University of Virginia scientists have identified a promising approach to delay aging by detoxifying the body of glycerol and glyceraldehyde, harmful by-products of fat that naturally accumulate over time.
The new findings come from UVA researcher Eyleen Jorgelina O’Rourke and her team. They are seeking to identify the mechanisms that drive healthy aging and longevity. Their new work suggests a potential way to do so by reducing glycerol and glyceraldehyde’s health-draining effects.
“The discovery was unexpected. We went after a very well-supported hypothesis that the secret to longevity was the activation of a cell-rejuvenating process named autophagy and ended up finding an unrecognized mechanism of health and lifespan extension,” said O’Rourke, of UVA’s Department of Biology and the UVA School of Medicine’s Department of Cell Biology.
O’Rourke said an exciting aspect of the discovery is that the keys to switch on the longevity mechanism are two enzymes that have been well studied because they detoxify the body of ethanol, the alcohol found in beer and bourbon.
“This existing knowledge greatly facilitates our search for drugs that can specifically activate this anti-aging process,” she said.
I'll be honest, even if what those mice received doubling their life span is for real, we're talking 20+ years of test and human trials before we can hope to get our hands on such at a minimum. The shots or pills will cost probably a million bucks per dose too. This is depending on politics as we have right wing fundies taking over a large part of our society at this moment that may find it playing god and ban it.
well yes, but...
these points are looking at the breakthroughs, not the base level advancements. Though I'd say even there there are a number of compounding factors.
For instance a gene therapy that extends life span is a big showy thing that needs to be longterm studied to see any side consequences like increasing cancer risks etc.
But increasing knowledge of metabolic processes from fasting, hyperbaric oxygen therapies, examples of saline dilution of blood (found to be as effective in some studies as 'young blood transfusion), and an increasing understanding of the sources and remedies of certain disease burdens (MS=EBV, etc). An increase in less systemically brutal cancer treatments with better 5 and 10 year survival rates, and advances in early detection (which the US healthcare system doesn't see as economically worth investment in, and may be why US life expectancy is doing worse). As well as a growing knowledge base about methodologies for increasing Healthspan.
These are also facing some degree of offset from increased burden of micro plastic, forever chemicals, general pollution, climate stress, nutrition and dietary stressors, poverty and political stressors. And increased disease exposure (Covid or even things like Lyme disease). But I suspect these things are not eating the entire gains we've made, as well as these are not sudden and new problems, they have been happening over generations and we have invested money and efforts to decrease and reverse these things with each year that goes by.
I think in the long run it'll be the incremental accumulation of progress toward indefinite longevity that will win us LEV before the viral showy breakthroughs. The discovery that existing diabetes medications have applications for improved cancer treatment and also trend toward longer lives in those who use them, rather than things like gene editing and new drugs. But lets not forget that it's better to get those showy, viral breakthroughs early so that their 20 years of follow up testing and trials take place during the added years we get from the less showy incidental improvements.
(I've recently had some renewed health issues that make me quite anxious that my lifespan is measured in years rather than decades left. But I was rather impressed to find the result of crunching some numbers. a adult male in the US who has reached age 45 has a rough 20% chance to live to see 92. That number declines as you add years to the top end, and making it to 100 is drastically reduced to insignificant numbers. But the numbers for the risk of that same person developing parkinsons in their lifetime are around 1%, dementia, most common cancer in men, etc all lower than the chance of making it to 92. Often multiple times lower. for those keeping track, a 45 year old man today has a 1 in five chance to live another 45 years and benefit from the development of treatments and medicine that will absolutely change those odds to even better numbers.)
University of Virginia scientists have identified a promising approach to delay aging by detoxifying the body of glycerol and glyceraldehyde, harmful by-products of fat that naturally accumulate over time.
The new findings come from UVA researcher Eyleen Jorgelina O’Rourke and her team. They are seeking to identify the mechanisms that drive healthy aging and longevity. Their new work suggests a potential way to do so by reducing glycerol and glyceraldehyde’s health-draining effects.
“The discovery was unexpected. We went after a very well-supported hypothesis that the secret to longevity was the activation of a cell-rejuvenating process named autophagy and ended up finding an unrecognized mechanism of health and lifespan extension,” said O’Rourke, of UVA’s Department of Biology and the UVA School of Medicine’s Department of Cell Biology.
O’Rourke said an exciting aspect of the discovery is that the keys to switch on the longevity mechanism are two enzymes that have been well studied because they detoxify the body of ethanol, the alcohol found in beer and bourbon.
“This existing knowledge greatly facilitates our search for drugs that can specifically activate this anti-aging process,” she said.
looking at the proposed mechanism for the effect as described in the article, I looked to see if there were lifestyle and dietary options for getting some degree of the proposed treatment. So far it looks like it's a bit of needle in a haystack but I did find - https://www.scientificamerican.com/arti ... -hangover/
Last year Chinese researchers from Sun Yat-sen University in China, the Food & Function paper co-authors, studied 57 different herbal and carbonated drinks' impacts on the enzymes that break down and rid the body of acetaldehyde and acetate, respectively. They discovered that some drinks, namely an herbal infusion called “Huo ma ren,” which consists of hemp seeds, increased ADH levels. That accelerated the breakdown of the alcohol in the first place but also inhibited the enzyme responsible for getting rid of acetate. The study showed that although green teas are rich in antioxidants, they “seriously prohibit” the metabolism of alcohol. The researchers wrote it’s better not to drink tea products during or after excessive alcohol consumption.
On the other hand, four beverages increased ADH and ALDH activity, helping to metabolize the toxins more quickly. Xue bi, which is similar to the popular soft drinks Sprite and 7-Up, showed the greatest increased ALDH activity and breakdown of acetaldehyde. The paper said the common soft drink additive taurine promotes efficient elimination of acetaldehyde. Thus, this research pointed toward Sprite or other soft drinks with taurine as being the optimal hangover cure.
Spoke too soon. Found something on affecting the activity of alcohol dehydrogenase (ADH) and/or aldehyde dehydrogenase (ALDH) enzymes through dietary sources.
product was developed (AHO) using pear (65%), sweet lime (25%) and coconut water (10%) and, validated for in vitro ADH and ALDH enzyme activities. AHO product was found to enhance ADH and ALDH activities by 23.31% and 70.02%, respectively.
onion and cheddar cheese seem to have come out as decent test results too. Black tea, and to a lesser degree green tea are also good options.
And not in the article but considering that alcohols are a natural product of food digestion and in their own right a food item, it would seem reducing alcohol consumption (though there is some question as to whether abstaining from alcohol can have a negative effect on ADH and ALDH, though not sure how verified that is) and also to a smaller degree sugars a simple carbs that can increase alcohol development during digestion, may help some of those factors.
Is 70 the new 60? New Research Suggests Humans Have Not Yet Reached Their Maximum Lifespan by Hillel Aron
March 29, 2023
Introduction:
(Courthouse News) — The oldest human believed to have ever lived was a French woman named Jeanne Calment. She was born in 1875, four years after the end of the Franco-Prussian War, and she died in 1997, having lived for 122 years and 164 days.
Calment may be an outlier, but some have wondered if humans have reached a ceiling on their maximum lifespan. Average life expectancy has been increasing for some time — though it has declined in recent years in some countries, including in the United States. But he oldest humans don't appear to be getting any older. Demographers call this trend in aging "compression." More humans are reaching middle and old age by avoiding various diseases and fatal acts of violence, but mortality amongst older people is steady.
But a new paper, published Wednesday in the journal PLOS ONE, argues the opposite.
"Cohorts born between around 1900 and 1950 are experiencing historically unprecedented mortality postponement, but are still too young to break longevity records," writes David McCarthy, an assistant professor at the University of Georgia. "As these cohorts attain advanced ages in coming decades, longevity records may therefore increase significantly."
"If there is a maximum limit to the human lifespan, we are not yet approaching it," he added.
There are approximately 30 trillion cells in a human body and our health is predicated on them properly interacting with and supporting each other, with the immune system playing a particularly pivotal role. One of the defining characteristics of aging is a decline in the proper functioning of our immune system. Centenarians, a rare population of individuals who reach 100 years or more, experience delays in aging-related diseases and mortality which suggests their immune systems remain functional into extreme old age.
Led by researchers from Boston University Chobanian & Avedisian School of Medicine and Tufts Medical Center, a new study finds centenarians harbor distinct immune cell type composition and activity and possess highly functional immune systems that have successfully adapted to a history of sickness allowing for exceptional longevity. These immune cells may help identify important mechanisms to recover from disease and promote longevity.
"Our data support the hypothesis that centenarians have protective factors that enable to recover from disease and reach extreme old ages," said lead author Tanya Karagiannis, Ph.D., senior bioinformatician, Center for Quantitative Methods and Data Science, Institute for Clinical Research and Health Policy Studies at Tufts Medical Center.
"We assembled and analyzed what is, to our knowledge, the largest single-cell dataset of centenarian subjects that allowed us to define unique features of this population that support the identification of molecular and lifestyle factors contributing to their longevity," explained senior author Stefano Monti, Ph.D., associate professor of medicine at the School of Medicine.
Extremely Rare Gene Variants Point to a Potential Cause of Age-related Macular Degeneration April 1, 2023
Introduction:
(EurekAlert) A study from the National Eye Institute (NEI) identified rare genetic variants that could point to one of the general mechanisms driving age-related macular degeneration (AMD), a common cause of vision loss in older adults. The variants generate malformed proteins that alter the stability of the membrane attack complex (MAC), which may drive a chronic inflammatory response in the retina. The findings, published in the journal iScience, point to MAC as a potential therapeutic target to slow or prevent the development of AMD. NEI is part of the National Institutes of Health.
There are many known genetic variants that raise or lower an individual’s risk of getting AMD; however, the contribution of each of these genetic changes to AMD is small.
To discover genetic variants – and proteins – with a direct tie to the disease, Anand Swaroop, Ph.D., chief of NEI’s Neurobiology, Neurodegeneration and Repair Laboratory, and lead author of the study, undertook a collaboration with Michael Klein, M.D., a leading AMD clinician at the Oregon Health Sciences University (OHSU), Portland. Klein has collected clinical information for hundreds of patients, as well as families with a high number of individuals with AMD. Swaroop, Klein and colleagues looked for families carrying very rare AMD-causing variants, where the effect of the gene variant is very strong, and where the variant directly affects protein structure and function. This type of rare variant can reveal the root cause of disease.
“While we have known about many genetic variants that affect AMD risk, only a few have pointed directly to protein alterations that can cause AMD,” said Swaroop. “By looking at large families with ultra-rare variants that track closely with disease across generations, we found two proteins that may directly be the driving force behind AMD pathology in affected patients. These proteins could be targets for future drugs.” While there are currently some treatments to slow vision loss for people with the wet form of AMD, there is no treatment for most patients and no cure for the disease.
Swaroop, Klein and colleagues found that in four families, individuals with AMD have mutations in one of two proteins that form one end of MAC: C8-alpha and C8-beta. The team found that the variants from the four AMD families all affected the ability of the C8 proteins to stick to each other, which may alter how MAC behaves in the eye’s retina.
The Green Mediterranean / High Polyphenols Diet Promotes Dramatic Proximal Aortic De-stiffening, Twice as Much as the Healthy Mediterranean Diet
Introduction:
(Eurekalert) BEER-SHEVA, Israel, April 17, 2023 – The green Mediterranean – high polyphenols diet substantially regresses proximal aortic stiffness (PAS), a marker of vascular aging and increased cardiovascular risk. The green Mediterranean diet was pitted against the healthy Mediterranean diet and a healthy guideline-recommended control diet in the DIRECT PLUS, a large-scale clinical intervention trial. Researchers found that the green Mediterranean diet regressed proximal aortic stiffness by 15%, the Mediterranean diet by 7.3%, and the healthy dietary guideline-directed diet by 4.8%.
The study was recently published in the top ranked journal in the field of Cardiology, JACC (Journal of the American College of Cardiology). This is the first time that scientists have presented a powerful, potent effect of diet on the age-related proximal aortic stiffness.
DIRECT PLUS was a large-scale, long term clinical trial over 18 months among 300 participants, which used MRIs to measure aortic stiffness, the most accurate noninvasive measure.
Aortic stiffness is a measure of the elasticity of the blood vessel wall, and it occurs when the elastic fibers within the arterial wall (elastin) begin to fray due to mechanical stress. Proximal aortic stiffness (PAS) reflects the aortic stiffness from the ascending to the proximal-descending thoracic aorta; the section of the aorta, the largest artery in the body that carries oxygen-rich blood away from the heart. Proximal aortic stiffness is a distinct marker of vascular aging and an independent cardiovascular risk factor to predict morbidity and mortality.
The research was led by Prof. Iris Shai of Ben-Gurion University of the Negev, Israel, an adjunct Professor from the Harvard School of Public Health and an honorary professor at the University of Leipzig, Germany, along with her PHD student Dr. Gal Tsaban, a cardiologist from Soroka University Medical Center, and colleagues from Harvard and Leipzig Universities.
Polyphenols are a category of compounds naturally found in plant foods, such as fruits, vegetables, herbs, spices, tea, dark chocolate, and wine.
They can act as antioxidants, meaning they can neutralize harmful free radicals that would otherwise damage your cells and increase your risk of conditions like cancer, diabetes, and heart disease.
Polyphenols are also thought to reduce inflammation, which is thought to be the root cause of many chronic illnesses.
Types of polyphenols
More than 8,000 types of polyphenols have been identified. They can be further categorized into 4 main groups.
• Flavonoids…
• Phenolic acids...
• Polyphenolic amides...
• Other polyphenols...
Possible ‘Steps’ to Revealing Super-agers April 17, 2023
Introduction:
(Eurekalert) On the quest for the proverbial fountain of youth, scientists have long looked for evidence of super-agers—people whose brain ages slower than their body. Researchers at the Del Monte Institute for Neuroscience at the University of Rochester have found older adults whose brain performance improves when they combine a cognitive task with walking.
“Identifying super-agers will leverage what we understand about the brain and aging,” said Eleni Patelaki, a Biomedical Engineering PhD student at the University of Rochester Medical Center and first author of the paper out today in NeuroImage. “But this is difficult to do because, in this case, there was no external evidence of this ability, and people are unaware that their brain is working differently.”
Walking and doing exposes brain flexibility
Researchers had the participants complete the same cognitive task while sitting and while walking. The 37 men and women, ages 62 to 79, scored similarly while sitting. When the same group repeated the test while walking, researchers found some individuals improved their cognitive performance. Researchers used Mobile Brain/Body Imaging (MoBI) to observe these changes and measure how the brain responded to the dual task. “We think this brain activity might constitute signatures of ‘super-aging,” said Patelaki. “We were able to find seven people, and now that we know where and how to look in the brain to find these super-agers, we can find more.”
The participants whose cognition improved while walking showed that their brain was able to adapt to and improve at the task—it had flexible usage of certain frontal resources. But those same people lost their flexibility in using the rest of their neural resources, similar to their peers who did not improve at the task while walking. This suggests that the brain’s ability to adapt or its flexibility in reallocating neural resources while walking might be an important factor in protecting cognition as we age.
Some young adult brains also improve
Previously, the same group of researchers in the Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory discovered that some young and healthy people also improve their performance on cognitive tasks while walking by changing the use of neural resources.
Human lifespan is related to the aging of our individual cells. Three years ago a group of University of California San Diego researchers deciphered essential mechanisms behind the aging process. After identifying two distinct directions that cells follow during aging, the researchers genetically manipulated these processes to extend the lifespan of cells.
As described in a new article published April 27, 2023, in Science, the team has now extended this research using synthetic biology to engineer a solution that keeps cells from reaching their normal levels of deterioration associated with aging.
Cells, including those of yeast, plants, animals and humans, all contain gene regulatory circuits that are responsible for many physiological functions, including aging. "These gene circuits can operate like our home electric circuits that control devices like appliances and automobiles," said Professor Nan Hao of the School of Biological Sciences' Department of Molecular Biology, the senior author of the study and co-director of UC San Diego's Synthetic Biology Institute.
However, the UC San Diego group uncovered that, under the control of a central gene regulatory circuit, cells don't necessarily age the same way. Imagine a car that ages either as the engine deteriorates or as the transmission wears out, but not both at the same time. The UC San Diego team envisioned a "smart aging process" that extends cellular longevity by cycling deterioration from one aging mechanism to another.
In the new study, the researchers genetically rewired the circuit that controls cell aging. From its normal role functioning like a toggle switch, they engineered a negative feedback loop to stall the aging process. The rewired circuit operates as a clock-like device, called a gene oscillator, that drives the cell to periodically switch between two detrimental "aged" states, avoiding prolonged commitment to either, and thereby slowing the cell's degeneration.
These advances resulted in a dramatically extended cellular lifespan, setting a new record for life extension through genetic and chemical interventions.
Human lifespan is related to the aging of our individual cells. Three years ago a group of University of California San Diego researchers deciphered essential mechanisms behind the aging process. After identifying two distinct directions that cells follow during aging, the researchers genetically manipulated these processes to extend the lifespan of cells.
As described in a new article published April 27, 2023, in Science, the team has now extended this research using synthetic biology to engineer a solution that keeps cells from reaching their normal levels of deterioration associated with aging.
Cells, including those of yeast, plants, animals and humans, all contain gene regulatory circuits that are responsible for many physiological functions, including aging. "These gene circuits can operate like our home electric circuits that control devices like appliances and automobiles," said Professor Nan Hao of the School of Biological Sciences' Department of Molecular Biology, the senior author of the study and co-director of UC San Diego's Synthetic Biology Institute.
However, the UC San Diego group uncovered that, under the control of a central gene regulatory circuit, cells don't necessarily age the same way. Imagine a car that ages either as the engine deteriorates or as the transmission wears out, but not both at the same time. The UC San Diego team envisioned a "smart aging process" that extends cellular longevity by cycling deterioration from one aging mechanism to another.
In the new study, the researchers genetically rewired the circuit that controls cell aging. From its normal role functioning like a toggle switch, they engineered a negative feedback loop to stall the aging process. The rewired circuit operates as a clock-like device, called a gene oscillator, that drives the cell to periodically switch between two detrimental "aged" states, avoiding prolonged commitment to either, and thereby slowing the cell's degeneration.
These advances resulted in a dramatically extended cellular lifespan, setting a new record for life extension through genetic and chemical interventions.
A new study published on eLife and led by the Institute for Evolutionary Biology (IBE, CSIC-UPF) and the IRB Barcelona, has revealed that the Chinmo gene is responsible for establishing the juvenile stage in insects. It also confirms that the Br-C and E93 genes play a regulatory role in insect maturity. These genes, which are also present in humans, act as a promoter and as a suppressor, respectively, of cancerous processes.
The results of the research, which was carried out with the fruit fly Drosophila melanogaster and the cockroach Blatella germanica, reveal that these genes have been conserved throughout the evolution of insects. Therefore, it is believed that they could play a key role in the evolution of metamorphosis.
