Blog 66 LIVE LONGER VIA REVERSE AGING TECHNOLOGIES BY AWARD-WINNING AUTHOR, ADVENTURER, AND SCIENTIST MARK KINGSTON LEVIN PhD
David Sinclair, Ph.D. reported reversing aging in mice. Scientists claim to be a step closer to reversing the aging process after rejuvenating worn out organs in elderly mice. The experimental treatment developed by researchers at the Dana-Farber Cancer Institute, Harvard Medical School, turned weak and feeble old mice into healthy animals by regenerating their aged bodies.
Figure 1, David Sinclair and team at University of New South Wales near Sydney Australia. Dr. Sinclair, also at Harvard Medical School, reversed aging in mice. Credit University of South Wales Australia (UNSW).
“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said lead author Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School in Boston, MA USA.
Let’s take a look at how we got here and where we will go to extend longevity in humans.
In 1934, findings that calorie restriction can extend lifespan by 50% in rats started the anti-aging craze. The existence of species having negligible senescence (the condition or process of deterioration with age) and potential immortality, such as hydra, has motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases. More recently at Harvard, David Sinclair reversed aging in Mice and is now testing on humans, an Earth-shaking discovery in biology.
- What is the preferred area of aging research that is most promising? There are many approaches, yet the simplest may be NAD+ as an anti-aging pill because it has reversed aging in mice.
- Another method is removing damaged cells. Some cells die, and the body is sometimes poisoned by senescent cells. These cells cannot divide but are still able to produce chemical signals or poisons. Many scientists think these cells could be important in heathy aging, which means treatment could play a role in the battle against aging.
“It is thought that these cells and the substances they produce are involved in the process of aging,” longevity researcher Nicolas Musi from the University of Texas at Austin told MIT Technology Review. “The idea is that removing these cells may be beneficial to promote healthy aging and also to prevent diseases of aging.”
Early studies indicate there may be something to that hypothesis.
- Dr. Musi and his colleagues published the results of an early trial in which they treated 14 patients suffering from the fatal lung condition idiopathic pulmonary fibrosis (IPF) with a drug combination they believed would clear out senescent cells.
The patients took nine doses of a leukemia drug called dasatinib and quercetin, a supplement, for three weeks. By the end of the trial, the patients were reportedly able to walk farther than they could previously in the same amount of time alongside other signs of improved wellbeing. They did not report any serious side effects.
“Though small, this pilot study marks a breakthrough in how we treat age-related diseases such as IPF,” researcher Jamie Justice said in a press release. “Here, we’ve therapeutically targeted a fundamental biological hallmark of aging that is implicated in IPF, and we show early but promising results for the first time in human patients.”
Right now, it’s hard to say whether the drug combo would actually prove effective as an anti-aging therapy, but the researchers are committed to finding out. They’re already testing the treatment on a group of 15 more lung patients, as well as 20 people suffering from chronic kidney disease.
“If we see effectiveness signals and don’t encounter really bad side effects, we’ll try to get to people with less and less life-threatening conditions,” researcher James Kirkland told MIT Technology Review. “If everything goes right.”
- Many people are selling exercise coaching, diet and vitamins. Skin cream is a multi-billion-dollar business. Hormone therapy for men and women is growing every year, methods to increase male and female hormones such as estrogen and testosterone that keep people feeling and acting young and vital.
- Breakthrough: Scientists reverse aging in human cells
Ana Sandoiu of Medical News Today reported on Wednesday 8 November 2017 about new research published in the journal BMC Cell Biology showing that old human cells can be rejuvenated using simple chemicals similar to resveratrol, a substance found in red wine and dark chocolate.
Seniors may soon be able to live disease-free for their entire lives.
The new study was carried out by researchers at the Universities of Exeter and Brighton, both of which are located in the United Kingdom. Professor Lorna Harries conducts molecular genetics research at the University of Exeter. The first author on the paper is Dr. Eva Latorre, a research associate at Exeter.
- Scientists at Tsukuba University in Japan reported very promising results on reversing aging; the modern Fountain of Youth. They reported that human aging may be able to be reversed at a basic level of human cell lines. In the process, the researcher also found that regulation of two genes is related to how we age.
The new results overturn a former popular theory of aging that fixes the blame for humans’ inevitable downhill slide on mutations that accumulate in our mitochondrial DNA over time. “Mitochondrion are sometimes likened to a cellular ‘furnace’ that produces energy through cellular respiration. Damage to the mitochondrial DNA results in changes or mutations in the DNA sequence that build up and are associated with familiar signs of aging like hair loss, osteoporosis and, of course, reduced lifespan.”
Figure 3 Tsukuba scientist Jun-Ichi Hayashi suggest that their research indicates that one amino acid is used for switching on and off genes. The team led by Professor Jun-Ichi Hayashi was able to flip the switches on a few genes back to their youthful position, effectively reversing the aging process!!
“The researchers came to this conclusion by comparing the function level of the mitochondria in fibroblast cell lines from children under the age of 12 years to elderly people between 80 and 97. As expected, the older cells had reduced cellular respiration, but the older cells did not show more DNA damage than those from children.” These astonishing results are a key modern Fountain of Youth. The Japanese team proposes that the reduced cellular function is tied to epigenetic regulation. We all can now change or turn on or off the DNA without affecting the DNA sequence itself. “Epigenetic changes could possibly be reversed by genetically reprogramming cells to an embryonic stem cell-like state, effectively turning back the clock on aging.” This is wonderful news for people over 12 years old.
To test the theory, the researchers found two genes associated with mitochondrial function and essentially experimented with turning them on or off. In doing so, they were able to create defects or restore cellular respiration. These two genes regulate production of the amino acid glycine in mitochondria, and in one of the more promising findings, a 97-year-old cell line saw its cellular respiration restored after the addition of glycine for 10 days.
The Japanese scientists’ research paper was published in May 2015; please see the journal Scientific Reports.
- 7. Similar research performed at the Salk Institute in La Jolla, CA has also recently looked at other ways to slow down or stop aging at a cellular level.
- Another group is investigating a new class of drugs called senolytics that could help slow aging.
Sandoiu reports that the new study builds on previous research from the University of Exeter that found that so-called splicing factor proteins tend to become inactive as we age.
Researchers added chemicals like resveratrol to aging human cells and found they reactivated these splicing factors. Thus, not only made the old cells appear younger, but started dividing again, as expected.
“When I saw some of the cells in the culture dish rejuvenating I couldn’t believe it,” says Dr. Latorre in Sandoiu’s report. “These old cells were looking like young cells. It was like magic.”
“I repeated the experiments several times and, in each case, the cells rejuvenated. I am very excited by the implications and potential for this research,” Dr. Latorre adds.
Resveratrol is a compound found in peanuts, grapes, red wine, dark chocolate, and some berries.
- One Key to Anti-Aging
According to Dr. David Woynarowski, MD, CPT: “Telomeres are the last part of your genetic material. They are often referred to as the Biologic Time Clocks because of their huge influence on life span. When those telomeres shorten, it has a negative effect on your health and longevity.
“Studies using telomere elongation in animals have shown an extension in life span and produced remarkable health benefits. Because of fear of government intervention, the only studies done in humans have been in those infected with chronic viruses like HIV and CMV. In those studies, telomere length was restored, and the virus were cleared from their systems. Studies in humans looking at aging biomarkers also showed improvements!
“More and more scientists are understanding and pointing to the telomere as a major key to human health and longevity. Now, there is something simple and inexpensive you can do to take advantage of those findings!
“Other Benefits May Include:
“Receive daily antioxidants that help your body break down food and unhealthy chemicals. Help to support and activate the Immune System Defenses
“Better health and less impact from several diseases of aging including heart disease and Alzheimer’s disease.
“If you are not taking a telomere support supplement, then you are not doing everything you can to fight the aging process! If you are ready to have a fighting chance against Father Time, then harness the power of Mother Nature.”
Treatments can be recommended by your physician. I will not go into details about all the supplements and drugs you can take that should be recommended by your physician because every person is different and your physician knows your history.
“UCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.” Please see Science Daily from last fall.
Josh Mitteldorf of Aging Matters blog shares the following research innovations:
- AMP Kinase is a key chemical workhouse for energy production and regulation. In this study, the AMPK gene in fruit flies was found to be a signal that controls autophagy throughout the body. (Background: Autophagy is recycling at the cellular level. It declines through the lifespan, with the result that molecular gunk accumulates and production of properly-formed proteins declines.)
Life span and health span of the flies were increased when the gene for AMPK was activated in the nervous system, and independently in the digestive system.
Mitochondrial Damage vs Epigenetics
Jun-ichi Hayashi of Tsukuba University was an early enthusiast of the mitochondrial free radical theory of aging, who became convinced by his own lab results that the theory doesn’t work.
Background: Mitochondria are thousands of organelles inside a cell that burn sugar for electrochemical energy that the cell can use. They have their own DNA and their own reproductive cycles within a cell. They generate reactive oxygen species (ROS) as a byproduct, and it was an attractive theory to attribute aging to damage and mutations they suffer because they are at ground zero for high concentrations of ROS.
- Over the last two decades, we have learned that mitochondria do indeed play a central role in aging, but the story is not about simple damage. In his latest paper research article, see Science Daily, researchers from Hayashi’s lab show that there is no difference in the amount of DNA damage in mitochondria from cells of young people and from old people. Why then do mitochondria perform less well, and provide less energy in older people? They go on to propose that it is the epigenetic programming (in the cell nucleus, not the mitochondria) that makes the difference, and they identified two genes (GCAT and SHMT2) that may be all that is needed to restore youthful function to the mitochondria. These genes control production of glycine, the simplest of the 20 amino acids that are common protein constitutents. Simply feeding the cells with glycine also improved mitochondrial function. (You can buy glycine tablets as a supplement, but the body already has a lot, so it’s a good guess you would need a lot of it to make a difference. Food sources rich in glycine include gelatin, shrimp, spirulina, and raw ostrich meat.)
- Johnathan Labbadia at Northwestern University has discovered an epigenetic switch, a set of genes that is turned on that begins the aging process in lab worms [Research article from the Morimoto lab, Science Daily summary]. Worms begin aging at the tender age of 3 days, just a few hours after adulthood, with a switch that represses Heat Shock Protein. HSP is not just for heat, but a high-level signal that invokes a set of responses that create resiliency in response to stress of many kinds. In worms and in other animals, stress resistance is closely associated with longevity, and HSP is associated with longer life span in worms
Scientists who see aging as a purposeful, programmed event, myself included, look to mechanisms of epigenetic control, as we are hopeful that signaling can be modified to avert aging. But traditional evolutionary biology denies that there can be such direct control of aging. According to theory, such switches could only be flipped if flipping them increased reproduction in a way that more than offsets the loss of reproductive opportunity from aging. In keeping with the standard theories, Labbadia and Morimoto, looked for a connection to reproduction in the epigenetic switch they discovered. They found one, but–undermining the theory–they found that the benefits for reproduction and the costs in the form of aging could be easily separated.
13.”In one experiment, the researchers blocked the germline from sending the signal to turn off cellular quality control. They found the somatic tissues remained robust and stress resistant in the adult animals.”
Why doesn’t the worm do this, and get the best of both? Must be some kind of mistake, the Northwestern team asserts. “Dysregulation” has become a favorite word, though many have enough integrity and insight to be scratching their heads, wondering why there should be so much “dysregulation” involved in aging, when we rarely find anything else about the metabolism that is consistently dysregulated.
- This press release from University of Missouri describes evidence that cells of the arterial lining (epithelium) are more resistant to oxidative damage when they are older. Research from the lab of Steven Segal used hydrogen peroxide (H2O2) as a stressor. Peroxide is also known to be a multi-purpose signal molecule that can induce cell suicide (apotosis) in high concentrations, and can induce protective anti-aging response at lower levels.
The article is framed within an old and discredited view of that regards aging as a simple result of oxidative damage.
“Although the causes of many age-related diseases remain unknown, oxidative stress is thought to be the main culprit. Oxidative stress has been linked to cardiovascular and neurodegenerative diseases including diabetes, hypertension and age-related cancers.”
It should no longer surprise us that anti-oxidants are not anti-aging, or that pro-oxidants can be anti-aging, or that aging an active process controlled by central signals, not a passive process of damage.
Figure 4. Getting to the Bottom of Aging
- “This article claims to find the root of aging at the cellular level. It is in the endoplastic reticulum [background in a Kahn video]. The ER is a transport network inside the cell that directs each protein molecule to a targeted location. It does more than this–it finishes and folds the protein after it is manufactured. The new study finds differences between the ER of old and young cells, studied in lab worms and in cultured human cells. [Here is a Science Daily summary.] Proteins tend to be misformed and misfolded by the ER of old cells.
“In direct contrast to the article just above on blood vessels (“oxidative stress is thought to be the main culprit”), the claim here is that there is not enough oxidation in the ER of old cells. It is the reduced state of the ER that is responsible for misfolding of proteins.” This may help us understand Alzheimer’s and Parkinson’s diseases in the near future.
- Diverging Paths from Parabiosis Experiments: GDF11 and TGF-β. Amy Wagers is at the Harvard Stem Cell Center, where her biggest trophy so far is the discovery that GDF11 has rejuvenating effects in muscle and nerve cells. The implication is that there is not enough GDF11 in the blood in the blood of older mammals, and this is a source of aging.
In the early 2000s, Irina Conboy and Amy Wagers were grad students in Tom Rando’s Stanford University lab, studying parabiosis in mice. They learned that tissues in an old mouse could be rejuvenated by exchanging blood plasma with a young mouse.
Blood plasma is the liquid, containing dissolved signal molecules but no whole blood cells, no stem cells. The implication was that the old tissues could receive instructions from other parts of the body (an epigenetic clock?) causing them to get older or to revert to a younger state.
Irina and her husband Mike Conboy have a lab at UC Berkeley; they are focusing on TGF-β as one of the signals that causes aging. They are experimenting with a drug that blocks TGF-β receptor, and found that it has rejuvenating effects both on muscle and brain cells [research article].
The test results on GDF11 shows it is a form of TGF-β. The findings of Wagers and Conboy have diverged so dramatically that they are now opposite, which means I cannot believe anything.
David Glass claims he has been unable to duplicate Wagers’s work, and that in his experiments with mice, GDF11 seems to decline with age.
“GDF11 is a myostatin-homologous protein that acts as an inhibitor of nerve tissue growth. GDF11 has been shown to suppress neurogenesis through a pathway like that of myostatin.” Myostatin is an inhibitor of muscle growth with a structure that is 90% homologous to GDF11. This is a controversy that must be explained before we can take these compounds.”
- Keeping your Brain Active with Balance Exercises.
“A new study by Ross and Tracy Alloway of University of North Florida suggests that balance exercises improve working memory and protect against neurodegenerative disease.” [UNF press release]. I would not taking anything without seeing the details. The term “proprioception,” meaning awareness of body position, seems to be important but was not proven to me, Mark Kingston Levin PhD. “We all lose brain cells with age, and I think of Alzheimer’s dementia as one end of a spectrum.” Some herbs have been studied for neuroprotective effects. Vigorous exercise is neuroprotective, but I question the effectiveness of any and all neuroprotective drugs until double blind large trials have been completed.
Mark Kingston Levin PhD author of 30th Century series book 2 30th Century: Revived, which was release on Amazon April 29, 2018.
Dr. Levin won the IRWIN for the Best Science Fiction Book of 2017 for the first book in the series, 30th Century: Escape. To read the first three chapters, see www.markkingstonlevin.com.
For questions and comments write to Dr. Levin firstname.lastname@example.org
Dr. Levin was born and grew up in Vermont with many winters spent in Florida as a child. As a teenager he wrote poetry, served as a lifeguard and played football. He currently enjoys sailing, exploring underwater caves, snorkeling, writing science fiction and other pursuits. After working on the Apollo and Mars projects, he returned to school to study under Nobel Laureate Paul Dirac, obtaining his PhD in 2.5 years. Dr. Levin founded two companies and served the science policy apparatus in President Ford’s administration. He has been published over 44 times in scientific literature and was awarded over 32 US patents. The science fiction writer is now emerging with his first work, a trilogy titled 30th Century.
The first award-winning book, 30th Century: Escape, is currently available on Amazon both in its original erotic form BUY HERE and the new, toned-down General Audience Edition in both Kindle and in full-color print BUY PRINT HERE. Book two in the series, 30th Century: Revived, is available HERE in both e-book and print. Book 3 in the series, 30th Century: Contact, is now available HERE!
NEW: Your opportunity to be part of the process! If you sign up to be a Beta Reader, I will email you a copy of Book 3, 30th Century: Contact, in either PDF or Kindle. You read and tell me how you would make it stronger by sending an email to Dr. Levin email@example.com