Encapsulated link for interesting friends
Thursday, August 2, 2018
Wednesday, August 1, 2018
Biology of Aging for Engineer friends
https://www.youtube.com/watch?v=AIzEjm7O11M&feature=youtu.be
The purpose of these series of notes is not to convert into
new researchers, only to provide a basic set of ideas to understand some work. Entwined are descriptions
of some kingdoms, for some botany, entomology etc. are also needed and thrown
in. 99.99% human believe that aging is natural. I don't, and have reasons to believe in life extensions before expected death naturally and even widespread life extension in USA by end of 2020. Any life-extension would dwarf every political dispute ever.
Life is cellular. Less than a cell are viruses.
They are perfect salts and reproduce only by invading a host. Routinely, they attack
true unicellular beings called bacteria (or archea etc). This attack and
destruction can be utilized for narrow spectrum antibiotics against resistant
bacteria!
Most important to any life is a cell. A cell for us the main
DNA and 0 to 2000 mitochondria. 0 in red blood cells to 2000 in liver
cells. Mitochondria have their own DNA
and give rise to own diseases and aging However we ignore aging from it,
focusing on main DNA in the nucleus.
The study of aging -
gerontology - is a relatively new science that has made incredible progress
over the last 30 years. In the past, scientists looked for a single theory that
explained aging. There are two main groups of aging theories. The first group
states that aging is natural and programmed into the body, while the second
group of aging theories says that aging is a result of damage which is
accumulated over time. In the end, aging is a complex interaction of genetics,
chemistry, physiology, and behavior.
By understanding and describing how we age, researchers
have developed several different theories of aging. The two categories are
programmed theories and error theories.
- Programmed Theories assert
that the human body is designed to age and there is a certain biological
timeline that our bodies follow.
- Programmed
Longevity: Aging is caused by certain genes
switching on and off over time.
- Endocrine Theory: Changes
in hormones control aging.
- Immunological Theory: The
immune system is programmed to decline over time, leaving people more
susceptible to diseases.
- Error
Theories assert that aging is caused by environmental
damage to our body's systems, which accumulates over time.
- Wear and Tear: Cells
and tissues simply wear out.
- Rates of Living: The
faster an organism uses oxygen, the shorter it lives.
- Cross-Linking: Cross-linked
proteins accumulate and slow down body processes.
- Free Radicals: Free
radicals cause damage to cells that eventually impairs function.
- Somatic DNA Damage: Genetic mutations cause cells to
malfunction.
I have no toleration towards people who subscribe to
programmed theories, even if they were to be mostly right because if there is
any man-effort in challenging the gods, that belief weakens my morale!
Genetics and Aging
Studies have demonstrated that genetics can play a major
role in aging. When researchers adjust the genes in certain mice, yeast cells,
and other organisms, they can almost double the lifespan of these creatures.
The meaning of these experiments for people is not known, but researchers think
that genetics account for up to 35 percent of the variation in aging among
people. Some key concepts in genetics and aging include:
- Longevity Genes: There are specific genes which help
a person live longer.
- Cell Senescence: The
process by which cells deteriorate over time.
- Telomeres: Structures
on the end of DNA that eventually are depleted, resulting in cells ceasing
to replicate.
- Stem
Cells: These cells can become any type of cell in the
body and hold promise to repair damage caused by aging.
Biochemistry
No matter what genes you have inherited, your body is
continually undergoing complex biochemical reactions. Some of these reactions
cause damage and, ultimately, aging in the body. Studying these complex
reactions is helping researchers understand how the body changes as it ages. Important
concepts in the biochemistry of aging include:
- Free Radicals: Unstable oxygen molecules which can
damage cells.
- Protein
Cross-Linking: Excess sugars in the bloodstream can
cause protein molecules to literally stick together.
- DNA
Repair: For unknown reasons, the systems in the body
to repair DNA seem to become less effective in older people.
- Heat
Shock Proteins: These proteins help cells survive
stress and are present in fewer numbers in older people.
- Hormones: The
body's hormones change as we age, causing many shifts in organ systems and
other functions.
Body Systems
As we age, our body's organs and other systems make
changes. These changes alter our susceptibility to various diseases.
Researchers are just beginning to understand the processes that cause changes
over time in our body systems. Understanding these processes is important
because many of the effects of aging are first noticed in our body systems.
Here is a brief overview of how body systems age:
- Heart Aging: The
heart muscle thickens with age as a response to the thickening of the
arteries. This thicker heart has a lower maximum pumping rate.
- Immune
System Aging: T cells take longer to replenish in
older people and their ability to function declines.
- Arteries
and Aging: Arteries usually to stiffen with age,
making it more difficult for the heart to pump blood through them.
- Lung
Aging: The maximum capacity of the lungs may decrease
as much as 40 percent between ages 20 and 70.
- Brain
Aging: As the brain ages, some of the connections
between neurons seem to be reduced or less efficient. This is not yet well
understood.
- Kidney
Aging: The kidneys become less efficient at cleaning
waste from the body.
- Bladder Aging: The
total capacity of the bladder declines and tissues may atrophy, causing
incontinence.
- Body
Fat and Aging: Body fat increases until middle age
and then weight typically begins to decrease. The body fat also moves
deeper in the body as we age.
- Muscle
Aging: Muscle tone declines about 22 percent by age
70, though exercise can slow this decline.
- Bone
Aging: Starting at age 35, our bones begin to lose
density. Walking, running and resistance training can slow this process.
- Sight
and Aging: Starting in the 40s, difficulty seeing
close detail may begin.
- Hearing and Aging: As
people age, the ability to hear high frequencies declines.
Behavioral Factors
The good news is that many of these causes of aging can
be modified through your behaviors:
- By eating foods
loaded with antioxidants, you can minimize damage
caused by free radicals.
- By exercising,
you can limit bone and muscle loss.
- By keeping your cholesterol low, you can slow the
hardening of your arteries and protect your heart.
- By practicing mental
fitness, you can keep your brain sharp.
Lifestyle
factors have also been shown to extend life. Rats and mice on a
calorie restricted diet (30 percent fewer daily calories) live up to 40 percent
longer. Positive thinking has
also been shown to extend life in people by up to 7.5 years.
Cell Biology
Components of a typical animal cell:
12. Lysosome
Remember that a cell does ALL the things that a life does,
all without any magic, spirituality etc, by simple chemistry in my thinking. It
is simple if known, very hard if not. Energy is produced by Krebs cycle from
food particles, which are carbohydrate, protein or fat through Krebs cycle.
This very complicated cycle is idealized as three sub cycles with one tracer
molecule. The three tracers are NAD+, ATP and rest of citric acid cycle. NAD
which in turn can be synthesized or reused by salvage cycle from the waste
products of the previous sub cycle. Synthesis from amino acids is rare. Salvage
step is constructed from NMN. NR makes
NMN with the NAMPT filter. Best idealization in my mind is that NMN is one step
away while NR is two steps away from NAD+ we need. Direct NAD+ is a bad idea. Every
step in biology is about 10% from bio-availability. NAD+ is produced inside
mitochondria.
Bioavailability is great engineering block on all bioscience!
Consider CoQ10 which is required by the ATP sub cycle. There
are commercial losses before eating. Then there are stomach wall losses, while
the molecule enters the blood stream. Then there are cell absorption losses.
Finally there are losses to mitochondrial wall. There is always the limiting
concentration of the safe carriage of the chemical in blood. So you can at most
ingest 1000 mg of CoQ10 is the safe limit on ingesting. Lucky to get 10 mg on
all mitochondria!
Science is about determining effects, doctors are really
engineers that determine what is needed, then package the needs based on
quantity, time and dosage considering the side effects.
Bioavailability is crucial.
It is. So low for glutathione anti-oxidant and melanin
reducer (skin whitens). So much that useless in quaff form. Best injected into
bloodstream by a drip. That means a medical establishment, common in Korea and
opening in India slowly. In both cultures, fairness of skin enhances marriage
value! Another is resveratrol.
It is the latest failure – great bioscience but poor engineering with
catastrophic unpassable bio-availability failures.
What is Coq10?
It is a vitamin like substance which acts as a usefulanti-oxidant in ATP production and thus helps the heart muscle with
mitochondria-rich cells. I recommend it at 400 mg per day in divided doses to
all above 60, independent of need, solely for Aging disease.
What is called (Arun neologism) a wittig form?
By witting
reaction, a form of CoQ10 exists without losses in mitochondrial absorption.
Not surpsingly, this form called Mitoq needs only 5mg to equal 500 mg of CoQ10!
The general concept is conversion of any molecule to a form that delivers the
base molecule without losses at mitochondria.
What more about wittig forms?
There are no wittig forms that came from literature
searches except one, the skq1 molecule
similar to Mitoq, is loved by Russians and being human tested for anti-aging
properties. The wiitigified anti-oxidant is however plant based. Mitoq I
suspect has Anti-aging
properties not tested properly because it is very pricy ($1-2 per day) (link
discounted as sales-pitch). SKQ1
has been approved for human use in Russia! Sold in drug stores!
In many ways 2018 is a water-shed year between classic
think and new quantum-think. The old dreams will cease to realistic, new
dreams will be radically different. I envy those being born. It is all about
exponential speed up. An Arab fighter of 1000AD would not have much to learn in
1500 in launch of ships to America. The world changed radically between 1500
and 2000. That difference now happens in 20 years! About others I don’t know,
but I still remember CS MTech (1975-1977) at IIT Kanpur and me trying to guess
what humans would do with projected IBM mainframe on a chip! There was no
internet, Microsoft, Google or Apple or Facebook or mobile phens then! Even more shocking is
about encryption in 2000 and today! In 2000AD, I saved for a Gigabyte drive and
128K memory. My latest purchase is 8 GB RAM and 4 TB disks
.
Past the watershed is my phone-sleeve (surrounds any phone for) universal panic button, reminder's to eat medicine - programmable sleeve not software, mobiles that can do lot more using local AI, 5G and killing of TV. Welcome to the 2nd industrial revolution, WHERE DEATH IS RARE AND 1ST GENETIC REVOLUTION WHERE DEBILITATION IS RARE..
Stem cells
Past the watershed is my phone-sleeve (surrounds any phone for) universal panic button, reminder's to eat medicine - programmable sleeve not software, mobiles that can do lot more using local AI, 5G and killing of TV. Welcome to the 2nd industrial revolution, WHERE DEATH IS RARE AND 1ST GENETIC REVOLUTION WHERE DEBILITATION IS RARE..
Stem cells
A human is formed from union of male and female pluripotent cell repatedly splitting and specializing. Apoptosis message are generated to delete cells produced, The entire process is probabilistic. Biologists classify cells whicch are not in their final specialization into pluripotent 9all can form) to multipotent Mesenchymal stem cells or MSC. Most early researchers used human PSC obtained from abortions. Nowadays iPS cells (induced) exist which are artificially created.
Mesenchymal stem cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes(cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue).
So called iPS are created many ways - one is small chemical/biological modifications of extracted bone marrow from the patient. These can be coaxed into dopamin bearing cells for humans!
Tuesday, July 31, 2018
Idea of Arun Arya trial, better than FDA now
There are 4 phases to a trial accepted by FDA
·
Phase I determines if
a treatment is safe in humans (this is conducted in an ‘open label’ manner)
·
Phase II ‘double
blindly’ assesses in a small cohort of subjects if the treatment is effective
·
Phase III involves
randomly and blindly testing the treatment in a very large cohort of patients
·
Phase IV (often
called Post Marketing Surveillance Trials) are studies conducted after the
treatment has been approved for clinical use
In open label, the researchers and patients are known to
each other and investigator. It is Phase II/III which is actively sabotaged by
true patients since many are unhappy at secretly be chosen as guinea-pigs fed
the ineffective placebo.
The Arya trial keeps the other phases intact, only modifies
Phase II/III . Squeamishness of real patients is considered genuine and undermining
of Phase II/III considered rational. A MUCH better approach is not to compare
against ineffective but another best treatment at this time. Point is then
there is no rational strategy and what you get is how much better this
treatment is, over the past.
Only in rare cases a placebo be used. Only in cases of new vaccines
does one truly need a placebo. Even in this case, one can subject one half to placebo
and other to placebo then, and assume that trial was twice as big, and of half
the duration!
Monday, July 30, 2018
The Science of Parkinson – Arun’s view on Aging 3
I study Parkinson because it will strike. Unlike most more,
it is NOT the headache of the doctor for best care. Anyone who plans to live
post 90 will be hit by Alzheimer, Parkinson or essential tremor, I am just
grateful to USA for early diagnosis. Happens to dovetail into fight against
Aging. I have no intention of living even 150 afflicted with these elderly
diseases.
This
is excellent reference for keeping track of new researches. It is a
periodical, good enough to serve honest historical documentation of the field.
Great source 0f quotations. Past quickly shows what excited the field, NAD is
just 1 of many in the sequence of LRRK2, EEF2 inhibitors etc. So wat is new and Game
changing about NAD other than I picked it!
One thing that even if I am totally wrong, the efforts will
have positive effects in an even deadlier disease, namely aging! A second
reason is the absence of some miraculous chemistry that underlies Parkinson.
Science is very mysterious but only till it is understood! Broad-spectrum
strategies exist to convert science into engineering. I have become quite
proficient in dentistry by always asking my sir Dentist interesting questions.
Fortunately, he is a professor of dentistry in local college too. That is why I
am confident that I will be the first human to lick Parkinson. Way I look at
it, it is not worse than TBI and I have a running start. Another is my devotion
to contemporaneous (Bell labs, Murray hill) best example of beautiful mind,
alas no more, defeating his likely TBI. If I can think of having licked TBI,
what is Parkinson and likely Dementia
that follows? Note that it is the major reason for state of mind before death
of most elderly!
So the trick is to pursue NAD. NMN will help, as with NR,
although FDA is out of NR v. NMN fight. Best yet is that Nicotinamide crosses
that blood-brain barrier too!
Crossovers (like Aging and Parkinson) never cease to amaze
me. Consider “Graphene quantum dots prevent α synucleinopathy
in Parkinson’s disease”! Next I
expect “Quantum theory applications in management of Parkinson” !
Theories of Aging - ARUN's VIEW 2
The stupidest theory believed by 99% of humans is on Aging
is “that is how God or Nature wills it”. Aging is a disease, FDA disagrees,
their reason is that “no one has established provable (empirically visible)
improvements of the purported disease”. It leaves the field open to likes of Dr.
Gurante, enormously gifted faculty from MIT who was a faculty advisor to Dr.
Sinclair and Dr. Matt Kaeberlein at M
IT, has assembled a team of Nobel Laureates at Elysium, and
peddles an excellent but very mild improvement in aging, if at all, in my
opinion. They CAN avoid FDA since supplements are not drugs and they are
careful to avoid FTC! The war between NR and NMN has no federal referee!
Situation is Similar in India except that FSSAI seems to some control over mix of drugs like Vitamin and supplement claims.
Situation is Similar in India except that FSSAI seems to some control over mix of drugs like Vitamin and supplement claims.
My theory of aging is
proven to me by the observation that all cell based life ages and that cells
have have Hayflick limit of about 50 subdivisions before apoptosis. In fact I
consider the HL essential to life because the only cells with unlimited life
are cancer cells, avoided only by apoptosis! This is why I do not consider nmn
to be a final fix, just enough to extend the age to 150, longer life happening
by transfection, which allows some trees to live few thousand years even with
the HL since every cell division has a stem cell dividing too, and the stronger
cell survives. Telomere is a red herring!
Given my belief, have narrowed down to a
regimen, expect to be able to do it within a few months, see no urgency in
applying it. I expect world to be so by 2020. In fact, there is NO probability
advantage in following any particular life style. I expect (weak claims even now) of
improvements in heart disease and Alzheimer’s from nmn. There is nothing urgent
for self.
But wait. There are two reasons for speed. One I
visited USA and underwent 3 MRI and one MRA, why irrelevant. What was discovered was the start
of Parkinson. Confirmed on return to India. Poor doc here had no way to decode
the CD I got. Never mind, I will make 4 color prints next time. Nothing better
than excise and L-DOPA till the latter misses effectiveness due to progressive
doping. But there is a blog that analyses NR in Parkinson! To cut the long short, NAD boost helps PD! That is because NR can cross blood-brain barrier and salvage NAD+ helps with neuro-protective effects. NR has been tested to 1000 mg per kilo, so is human safe. It does show promise as it is effective against neurotoxins. This is common property of all forms of vitamin B3, including Niacin. Given the cost-differential I have started on Nicotinamide, non-flushing Niacin,- just overdose of water-soluble vitamin i.e. useless in worst case. Of course, NMN is planned, is better than NR, provided it can bypass brain barrier. It can very well following a vigilant search!
Two, it is not so for Dad. He, rightly, will not listen to my theories. His doctor’s do not oppose but say only that they expect no benefit or find human trial empirical evidence on internet (there is anecdotal and mouse based). So I will begin soon on self, hopefully this self-test will either cure me of pretensions of philosophical/chemistry aggregation of dependable researches, or push him into doing it. MY full regimen is significant exercise + metformin + nmn + Mitoq. I expect significant exercise + metformin + nmn + coQ10
Two, it is not so for Dad. He, rightly, will not listen to my theories. His doctor’s do not oppose but say only that they expect no benefit or find human trial empirical evidence on internet (there is anecdotal and mouse based). So I will begin soon on self, hopefully this self-test will either cure me of pretensions of philosophical/chemistry aggregation of dependable researches, or push him into doing it. MY full regimen is significant exercise + metformin + nmn + Mitoq. I expect significant exercise + metformin + nmn + coQ10
within a month, anecdotal self-proof within 4
months and business plan for metformin +
nmn + Mitoq within 7 month (in 4 sublingual pill supplement per day). Only
diversion is self-pursuit of ECP and HOT first, by then!
By then my doors will be ready for in-house 2
month plans for ECP (To date, more than 300 studies have been published showing the benefits of ECP therapy) and Hyperbaric-oxygen-therapy (HOT) (Popuaar with aged Movie stars but also bad wounds, sports, TBI etc) along with
supplementation! I do no drugs, hence immune to IMA and only claim improvements
to Aging, not a disease even in India! If positive effects are reached by
willing friends and relatives first few years, that is good enough. If all
works according to plan, I have captive facility of High-quality life-extension for family for repeats every
3-5 years for life for under a crore!
What is cell transplantation?
Parkinson’s is a progressive neurodegenerative condition.
This means that cells in the brain are slowly being lost over time.
What makes Parkinson’s particularly interesting is that certain types of brain cells are more affected than others. The classic example of this is the dopamine neurons in an area of the brain called the substantia nigra, which resides in the midbrain.
![d1ea3d21c36935b85043b3b53f2edb1f87ab7fa6](https://scienceofpd.files.wordpress.com/2017/05/d1ea3d21c36935b85043b3b53f2edb1f87ab7fa6.jpg?w=830)
The number of dark pigmented dopamine cells in the substantia nigra are reduced in the Parkinson’s brain (right). Source: Adapted from Memorangapp
Approximately 50% of the dopamine neurons in the midbrain (not me with very early analysis) have been lost by the time a person is diagnosed with Parkinson’s (note the lack of dark colouration in the substantia nigra of the Parkinsonian brain in the image above), and as the condition progresses the motor features – associated with the loss of dopamine neurons – gradually get worse. This is why dopamine replacement treatments (like L-dopa) are used for controlling the motor symptoms of Parkinson’s.
Friday, July 27, 2018
AGING RESEARCH – ARUN’S VIEW 1
Self link
These are notes to self, made available in hope they will attract tough comments, reveal my directions and their reason; are not intended to hurt any views – I am a stoic, perhaps buddhist, consider all not so to be noxious vermin, but see no reason to propagate my views. Some people who can discern scholastic approach to questions (hard stoic but not skeptic) requiring a rational conclusion for all questions rangfing over UNinteresting to besides the point to sophistry if unrational, Rational stoic (not a persistent skeptic!) to distance from pure scientist.
These are notes to self, made available in hope they will attract tough comments, reveal my directions and their reason; are not intended to hurt any views – I am a stoic, perhaps buddhist, consider all not so to be noxious vermin, but see no reason to propagate my views. Some people who can discern scholastic approach to questions (hard stoic but not skeptic) requiring a rational conclusion for all questions rangfing over UNinteresting to besides the point to sophistry if unrational, Rational stoic (not a persistent skeptic!) to distance from pure scientist.
the fellows
referenced have a common theme
approach is
scientific path to amortality
consider empirical
studies on humans to be gold standard
are in possesion
of data on models
have narratives on
why applicable to humans
experiment on self
first
have reasons to
believbe they are honest
are not
commercially driven (OK after studies only)
hence can be
emulated pre-proof
FORGET
THE BLOOD OF TEENS. THIS PILL PROMISES TO EXTEND LIFE FOR A NICKEL POP.
Dr. Nir
Barzilai is the director of the Institute for Aging Research at the Albert
Einstein College of Medicine and the Director of the Paul F. Glenn Center for
the Biology of Human Aging Research and of the National Institutes of Health’s
(NIH) Nathan Shock Centers of Excellence in the Basic Biology of Aging. He is
the Ingeborg and Ira Leon Rennert Chair of Aging Research, professor in the
Departments of Medicine and Genetics, and member of the Diabetes Research
Center and of the Divisions of Endocrinology & Diabetes and Geriatrics.
Dr.
Barzilai’s research interests are in the biology and genetics of aging. One
focuses on the genetic of exceptional longevity, where we hypothesize and
demonstrated that centenarians have protective genes, which allows the delay of
aging or for the protection against age-related diseases. In a Program he is
leading we take full advantage of phenotypes, DNA, and cells from the Ashkenazi
Jewish families with exceptional longevity and the appropriate controls and his
group have established at Einstein (over 2600 samples of which ~670 are
centenarians) and discovered underling genomic differences associated with
longevity. Longevity Genes Project (LGP) is a cross-sectional, on-going
collection of blood and phenotype from families with centenarian proband.
LonGenity is a longitudinal study of 1400 subjects, half offspring of parents
with exceptional longevity, validating and following their aging in
relationship to their genome. The second direction, for which Dr. Barzilai is
holding an NIH Merit award that focuses on the metabolic decline of aging, and
his team hypothesize that the brain leads this decline. His lab has identified
several central pathways that specifically alter body fat distribution and
insulin action and secretion by intraventricular or hypothalamic administration
of several peptides that are modulated by aging including: Leptin, IGF-1,
IGFBP3 and resveratrol.
He has
received numerous grants, among them ones from the National Institute on Aging
(NIA), American Federation for Aging Research, the Ellison Medical Foundation
and The Glenn Medical foundation. He has published over 230 peer-reviewed
papers, reviews, and textbook chapters. He is an advisor to the NIH on several
projects and serves on several editorial boards and is a reviewer for numerous
other journals. Dr. Barzilai is in the board of the American Federation for
Aging Research, is its co-scientific director, and has served on several NIA
study section. He is also a founder of CohBar Inc., a biotech that develops
mitochondrial derived peptides as therapy for aging and its diseases. He is
co-PI on the R24 Geroscience (Apollo) grant that is an effort to move the field
of aging to translation. Dr. Barzilai has been the recipient of numerous
prestigious awards, including the Beeson Fellow for Aging Research, the Ellison
Medical Foundation Senior Scholar in Aging Award, the Paul F. Glenn Foundation
Award, the NIA Nathan Shock Award, and the 2010 Irving S. Wright Award of
Distinction in Aging Research.
He is
currently leading an international effort to approve drugs that can target
aging. Targeting Aging with METformin (TAME) is a specific study designed to
prove the concept that multi-morbidities of aging can be delayed by metformin,
working with the FDA to approve this approach which will serve as a template for
future efforts to delay aging and its diseases in humans.
Born in
Israel, Dr. Barzilai served as chief medic and physician in the Israel Defense
Forces. He graduated from The Ruth and Bruce Rappaport Faculty of Medicine at
the Technion-Israel Institute of Technology in Haifa and completed his
residency in internal medicine at Hadassah Medical Center in Jerusalem. He
served in a refugee camp during the war in Cambodia (1979-1980) and built a
nutritional village in the homeland of the Zulu (1983 – Kwazulu). He has
completed 2 fellowships at Yale (metabolism) and Corenell (Endocrinoology and
molecular Medicine). He was an invited speaker to the 4th Israeli President
Conference (2012) and a Vatican conference on efforts to enhance cures (2013,
2016). He has also taken part in Global initiatives and spoke at The Milken
Global Institute, Asian Megatrends and is an advisor for the Prime Minister of
Singapore on Aging. Dr. Barzilai has been on the ‘Forward 50, top 50 influence
Jews in the US (2011). His work has been profiled by major outlets, including
the New York Times, the BBC and PBS' NOVA science now, TEDx talk Science and is
the leading feature on the Ron Howard/Jonathan Silberberg/National Geographic
film about the Age of Aging.
Matt Kaeberlein (born 1971[1]) is an American biologist
and biogerontologist best
known for his research on evolutionarily conserved mechanisms of aging. He is
currently a Professor of Pathology at the University of Washington in
Seattle.
James Kirkland, and
The major research focus
of James L. Kirkland, M.D., Ph.D., is the impact of cellular aging (senescence)
on age-related dysfunction and chronic diseases, especially developing methods
for removing these cells and alleviating their effects. Senescent cells
accumulate with aging and in such diseases as dementias, atherosclerosis,
cancers, diabetes and arthritis.
The goal of Dr.
Kirkland's current work is to develop methods to remove these cells to delay,
prevent, alleviate or partially reverse age-related chronic diseases as a group
and extend health span, the period of life free of disability, pain, dependence
and chronic disease.
Focus areas
·
Cellular senescence. Dr. Kirkland's team developed the
idea that removing senescent cells may enhance health span, partly based on the
observation that mice with mutations that increase life span have lower senescent
cell burden than normal mice, and that short-lived mice have more of these
cells. To test this idea, Dr. Kirkland and his team, in collaboration with
others at Mayo Clinic, eliminated senescent cells from genetically modified
mice, in which a drug-activated "suicide" gene was expressed only in
senescent cells. They found that this process enhanced health span, at least in
the context of an accelerated aging-like disease. This gave proof of principle
for the notion that clearing senescent cells with a drug in
non-genetically-modified individuals might be beneficial. They continue to work
on developing interventions that selectively target senescent cells.
·
Diabetes, other chronic diseases and cellular senescence. Diabetes and
obesity are associated with accumulation of senescent cells in fat and other
tissues. Dr. Kirkland's group is working on ways to reduce severity and
alleviate the complications of diabetes by clearing senescent cells or blocking
them from producing factors that cause or exacerbate dysfunction. Effects of
eliminating senescent cells or the factors they release are being investigated
on frailty and a range of other chronic disorders in Dr. Kirkland's laboratory
and with collaborators at Mayo and other institutions.
Significance to patient care
Dr. Kirkland's work is
important in developing methods to enhance health span and delay onset of the
chronic age-related diseases as a group, rather than one at a time. These
conditions, including diabetes, dementias, atherosclerosis, cancers and arthritis,
among others, account for the bulk of morbidity, mortality and health costs in
most of the world.
he Sinclair Lab studies
the processes that drive aging and age-related diseases, and works toward
discovering methods for slowing down or reversing these processes. Work ranges
from dissecting novel pathways and identifying target genes, to assessing small
molecules that may slow the pace of aging and increase healthspan. The overarching
goal is to establish new biological approaches that can be translated into
radically different medicines to promote longer, more productive lives. A focus
is on how genetic and epigenetic changes drive aging, common diseases and
disorders such as cancer, heart disease, inflammation, neurodegeneration,
infertility and diabetes. To advance our studies we use a wide range of
genetic, genomic and proteomic tools. In addition we employ several unique
mouse models to assess the role of these factors and how well genetic and
pharmacological agents may impact them. We are a team with a broad range of
skill sets, who work together and complement each other to solve key scientific
questions about mammalian biology and human health. Skills in the lab range from
enzymology and biochemistry, to genetics, genomics, proteomics and systems
biology.
Their recommendations
compress to two – metformin and NMN. I add a third - MITOQ. Here is my
reasoning – pointless to debate but med MD-PhD. ALL life is cellular, all animals
age. So aging is cellular – mitochondria based. MITOQ feeds COQ10 to Mitochondria
bypassing all, to be greatly bio-available. No wittig-like Carrier for NMN or
metformin. Metformin good for actual diabetic and aging pseudo-diabetics. Insulin
promotes aging as do high sugars! Sublingual administration of 500 mg of NMN
per day is twice the dose taken by Sinclair! Metformin is dirt cheap. MITOQ is
$1 per day, so is NMN. That plus NMN and exercise is to be given up, if no
benefits in 3 month. The drugs should enable you to do exercise! If you
attribute your health to exercise, don’t forget what enabled you!
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