin creams, and by exercise. Since P16INK4A is a ubiquitinated
protein removed by proteasomes, down-regulation of P16INK4A can cause it's levels to decline substantially.
An Optimum Anti-Aging Program
Dosages: [62s] and
Medicines and Dosages 2013
Free Radical Defense for Cell Membranes and DNA with Antioxidants, Anti-Glycating Drugs, and Diet
See my medicine program for May, 2013 with photos.
I am beginning to suspect that the ideal anti-aging program uses
Vitamin C with
perhaps from 1000 mg C per day up to the Linus Pauling maximum dose of 18000 mg per day, in which case
bioflavonoids reduce any
overdose effects of
Vitamin C on
white blood cells.
Dr. Al Sears claims that 500-1500 mg of
vitamin C, taken twice a day,
helps to preserve telomere length in mitotic cells,
which is accelerated by free radical damage
However, it is clear that cyclic telomerase activation
is required to implement telomere rejuvenation resembling
time travel backwards in time.
Grape seed extract
helps Vitamin C
cell membranes better.
I get my grape seed extract now in a
Solaray brand of
grape seed extract
and red wine extract
and take 2500 mg of vitamin C every day.
(a telomerase inhibitor and
should be taken with a source of quercetin
like onions, apple slices, or red grapes to improve
probably with chunk light tuna to provide NAD
which enables its sirtuin-activating properties.
This will retard the shortening of the
genetic clock telomeres
in the nucleus that cause nuclear DNA aging
High-gamma Vitamin E
to ensure peroxynitrite quenching)
and perhaps R-dihydro
lipoic acid or alpha
lipoic acid should also be taken to cover
free radicals dissolved in
vitamin C only
dissolves in water, whereas
alpha lipoic acid is
soluble in both
lipids and water.
This should result in superior protection for
mitochondrial DNA and
cellular aging due to mtDNA aging
These days I get about 1000 mg of
alpha lipoic acid daily,
which also effectively opposes the formation of
Advanced Glycation End products
the formation of free radicals.
[Index] 500mg with 200mg
Alpha Lipoic Acid
three times a day fights cell sugar damage
(glycation of proteins),
improves neurite growth,
improves mental energy,
and iron-chelating curcumin
is a "Sirius" anticancer star, but today I also
get plenty of anticancer odorless
(a telomerase inhibitor) and garlic oil,
and am worrying about how garlic may be taken otherwise.
Heavy metals like mercury from
fish or your fillings should be chelated with
N-acetyl-cysteine (NAC), curcumin, or
perhaps with carnosine.
The antioxidant preservative BHT
recommended by Dr. Denham Harman helps mice to live 45% longer, so perhaps we should
consider using it
In addition, one should also take broccoli sprouts
to combat cancer and
tumor formation with
I get lots of broccoli with
indole-3-carbinol in salads and
broccoli sprouts rich in
at least once a month.
One should take a
like CENTRUM Performance
daily to supply essential vitamins and
like selenium shown to
be effective in cancer suppression.
It takes one atom of selenium to form the cytoplasmic kind of
superoxide dismutase (SOD)
Selenium is also
found in the endogenous antioxidant
and is of course required for its synthesis in the body.
Another cytoplasmic kind of superoxide dismutase,
CuZnSOD, is formed by an
atom of copper and an atom of zinc.
The mitochondrial type,
MnSOD, is formed by an atom of
Supplements featuring bioavailable
such as wheat sprouts [64s],
GliSODin may be taken with mind-sharpening
SOD-boosters such as nootropic
or Deprenyl .
Furthermore, calories should be restricted by the reduction of
high-sugar foods and high-glycemic load foods
Try celery for breakfast, or celery with cooked tomato paste
to get plenty of lycopene in to guard against
and avoid the meat fats giving rise to the carcinogenic
secondary bile products that cause it by nourishing
fatty acids from
fish and fish oils
good for your heart should be substituted for
omega-6 fatty acids.
DHA is brain food, and it is best to get it in
pure form, since the EPA in ordinary
fish oil raises your triglyceride levels.
The sulforaphane in
selenium in CENTRUM,
the resveratrol and
red grapes, and the capsaicin
in red chili peppers will help prevent
cancer complications involving cells
that we want to preserve at robust length.
Greater-than-RDA levels of folic acid and
B-vitamins such as
trimethylglycine should help deflect
and glucose toxicity in
glycation and block
leading to atherosclerosis
[Books], the lipid soluble-form
of vitamin B1,
is found in trace amounts onions
(also rich in quercetin), so I wolf down an onion sandwich
every day. (Be sure to mind your breath spray while you're at it.)
Using a benfotiamine pill
for a dose of 100 mg or more is preferable to taking trace quantities of it found in
onions, garlic, shallots, or leeks.
Also, pumping up via weight lifting every day using a 3-day split
routine to cover the entire body increases the
HGH human growth hormone level, and stimulates
the pituitary gland
or the pineal gland
into behaving as if you are a useful specimen that ought to be preserved.
It's best to take whey protein
to enhance your HGH levels,
and to get micronized creatine monohydrate for
quality muscle contractions.
Include an amino stack to optimize HGH,
which opposes cortisol,
an aging accelerator
we must foil with HGH and
To this you may add other
antioxidants such as
vitamins A and
blueberries with other
dopamine enhancers like
Deprenyl for your
brain, and other phytochemicals described below 
(from turmeric, and with black pepper added to improve curcumin
grape seed extract,
garlic, red grape skins,
pecans, walnuts, tomatoes, spinach, and red chili peppers.
I use a low-fat blueberry yogurt with plenty of
whey protein in it that is just 80
calories per cup, delicious, and full of
To this I add a 3-tablespoon chilled
cocoa powder in water drink daily for
(a PQQ supplement would be better),
and flavonols, remembering how chocolates were used by super centenarian
Madame Jeanne Louise Calment
for effective life extension.
Like Jeanne, I go over my skin with extra virgin
olive oil frequently, and get plenty of cooked tomato paste
to up the antioxidant
Raspberry seeds and mixed nuts contain
ellagic acid and should be taken.
The polyphenol resveratrol
found in red grape skins has been shown
to increase the lifespan of yeast, worms, flies, and no doubt of 122 year old aging record holder
Madame Jeanne Louise Calment,
so eat red grapes and supplement your intake of
(a telomerase inhibitor and
SIRT1 activator) improves
so take it with quercetin-rich apple slices or red grapes.
Madame Jeanne Louise Calment was also fond of her
, containing the powerful
compounds squalene and oleic acid, so take more olives and
olive oil with antioxidant
lycopene or tomato juice.
Extra virgin olive oil has fewer toxic
impurities than cooked olive oil, and since olive oil lowers LDL and raises HDL
it is the optimum component for salad dressings.
Just add the spices and hold the vinegar,
as it does not help the antioxidant problem by making your
pH more basic.
The polyphenols found in green tea
[25a] may also be responsible for long lives,
so take it, but never on an empty stomach.
Not eating mammals will reduce the level of cholesterol
deposits on the inside of your veins and arteries by
reducing toxic homocysteine
levels due to incomplete methylation of methionine from red meat
might be taken instead to improve
methylation without generating a lot of
I think tuna fish or mackerel fish with favorable
omega-3 fatty acids should be substituted for mammal meat,
such as Salmon, Herring, Mackerel, and Bluefish.
Remember, your blood pressure goes up as the inverse of the fourth power of the inside radius of your
veins and arteries, and we need to prevent
heart attacks from this source
(aggravated by vasoconstrictive smoking),
as well as from hypertension due to high salt levels or
nervous stress associated with high cortisol levels.
Cooking eggs in sesame oil lowers blood pressure
partly via its sesame lignans.
Some skim milk each day can provide the 9 essential amino acids
casein, the principal protein in milk,
from which the rest of the 20 or 24 (L.Pauling) important amino acids may be synthesized internally.
This also provides calcium to guard against old age shrinkage ,
which also requires vitamin D and
Separate taking skim milk from eating dark chocolate
by at least an hour ,
as milk interferes with absorption of
chocolate polyphenol antioxidants.
Soy protein food products and
soy isoflavones have many benefits,
and tending to prevent cancer,
high blood pressure,
metabolic syndrome, and
type 2 diabetes.
25 grams of soy protein per day
(20-90 mg of soy isoflavones)
is an effective dose for lowering cholesterol.
Soy milk comes in many flavors and without solid bulk is quite slimming.
(However, 1/2 gallon soy
milk per day for 2 days can cause constipation and burning urinary tract that
would be worrisome to a dog.)
Eat the world's healthiest foods and understand their properties
and compositions. (See
Linus Pauling on Micronutrients.)
, shown to be effective in anti-aging medicine,
should be taken before bedtime only at up to 25 mg/dose.
Experimenters found that mice fed extra melatonin
lived 20 percent longer than control mice.
Curcumin mixed with black pepper to improve
should also be taken for its
excellent neuroprotective and anticancer properties.
Otherwise, pre-rinse teeth before brushing with
antiplaque mouthwash to prevent build-up of tartar
and ward off inflammation associated with
Alzheimer's disease ,
brush with an anticavity and whitening fluoride toothpaste like Ultrabrite to prevent tooth decay,
spit it out, then use a remineralizing and
enamel-hardening mouthwash, which keeps the teeth in an environment with the pH > 5.5, preventing the
deminaralization associated with dental caries.
Floss at least once a day to clean the proximal
surfaces of teeth, and be sure to brush all tooth surfaces.
A whitening mint mouthwash can be used to finish for a brighter smile, an objecive also served by
whitening toothpastes, whitening strips, and tooth-bleaching treatments.
Use an age-defying skin cream with
astragaloside IV to fight
and cellular wastes in your skin.
Grape seed oil also helps with lines around the eyes.
Note that Ubiquinone
lipofuscin (waste buildup in the cell),
a cellular senescence
mechanism distinct from telomere shortening.
Wastes associated with lipid peroxidation
accelerate free radical damage and should be
flushed out with
I find DMAE inexpensive and take
300 mg/day when I can to work on the cellular aging mechanism involving
cell membrane penetrability to potassium.
widely available as the health food store supplement
(coenzyme Q) and
probably should be taken to cover for lipofuscin
which gradually turns your heart black as time goes on.
The new super bioavailable
CoQ10 is about 8x better milligram per milligram.
As I recall,
CoQ10 tags a glycolized protein
lipofuscin waste molecule with 3
so that the waste molecule is excreted by the cell.
can also be used to undo protein glycolization that results from
 to proteins.
Both CoQ10 and
Acetyl L-carnitine are
substances normally found in the body and both improve your mental energy
and perceptual focus.
Acetyl L-carnitine plus
alpha lipoic acid
is sometimes prescribed.
Studies showed that old rats behaved like young ones then.
(Alagebrium) has also been proposed as a
cure for glycolized proteins.
Finally, chromium picolinate can supply
a chromium molecule essential for the cleaving of
insulin, and has been shown to increase the life span
of laboratory mice 15%.
However, there are fears it can be dangerous to DNA and that it is mainly good for loosing weight.
In any case, a low-glycemic load, low-sugar diet is preferred to deflect chronic low-grade
Perhaps at least 500 mg per day of carnosine
a naturally-occurring substance in fast-twitch muscle fibers
present in red meat, poultry, and fish, should be added to this program.
High doses of carnosine can be taken,
up to 500 mg per kg of body weight in a single serving without toxic effect.
Some authors recommend 500mg to 2000 mg per day,
and I suspect 500 mg every three hours would be best,
although this more than most of us can afford.
Additional anti-aging therapies should be considered.
A homocysteine screen including TMG
will not only protect you against atherosclerosis,
but will help preserve telomere length, like the
antioxidants on our list.
against Parkinson's disease and other
but NSAIDS can also cause ulcer problems, so I am not taking them.
Inflammatory COX-2 enzymes can be inhibited
with curcumin in turmeric
or from gingerols in
ginger without hitting the stomach-protective
might also be an effective substitute for
NSAIDs, which can cause
if they inhibit COX-1 like
Old age diseases
such as macular degeneration
 can be guarded against by taking
zeaxanthin, found in
orange juice, egg yolks, lettuce, and
along with a homocysteine shield to stop associated
Some curry powder, curcumin, or turmeric should be taken
(with black pepper to provide piperine for improved
curcumin bioavailability) to chelate copper and iron and head off
and cancer (12).
Alpha Lipoic Acid
may be the best commonly available thing for
and I get my inexpensive brand of it from Wal-Mart these days.
Another important drug in
is definitely ubiquinol
the new "super bioavailable CoQ10" eight times as
bioavailable as standard
To repair hydroxyl-radical damage to cell membranes,
I use DMAE, and am considering
which is more expensive and more difficult to obtain in the USA.
A phospholipid exchange using
is also a promising route to cell membrane repair.
Protecting Aging Cardiomyocytes & Vasculature
Cardiomyocyte aging of
heart muscle cells
is perhaps best repaired using ubiquinol
(Life Extension's super
pomegranate juice or extract,
bilberry extract, and
alpha lipoic acid
in combination with a low-calorie
including a good deal of
together with a program of healthy exercise and plenty of
begin to converge toward the end of a lifetime,
while the primary earlier cause of death
seems to be cancer.
Also, I note that Geron
and vasculature as benefiting from pulsed-on-then-off
treatments [81s] featuring
or other telomerase activators.
Note that these treatments are facilited in difficult tissues such as mesenchymal-derived
connective tissues by including
(such as lactates from pumping up with weights)
to expand chromatin for transcription of
Vitamin C to prevent degeneration of
collagen, a low-sugar diet with
vitamin B1, and
and turmeric with
curcumin to prevent
Fenton reactions should help prevent
degeneration of heart tissue, which should also be protected by avoiding
alcohol, which promotes
deposits, and by avoiding the smoke of cured tobacco, browned poultry skins, and other food browned by
the Maillard reaction,
all of which import fully-formed advanced glycation end products
strengthens capillary walls, and fortifies the brain against
in addition to protecting
vasculature in the heart.
We also take 4-6 grams of L-arginine
[Links] per day with 1 gram of
[Links] (found in watermelon rind)
to generate nitric oxide (NO) from
nitric oxide synthase
from bodybuilding exercises for maintaining the heart,
following Nobelist Dr. Louis B. Ignarro's program outlined in
NO More Heart Disease.
may be taken to protect
the cell membrane against peroxynitrides.
In addition, one takes the 4 antioxidants
alpha lipoic acid,
and vitamin E.
helps maintain the NO
supply for a longer period of time than results
from the use of L-arginine
alone, allowing NO to reach more cells.
From studies by Vasa and Hayashi
[Vasa, et al., 2000,
Hayashi, et. al, 2006], we recognize that
lengthens telomeres in the vascular
rejuvenating senescent cells there,
tending to deflect heart attack,
This can also rejuvenate the thymus gland,
allowing it to produce fresh T-lyphocytes.
On the other hand, [Erusalimsky JD, 2009]
indicates that NO
activates SIRT1, not telomerase,
to perform it's life-extending tricks, a contention
also supported by
Hong Y, Quintero M, Frakich NM, Trivier E, Erusalimsky JD, 2007].
However, Vasa and Hayashi measure NO-associated telomerase activation.
Vitamin D [Index,
Links/vitamin D and telomere loss,
attenuates telomere loss rates in leukocytes and many other cells. However, it is a
that might interfere with a telomerase activator
if taken at the same time.
According to William Falloon of Life Extension Magazine,
men with low vitamin D levels suffer 2.47 x more heart attacks.
He recommended 1000 IU per day, which is inexpensive. Today, we use perhaps 5,000 IU per day.
A 142% reduction in heart attacks
was seen with vitamin D.
Women deficient in vitamin D have
a 253% increased risk of colon cancer, and women with the
lowest level of vitamin D
had a 222% increased risk of breast cancer.
Men with higher levels of vitamin D have a 52% reduced
incidence of prostate cancer.
vitamin D also helps prevent
Chromosome Reconstruction with Telomerase Activation and DNA Repair
Product B (6 caps/day, 3210 mg),
TA-65 (4x8 mg/day),
cycloastragenol (25 mg/day), astragalus root (33 grams/day), and/or a selection of other
may be used to reconstruct short telomeres
with cyclic telomerase activation.
See Quick Summary for my present program involving a selection of safe
telomerase activators performance-enhanced by
conservatively chosen HDAC inhibitors.
Endogenous telomerase activators, especially
exercise-induced telomerase activators,
may be used and boosted with supplements.
The people's small molecule telomerase activator
[81s/6b, List] is
Astragalus Root Extract in glycerin
(1 mg astragalosides/30 drops), taken at greater than 5 mg of
per day (> 150 drops/day), two weeks on and two weeks off, continuing over the course of a year, with
2 grams of chitosan to improve
According to recent Chinese experiments
on Beagle dogs that could tolerate 2.85–19.95 g/kg, we suspect that quite large doses of
Astragalus Root Extract may be taken.
Alternatively, I take at least 6 x 200 mg
Astragalus Root Extract
capsules per day for 15 days
of the month to get > 5 mg
per day during the "on" part of the treatment cycle.
Presently I take 66 capsules (33 grams/day) of
Astragalus Root, available from
Whole Foods and many
other stores at $5.90 for 50 grams per bottle.
Note that smaller doses of astragalus root extract
are used to deflect virus infections
by activating interferon,
while we are trying to induce transcription of hTERT mRNA with higher doses of the same medicine.
During the first two weeks of each month on one must avoid
[81s] such as
EPA, applying them during the next two weeks.
Since a high-polyphenol diet can produce
telomerase inhibitors, during the first two weeks of
each month I recommend a low-polyphenol diet during that period.
This keeps the cost at about what it was before using
List] to re-extend your telomeres
to repair the tip-ends of your aging chromosomes
Cycloastragenol at 25 mg/day
is probably superior in such a program, and cycloastragenol,
the common structural element in the astragalosides,
is readily available at this time in TA Sciences
Iron Dragon cycloastragenol,
and RevGenetics Astral Fruit NF.
Note that the astragalosides
improve wound healing, and that
activation of stem cells can restore their ability to proliferate.
Finally, the DNA repair enhancer
Cat's Claw extract
is available and some months I can take it
for about $10/month in the 2nd part of the month's
telomerase activation on-off cycle.
I am still doing without the
chromatin remodeling factor
sodium 4-phenyl butyrate
to maybe stretch my telomeres, but I may try it later.
[Images] is available now in pill form
hTERT transcription from the butyrate-expanded chromatin,
but L-carnitine and lactates from pumping up with weights are still safer
HDAC inhibitors for chromatin expansion.
which lengthens the life span of Drosophila, may also be used to expand chromatin for transcription.
Supplementing magnesium may help
telomeric DNA helicases work better to maintain telomeres, and
definitely helps lower blood pressure.
Opening Telomere T-loops for Telomerase Repair and Application of Novel Activators
It has become clear that niacinamide
(nicotinamide) improves the expression of
a telomeric PARP
the telomere t-loop closure protein
allowing it to detach from the telomere loop,
so that the loop can open and provide access to telomerase.
Up to 1 gram/kilogram of niacinamide
has been given to experimental animals to
boost their tankyrase 1 levels,
but the recommended human maximum dose is < 3 grams/day, so I am considering trying
nicacinamide in that range.
It rarely causes side effects.
I am taking nicinamide in the morning to develop adequate levels of NADH for
poly(ADP-ribo)sylation of TRF1 in the evening,
and to dimenish niacinamide strength in the evening,
because niacinamide itself can interfere with the action of
PARP enzymes such as tankyrase 1.
Upregulating telomerase expression continuously has been
observed to lengthen telomeres.
Niacinamide is often taken at 1x or 2x 700 mg/day.
Niacinamide-treated dermal fibroblasts at 5 mM niacinamide
showed 75 population doublings at 25 mM glucose, and 83 population doublings at 5.5 mM glucose,
with excursions to 125 population doublings at normal glucose levels according to
et al., 2006.
The canonical Hayflick Limit for such cells is 49 population doublings.
The earlier cells were treated with
niacinamide, the more their life span was
extended. Furthermore, tankyrase 1
may become active for removal of TRF1
by phosphorylating tankyrase 1
Therefore, the telomerase activator
diosgenin contained in
Fenugreek seeds and Fenugreek extract (which
activatates production of the
HIF-1 transcription factor for hypoxia) becomes attractive,
because it also contains
which increases insulin secretions.
Insulin secretion boosting
is best limited to after a workout, which also boosts levels of
heat shock proteins that
transport telomerase activating factors into the cellular nucleus.
Therefore, Fenugreek seeds or extract
and any other telomerase activators
should be taken near the conclusion of an evening workout.
should probably be taken at < 10 grams 30 minutes to an hour prior to workout
along with L-lysine
at 1500 mg to boost HGH levels and
dilate blood vessels for transport of these factors to cells.
Furthermore, Nitric Oxide (NO) from
arginine prior to the workout
activates telomerase in
as it assists with transport.
which should also be taken prior to the workout,
darkens hair and
so that androgen-sensitive cells such as
heart muscle stem cells
and hair follicle melanocytes
experience telomerase up-regulation.
These measures should be
introduced during the first 15 days of the month,
when telomerase is to be upregulated to lengthen telomeres, before applying
for 15 days to maintain anticancer defenses.
Telomeres stained purple for FISH,
Fluorescent In Situ Hybridization.
QFISH technique measures the brightness of
the purple dots to measure telomere length.
Looking Out for Number One.
Future Treatment Possibilities
Just how future treatment for aging might work using the enzyme
to controllably lengthen telomeres in dividing, mitotic cells has
become clearer lately.
One at first envisions Dr. Jekyll downing a test tube full of it, or injecting it into the body,
but such a large molecule will not cross
the blood-brain barrier
nor pentrate directly into cells, except perhaps
from cationic transfection reagents
and taken into the cell by
This a method for inserting DNA plasmids
has announced small-molecule
is available from TA Sciences
including many telomerase inducers promoting
transcription in dermal fibroblasts and other cells.
Institute of Bioregulation and Gerontology
a small 4-amino acid peptide chain protein made from
, so that
telomerase need not be taken and
across cellular membranes
Instead, one will swallow, inject, or sublingually ingest
under the tongue.
Alternatively, telomerase activators including hTERT transcription inducers can be applied transdermally in
or in colostrum
which features telomerase-activating
human growth factors
can be made to yield 14 different
endogenous telomerase activators
separately boostable with nutraceutical supplements.
root (at < 33 grams/day)
least likely to be associated with cancer
than alternatives that activate telomerase (7)
In particular, IGF-1
(Insulin-like Growth Factor 1
(Epidermal Growth Factor
may be used, but to inhibit cancer
one may take extra Vitamin D
extract at a disjoint time when using
Bear in mind that
a telomerase inhibitor
that should not be taken together at the same time with
Targeted Genome Editing with Adenovirus Transfection
Most older proposals [66
] featured injection of a nucleic acid complex
or a plasmid
into the cell,
or using a "viral vector"
to permanently promote the expression of telomerase in cells to lengthen telomeres.
For this gene therapy
to work, the viral vector
had to integrate the hTERT gene
the catalytic component of telomerase like
into the host cell DNA at some point.
This is gene therapy technique
possibly using adenovirus transfection
which always integrates the
at the same place.
On the other hand, lentiviruses
DNA into random locations
in the genome
, and are more likely to cause
It so happens that hTERT
may be transfected
for gene therapy
Targeted introns may improve control of gene expression
Sendai viral techniques
may also be useful for our life extension application
as well as other viral vector methods
Dr. Michael Fossel
also mentions possible dendrimer
and transcatheter application techniques
in his 2004 textbook
and Human Disease
, and points out that high-pressure
commercial gene guns
] may be employed on the skin
See also plasmid
Targeted Genome Editing with AAV Adeno-associated Viral Transfection
Also, it seems that AAV adeno-associated virus transfection
with artificial genes
featuring (say) hTERT
promoters with DNA code
for peptide bioregulators
epithalon peptide (Ala-Glu-Asp-Gly)
might be useful in
genome redesign for
mild by comparison with adenovirus transfection
and always integrate into the human genome
at the same site AAVS1
Targeted Genome Editing with Zinc Finger Nucleases
Another emerging possibility in
targeted genome editing
zinc finger nucleases
insertion of DNA code into the genome
at a wider variety of sites.
Zinc Finger Nuclease Technology
Targeted Genome Editing
is ready to go from
Aldrich/Zinc Finger Nuclease Technology
can be assembled from Sigma Aldrich standard components
to fit gene patterns.
A pair of zinc finger nucleases making up
catalytically active FokI dimer
functions like scissors at a specific site in the mouse, rat, or human genome
can be packaged with a DNA repair template insert (with overlapping hybridizing DNA wings) including
a desired gene sequence and delivered to the cell by
cationic transfection reagents
This strips the genetic sequence one specifies into
where one wants it to go.
You just order it up from Sigma Aldrich
and they will send you the package to do the job.
They also supply
gene knockout packages
and other gene-task packages
For instance, they have one that integrates a
from a liposome
into the AAVS1
] site where the
AAV adeno associated virus
integrates into the human genome
There are indications that the human genome
can be painlessly modified using plasmids
On the other hand,
may be used to prepare genetically modified cell cultures or modified blood fractions.
Finger Nuclease technology
you might strip a gene into your own genome
or MnSOD, or to install an extra copy of
to stay young with,
may be available now to be
applied by transfection or electroporation with subsequent transfusions or stem cell transplants.
Also see Nucleofection
and Sangamo Biosciences
The advantage of using a transfection
technology such as
zinc finger nuclease
permanently impacts the genome to obtain anti-aging effect may include reduced expense
over the course of treatment.
Plasmid Transfection Gene Therapy
Alternative methods, such as a liposome transfection
mechanism for plasmid
, have been specified.
to be transfected
are transported in
cationic transfection reagents
available from a variety of firms, including Invitrogen
Michael Fossel suggested using C-myc plasmids
for activating hTERT
, since there are several sites for
on the hTERT promoter
For other possibilities (such as hEST1A, also called EST1p
) based on plasmids
including genes improving hTERT performance in telomerase synthesis, see
copy number increases during exposure to a
and decreases after the vector removal.
In one case, HeLa cells
were incubated with a
cationic liposomal vector for 24 h.
EMA-pGL1 plasmid entry was detected by
At first we see increasing fluorescence intensity distribution during exposure to the liposomal vector.
Later we see decreasing fluorescence intensity distribution after removal of the
at 24 h,
presumably due to EMA fluorescent label
resulting from cell division."
Wen-Chi Tseng, Frederick. R. Haselton and Todd D. Giorgio (1997),
Transfection by Cationic Liposomes
Using Simultaneous Single Cell Measurements of Plasmid Delivery
and Transgene Expression
Journal of Biological
This means that
transfected via cationic liposome technology
as cell division
continues, so that repeated application synchronized to cell division frequency may be useful in medical treatment
See Srinivasan C, Siddiqui S, Silbart LK, Papadimitrakopoulos F, Burgess DJ. (2009),
Dual Fluorescent labeling method
to visualize plasmid DNA degradation
For another relevant paper, see Liu Lei, Li Xinyu, Zhu Xuefei and Li Guigang (2005),
Cationic liposome-mediated bcl-xl
gene transfection into human keratocytes
of Huazhong University of Science and Technology
Volume 25, Number 3, June, 2005.
schemes may fail to permanently impact the genome and
require many repeat runs to be effective, so that the total cost of therapy with
targeted genome editing
zinc finger nucleases
may be less.
Stem Cell Transplants with Transfected Cells
and other firms have worked out procedures for
cell lines using liposomes containing plasmids
For instance, see the Invitrogen
NEON transfection system
which is applied to the electroporation
of liposomes bearing plasmids
into various in vitro
cultures of cells such as dermal fibroblasts or T-cells.
This method might be used to prepare rejuvenated adult stem cells for stem cell transplant operations.
See hTERT plasmid sources
Protein Targeting Telomerase to Cell Membranes
However, Phoenix Biomolecular
specified a cell penetrating peptide scheme
to deliver the enzyme telomerase
directly to cells.
This may be done using the transport tagging mechanism that the cell uses in
to organelles, which is
also used in some cases to
target proteins to the
exterior cell membrane
It is also possible to transport proteins into cells though the cell membrane inside
cationic transfection reagents
(Debs et al. 1990).
Furthermore, RNA may be transfected into the cell by this technique (Malone et al. 1989; Wilson et al. 1979).
See liposome endocytocis
On the other hand,
transfer of antisense telomerase RNA
is used in cancer therapy.
liposomal transfer of hTERT mRNA
would be useful in rejuvenation
. I note that
used for transfection, so that aerosol liposome rejuvenation of the lungs may be done.
In old China it was noted that astragalus users sometimes lived until they finally died of whooping cough.
Also, Christopher M. Counter and Blaine N. Armbruster
specified a telomere elongation
published in 2007 that identifies a
fusion protein deliverable in liposomes
and otherwise to
POT1-hTERT fusion proteins
liposome delivery of POT1-hTERT fusion proteins
I note that a reverse transcriptase
is used to reprogram DNA, that the enzyme telomerase is such a reverse transcriptase, and that
applies them at random sensitive points in the host DNA
using techniques involving viral vectors
which is always less safe and straightforward than applying a small
molecule telomerase activator
like epithalon peptide
tricostatin A (TSA)
new TA-65 from Astragalus
to promote transcription from the existing hTERT gene
Telomerase Delivery by Nanoparticles
There is also the patent
Delivery by Biodegradable Nanoparticle
, that was developed by
The patent describes nanoparticle design for slipping hTERT through
cell membranes, and moieties for targeting nanoparticles to different tissues.
Note that it may be
necessary to phosphorylate hTERT
conveyed into the cellular cytoplasm by this method, so that it can be
transported into the nucleus.
This may be done using AKT1 kinase
via application of
, which can be provided by
is produced from HGH in the liver.
Telomerase Activation with Natural Hormones
Dr. Don Kleinsek
indicates that a hormone may be used to induce telomere lengthening
and growth hormone
hTERT transcription in hamster ovaries and rat liver cells
improving the number of hTERT mRNA transcripts and
indicating that Human Growth Hormone
may be used to lengthen telomeres.
Note that 17-beta-estradiol (estrogen
are hormones that activate hTERT transcription,
although they are associated with feministic transformations.
is inexpensive and
very effective as a telomerase activator for
post-menopausal women and she males.
It is used like a synthetic progesterone
Perhaps a cyclic program of application including androgens can be used to allow
men to get some telomerase activation milage from
without introducing undesired transformations.
fenugreek extracts feature life-extending telomerase activation and
may be used to produce feministic transformations or not,
depending on how they are applied.
Most human growth factors
turn out to
activate hTERT transcription in various target tissues.
, produced from
in the liver,
activates telomerase activity by
in the cytoplasm
for return to
the cellular nucleus
and may be the Kleinsek-specified
Conversely, an antagonist of growth hormone-releasing hormone
was observed to dramatically decrease telomerase activity
Perhaps in the future one will consume whey protein
which boosts HGH
prior to a bodybuilding
workout also supplemented by HGH-boosting amino acid stacks or
[Links/amino acid HGH Boosters
in order to lengthen one's telomeres using readily available medicine, equipment, and procedures.
I am still struggling to fully research these and other advanced techniques.
Measuring Telomere Length for Process Control Feedback
Whatever is done, it seems clear that effective
or therapy to
retard telomere shrinkage
will require methods for measuring the telomere length
or some other advanced technique, such as endonuclease cutting of telomeres with subsequent
polymerase chain reaction
(PCR) gene fragment amplification of the telomere tails and then gene
sequencing to obtain telomere length with single nucleotide resolution, rather than the Southern analysis method
using electrophoresis on a gel prepared with telomere fragments obtained
by the use of an enzyme on a larger quantity of tissue.
in Situ Hybridization (FISH)
and TA Sciences
offer measurements of telomere length
for feedback supporting programs to activate telomerase with
Telomere Elongation with 5'-TTAGGG-3' Oligonucleotides
It has been discovered that strings of [5'-TTAGGG-3']n
patched on to telomeres to lengthen them just by supplying them in the environment.
Researchers are working at synthesizing such
Perhaps it would do to merely supply [5'-TTAGGG-3']n
sections in solution
or inject them into the cell inside
Something similar was proposed by
Michael D. West
Woodring E. Wright
in 1997 in their US Patent
Methods and Reagents for Lengthening Telomeres
Their patent prescribes making available to the cell
typically including at
least 2 to 3 telomeric repeat sequences, which in humans is 5'-TTAGGG-3', or 5'-GGTTAG-3', based
on the hTR
Perhaps telomere enlongation
by orally bioavailable oligotide liposomal spays or liposomal skin creams will furnish suitably rapid rejuvenations.
The oligotides themselves may be prepared by
from samples isolated from our own DNA or
prepared by DNA synthesizers
, or isolated from
using methods familiar from
recombinant DNA technology
and genetic engineering
Also, the RNA oligonucleotide UP1 = UAGGGU
has been observed to enlongate telomeres.
Telomere Enlongation with Rolling Nanocircles
Similarly, nanocircles of AATCCC repeats complementary to
telomere 5'-TTAGGG-3' repeats
may be used, as proposed by
nanocircles for telomere repair
Discovering Telomerase Activators with High-Throughput Screening
(defunct) investigated natural proteins known to enlongate telomeres
is also investigating antiaging
telomerase activation technologies, and claims to have discovered hundreds of
using high-throughput testing
The problem then is to measure the associated rates of
telomere reconstruction in base pairs per year (say 460 bp/year = 9 years/year rejuvenation rate),
the mode of action of the telomerase activator or hTERT transcription inducer,
the comparative effectiveness of the activator for each type of human cell,
the safety of the medicines, and to determine side-effects and safe use guidelines.
Other Mechanisms and Alternatives
exist to lengthen telomeres without telomerase
One writer has proposed using a
viral vector procedure
to turn off telomerase expression entirely, then replace worn-out cells with
featuring telomeres lengthened by
Without the stem cells
however, this would lead to damaged tissues and/or
It seems clear that excellent feedback on telomere length will benefit research into methods
for lengthening the telomeres, and may be required in the course of
cyclic anti-aging treatments
The muscle cells
do not divide, although they have
stem cell progenitors
] that do go through
stem cell mitosis
The telomere-lengthening procedures are most important for the
mitotic cells of the body
including the skin cells,
the white blood cells, and also for the cells of the lining of the colon
that finally stopped Dr. Linus Pauling at 93 and that will stop us
if we don't fix them by lengthening their telomeres.
It is like a fuse burning down to a ball.
These cells can divide 50-100 times before using up their telomeres, which are typically from 4,000 to
15,000 base pairs long, about 1/10,000 the total DNA in the gene.
Typically 20-50 telomere base pairs (bp) are used up per cell division, depending on the cell type
However, recent studies have shown shortened telomeres in
, and studies using telomerase to
restore youthfulness to old neural tissue
in culture are in the works.
Thus some sort of telomerase treatment or telomere-lengthening procedure may be applied to a wider range of cells
than the skin, the white blood cells, and the colon in the struggle to overcome
, be it
premature stress-induced senescence
or replicative senescence
Indeed, the problem of obtaining
post-mitotic cell life extension
by preventing cellular garbage formation
) by free radical action catalyzed by
or by cleaning cellular
garbage out of the cell is a major focus of development.
To live 5000 years may require applying something like
meristematic stem cells
as in bristlecone pine, or at least rejuvenating our internal supply of stem cells with
hTERT transcriptional activators
supplements promoting kinases for
We may take medicine to propel adult stem cells from the bone marrow out into circulating blood,
extract the blood, then externally telomere-extend them with telomerase activation, sort them from the
blood, freeze them, and eventually treat them to have properties
more resembling embryonic stem cells, as has been done with mice before they are re-implanted as desired.
Since telomerase activation enables stem cell proliferation, we may improve the proliferative abilities
of our stem cells by taking small molecule activators such as the
, equipping ourselves with continually
rejuvenated stem cells rivaling the meristematic stem cells of the bristlecone pine.
It should be generally useful to monitor crucial biomarkers
] in a systematic program to treat aging.
For more on the medicines used to treat aging symptoms, see the
Cross-Reference List of Anti-Aging Medicines
International Anti-Aging Systems
, and the
Life Extension Foundation
Also see the research programs to find and identify previously unknown
The Long-Range Impact & Reproduction
Our advanced programs for cyclic telomerase activation
and cellular therapy including cell membrane rejuvenation
elimination of cellular lipofuscin
DNA screening, mitochondrial biogenesis
Pyrroloquinoline Quinone (PQQ)
accelerated DNA repair
drugs will probably result in youthful patterns
of gene expression maintained for many decades, or even centuries, so that women will not go through menopause
until much later than they now do.
will probably experience
of their pre-menopausal state
as a consequence of using the above drugs and
medicines like fenugreek extract
or black cohosh
It is commonly believed that when oocytogenesis is completed,
no additional primary oocytes are created to make human ova,
so that oocytes reach their maximum at about 20 weeks of gestational age, when there are approximately
seven million of them.
Recently, this has been challenged by new observations
This should make it possible to maintain a pool of fertile men and women for any required substantial recovery
in a natural way as we approach physical immortality with rejuvenation included.
Our goal will be to maintain youthful cellular condition as fertile young adults,
a strategy which also provides the best protection against diseases of old age due to
In other words, we will work to minimize our population of
and we shall now proceed
to construct the immortal phenotype.
Accidents will continue to remove individuals from the population,
and the program of evolution of the human phenotype may be continued on a different time scale.
Evolution, our old ace in the hole for confronting difficulties requiring physical adaptation,
has been increasingly proceeding outside of our physical bodies as we have developed vehicular instrumentalities
instead of longer, faster limbs and books and computers with worldwide data networks instead of bigger,
It is no longer necessary to develop specializations for hunting in new terrestrial environments
now that special clothing, sunscreens, and sunglasses are available, so that physical evolution of the
mortal body is relatively outmoded.
Programmable machines and robots will become increasingly available
to perform most dangerous or potentially damaging work.
Chromosome-targeted and cell-targeted therapies will have evolution and its partner death
working on a much longer time-scale than heretofore.
O Death, where would we be without you?