Deadly Diets

Carbon copied corn
lines up to fill the shelves,
a litany of yellow
mangled into
nauseating rainbows
of our globalised excess.
Colours of artifice,
carefully arranged
to catch the eye:
hydrogenation,
moulding,
dyes,
stabilising,
flavours,
lies.
Nutrients torn from the cob,
leaving open wounds
filled with greenbacks
across a land
that could have lasted
forever.

A selection of ultra-processed foods that now make up our globalised diet (Image Credit: Nico Smit/ Unsplash).

This poem is inspired by recent research, which has found that a globalised diet that increasingly includes ultra-processed foods is having a negative impact on both human and planetary health.

Ultra-processed foods are those foods that go through multiple processes (e.g. extrusion, moulding, milling), contain many added ingredients, and are highly manipulated. Examples include soft drinks, candy, ice-cream, packaged soups, chicken nuggets, and ready meals. These types of food are less filling and raise our blood sugars higher than minimally processed foods. They are also generally higher in calories and sugar, lower in protein and fibre, and are associated with higher risks of obesity, heart disease and stroke, type-2 diabetes, cancer, frailty, depression, and death. Yet despite the fact that ultra-processed foods are so obviously bad for human consumption, they are now the basis of our globalised diet, becoming dominant in the global food supply, with sales and consumption growing in all regions and almost all countries.

In this new study, researchers highlight how this lack of diversity is not only having a negative impact on human health. As a result of dietary patterns worldwide becoming increasingly more processed and less diverse, the planet’s agrobiodiversity (i.e. the variety and variability of animals, plants, and microorganisms used directly or indirectly for food and agriculture) is also diminishing. Today, 90% of humanity’s energy intake comes from just 15 crop plants, and more than four billion people rely on just three of them: rice, wheat, and maize. This lack of agrobiodiversity is bad because it reduces the gene pool, thereby making it harder for agriculture to adapt to global environmental changes such as climate change and desertification. Furthermore, ultra-processed food production uses large quantities of land, water, energy, herbicides, and fertilisers, causing further environmental degradation in addition to the accumulation of unnecessary packaging waste. As such, this new globalised diet is severely damaging both the humans that consume it and the environments that are used to produce it. This study concludes that researchers and policymakers need to highlight the destruction of agrobiodiversity caused by ultra-processed foods, and to agree on policies and actions designed to slow and reverse this disaster.

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New AI-driven algorithm can detect autism in brain ‘fingerprints’

Stanford researchers have developed an algorithm that may help discern if someone has autism by looking at brain scans. The novel algorithm, driven by recent advances in artificial intelligence (AI), also successfully predicts the severity of autism symptoms in individual patients. With further honing, the algorithm could lead to earlier diagnoses, more targeted therapies, and broadened understanding of autism’s origins in the brain.

The algorithm pores over data gathered through functional magnetic resonance imaging (fMRI) scans. These scans capture patterns of neural activity throughout the brain. By mapping this activity over time in the brain’s many regions, the algorithm generates neural activity “fingerprints.” Although unique for each individual just like real fingerprints, the brain fingerprints nevertheless share similar features, allowing them to be sorted and classified.

As described in a new study published in Biological Psychiatry, the algorithm assessed brain scans from a sample of approximately 1,100 patients. With 82% accuracy, the algorithm selected out a group of patients whom human clinicians had diagnosed with autism.

“Although autism is one of the most common neurodevelopmental disorders, there is so much about it that we still don’t understand,” says lead author Kaustubh Supekar, a Stanford clinical assistant professor of psychiatry and behavioral sciences and Stanford HAI affiliate faculty. “In this study, we’ve shown that our AI-driven brain ‘fingerprinting’ model could potentially be a powerful new tool in advancing diagnosis and treatment.”

Unlike many other diseases, autism lacks objective biomarkers—telltale measurements that reveal a medical condition’s presence and sometimes severity—meaning there is no simple test for the disorder. Instead, diagnosis is based on observing patients’ behaviors, which are naturally highly variable and thus make diagnosis a challenge. (Common signs of autism include difficulty navigating everyday social interaction, deficits in communicating and learning, and repetitive speech and motions.)

“We need to create objective biomarkers for autism,” says Supekar, “and brain fingerprints get us one step closer.”

Combining Big Data and XAI

Scientists have long searched for biomarkers via fMRI scans. Yet studies to date with small populations have reported conflicting results, stemming from natural variability in patients’ brains and confounded further by differences in fMRI machines and testing methods.

Like many scientific fields, autism research has embraced the big data approach, Supekar says, where previously unobtainable insights emerge from analyzing large, statistically powerful samples. Supekar’s new study is a case in point, pooling brain scans from medical centers worldwide into a mammoth, demographically and geographically diverse dataset.

The next step was to effectively parse and deal with the data complexity and variability. Supekar and colleagues thought a good place to start would be image recognition algorithms, developed by technology companies. These algorithms have grown increasingly sophisticated at handling significant degrees of variability in the images they assess.

For example, Supekar says, imagine an algorithm designed to identify cats and dogs in online images. That algorithm must contend with the animals being photographed from different angles and distances, as well as nimbly account for the ranges of colors and features among breeds.

“For image recognition AI to be successful, it doesn’t matter if my 5-year-old took the picture or someone with an award in photography—the algorithm has to work in both cases,” says Supekar. “The same kind of heterogeneity you get in pictures of cats and dogs, you get in brain scans, too.”

In deriving their image-recognition algorithms, Supekar and colleagues sought to make the artificial intelligence explainable, or understandable to human researchers. Researchers in recent years have focused on crafting explainable AI, or XAI, in contrast to conventional AI systems that might produce quality results but not in readily apparent ways.

“A challenge has been that AI algorithms can be a ‘black box,’ where we can’t explain where the accuracy of the algorithm comes from,” says Supekar.

Taking the cat-versus-dog example model again, researchers would want to know if the algorithm is picking over the animals’ facial features or neck sizes, say. For the brain fingerprinting algorithm, Supekar and colleagues fashioned a simple mathematical model that assesses brain regional interactions and interconnectivity. In this manner, the XAI algorithm alit upon three brain regions exhibiting significant differences in interconnectivity in a groupable portion of the dataset.

Lending credibility to the XAI algorithm’s findings, those three brain regions have been previously implicated in autism pathology. The regions are the posterior cingulate cortex and precuneus, which form part of the default mode network (DMN), notably active during periods of wakeful rest; the dorsolateral and ventrolateral prefrontal cortex, involved in cognitive control; and the superior temporal sulcus, involved in processing the sounds of human voices. In particular, disruptions to the DMN served as strong predictors of autism symptom severity in the studied population.

Earlier the Better

While the XAI algorithm performed admirably at this early stage of development, Supekar and colleagues will need to improve its accuracy further still to raise brain fingerprinting to the level of a definitive biomarker. The researchers intend to explore the algorithm’s efficacy in sibling studies, where one sibling has autism and the other does not, to hone the ability to detect fine-tuned, yet critical differences between potentially very similar brains.

Supekar envisions brain fingerprinting being used to assess the brains of very young children, perhaps as early as 6 months or a year old, who are at high risk of developing autism. Earlier diagnosis is critical in achieving better outcomes, with therapies proving more effective when introduced while patients are still toddler-aged versus later in childhood

“We hope that the approach demonstrated in our study could diagnose autism during the window of opportunity when interventions are maximally most effective,” says Supekar.

Stanford HAI’s mission is to advance AI research, education, policy and practice to improve the human condition. Learn more. 

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Covid Lockdowns Hurt Mental Health of Women in the Developing World

While potentially crucial to preventing the spread of COVID-19, lockdowns are associated with increased rates of depression and anxiety as well as food insecurity among women in India and other parts of the developing world, according to a new research.

The study from the University of California San Diego’s School of Global Policy and Strategy finds that women whose social position may make them more vulnerable – those with daughters and those living in female-headed households – experienced even larger declines in mental health as a result of lockdowns.

The paper, to be published in a forthcoming issue of the Journal of Economic Development, surveyed 1,545 households over the phone in various rural regions throughout Northern India. The surveys took place in fall 2019, before the pandemic and in August 2020, near the height of the first COVID-19 wave in India. Certain villages and districts had varying containment policies, which allowed the researchers to compare health outcomes of women who experienced lockdowns for several months to those who experienced zero levels of lockdowns.

The authors took many factors into consideration in their analysis including COVID cases, hospitalizations and deaths from the novel coronavirus.

For surveyed women, moving from zero to average levels of lockdowns is associated with a 38 percent increase in depression, a 44 percent increase in anxiety and a 73 percent increase in exhaustion.

“Not having access to access to work and socialization outside the home can be very detrimental for women’s mental health in developing countries,” said study co-author Gaurav Khanna, assistant professor of economics at the School of Global Policy and Strategy.

The pandemic resulted in dramatic losses of income for women. In the survey, roughly 25 percent of households reduced the number of meals consumed, compared to a normal month. However, these declines primarily impacted women because in many cultures throughout the developing world, women’s food intake is the first be limited when food is scarce.

“We wanted to know the impact lockdown policies have on women in lower-income countries where there may be limited social safety nets to absorb these shocks,” Khanna added.  “As we found in our study, the consequences of lockdown policies are exacerbated for women. We hope policymakers in developing countries and beyond know what the implications are for these policies, especially for those in vulnerable positions because if there is another wave, communities could be faced with similar lockdowns.”

The paper outlines policy recommendations that could help address the mental and physical health consequences experienced by women during the pandemic.

“Policymakers should consider what supportive measures are necessary to limit economic devastation from lockdowns and they should target aid, particularly access to food, to vulnerable households and women,” the authors note.

For example, in certain parts of India, the government did distribute food to rural areas, which helped prevent malnutrition and food insecurity.

Counseling and helpline services offered over-the-phone can also help address the pandemic’s mental health impacts, the authors noted.

While the findings focus on the developing world, they have implications for women all over the world who experience lockdowns.

“We suspect the impact in the U.S. on women and mothers in particular was also exacerbated,” Khanna said. “When kids are not in school, or daycare, the burden usually falls on women because of traditional gender roles with child care. Policymakers should be cognizant of the fact that women are going to be impacted differently by these policies.”

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Estrogen-regulated brain circuit helps females control obesity

Before menopause, women are typically protected from metabolic problems that may lead to weight gain, when compared to age-matched men. However, after menopause, this benefit seems to disappear. Researchers around the world agree that the female hormone estrogen is one important player in this benefit.

At Baylor College of Medicine, Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology, and his colleagues worked with an animal model to investigate how estrogen contributes to maintaining energy balance and weight control from the brain’s point of view.

An estrogen-activated brain circuit

“My lab has long been interested in understanding sex differences in metabolic control,” Xu said. “In previous work, we showed that one of the estrogen receptors, ER-alpha, is expressed in several brain regions, including the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH).”

When v1VMH neurons expressing ER-alpha respond to estrogen, the animals increase their heat production or thermogenesis and physical activity. Both responses are beneficial as they increase energy expenditure, which can prevent obesity.

“What we didn’t know at that time were the neurocircuits that mediate these responses,” Xu said. “Using modern neuroscience technology, we identified a neurocircuit that connects ER-alpha-expressing neurons in the vlVMH region with serotonin-producing neurons located in another brain region called dorsal raphe nucleus (DRN).

“We confirmed that estrogen-mediated activation of this circuit actually stimulates thermogenesis and physical activity.”

The researchers also found that the circuit responds to changes in ambient temperature and in the nutritional status of the animal.

“For example, the circuit can be activated when the environment is cold, stimulating thermogenesis and physical activity, which would help the animal stay warm,” Xu said. “The circuit can be inhibited when the animal is hungry, which would shut down thermogenesis and physical activity, saving energy to adapt to the lack of nutrients.”

Xu and his colleagues studied this circuit in females, but also in males. The team found that the circuit is conserved in males – they have the same neurons that express ER-alpha and project into the same downstream brain regions.

“If the circuit is artificially activated in males, the same responses occur – thermogenesis and physical activity are stimulated,” Xu said. “However, we still don’t know the role this circuit plays in males. Further studies will help answer this question.”

Find all the details of this study in the journal Science Advances.

Other contributors to this research are Hui Ye, Bing Feng, Chunmei Wang, Kenji Saito, Yongjie Yang, Lucas Ibrahimi, Sarah Schaul, Nirali Patel, Leslie Saenz, Pei Luo, Penghua Lai, Valeria Torres, Maya Kota, Devin Dixit, Xing Cai, Na Qu, Ilirjana Hyseni, Kaifan Yu, Yuwei Jiang, Qingchun Tong, Zheng Sun, Benjamin R. Arenkiel, Yanlin He and Pingwen Xu. The authors are affiliated with Baylor College of Medicine, the University of Illinois at Chicago, Louisiana State University System or the University of Texas Health Science Center at Houston.

This work was supported by the following grants from National Institutes of Health: P01 DK113954, R01DK117281, R01 DK115761, R01739 DK125480; R01 DK120858, R00 DK107008, R01 DK123098, K01740 DK119471; K01 DK111771; P20 GM135002; R01 DK114279, R21 NS108091, R01 DK109934; Q01ES027544 and R03AG070687. Further support was provided by USDA/CRIS (51000-064-01S), DOD (Innovative Grant W81XWH-19-PRMRP-DA.; DOD W81XWH 9-1-0429), DRTC (The Pilot and Feasibility Award DK020595), and the American Diabetes Association (1-17-PDF-138).

By Ana María Rodríguez, Ph.D.

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Researchers generate the first complete, gapless sequence of a human genome

Scientists have published the first complete, gapless sequence of a human genome, two decades after the Human Genome Project produced the first draft human genome sequence. According to researchers, having a complete, gap-free sequence of the roughly 3 billion bases (or “letters”) in our DNA is critical for understanding the full spectrum of human genomic variation and for understanding the genetic contributions to certain diseases. The work was done by the Telomere to Telomere (T2T) consortium, which included leadership from researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; University of California, Santa Cruz; and University of Washington, Seattle. NHGRI was the primary funder of the study.

Analyses of the complete genome sequence will significantly add to our knowledge of chromosomes, including more accurate maps for five chromosome arms, which opens new lines of research. This helps answer basic biology questions about how chromosomes properly segregate and divide. The T2T consortium used the now-complete genome sequence as a reference to discover more than 2 million additional variants in the human genome. These studies provide more accurate information about the genomic variants within 622 medically relevant genes.

“Generating a truly complete human genome sequence represents an incredible scientific achievement, providing the first comprehensive view of our DNA blueprint,” said Eric Green, M.D., Ph.D., director of NHGRI. “This foundational information will strengthen the many ongoing efforts to understand all the functional nuances of the human genome, which in turn will empower genetic studies of human disease.”

The now-complete human genome sequence will be particularly valuable for studies that aim to establish comprehensive views of human genomic variation, or how people’s DNA differs. Such insights are vital for understanding the genetic contributions to certain diseases and for using genome sequence as a routine part of clinical care in the future. Many research groups have already started using a pre-release version of the complete human genome sequence for their research.

The full sequencing builds upon the work of the Human Genome Project, which mapped about 92% of the genome, and research undertaken since then. Thousands of researchers have developed better laboratory tools, computational methods and strategic approaches to decipher the complex sequence. Six papers encompassing the completed sequence appear in Science(link is external), along with companion papers in several other journals.

That last 8% includes numerous genes and repetitive DNA and is comparable in size to an entire chromosome. Researchers generated the complete genome sequence using a special cell line that has two identical copies of each chromosome, unlike most human cells, which carry two slightly different copies. The researchers noted that most of the newly added DNA sequences were near the repetitive telomeres (long, trailing ends of each chromosome) and centromeres (dense middle sections of each chromosome).

“Ever since we had the first draft human genome sequence, determining the exact sequence of complex genomic regions has been challenging,” said Evan Eichler, Ph.D., researcher at the University of Washington School of Medicine and T2T consortium co-chair. “I am thrilled that we got the job done. The complete blueprint is going to revolutionize the way we think about human genomic variation, disease and evolution.”

The cost of sequencing a human genome using “short-read” technologies, which provide several hundred bases of DNA sequence at a time, is only a few hundred dollars, having fallen significantly since the end of the Human Genome Project. However, using these short-read methods alone still leaves some gaps in assembled genome sequences. The massive drop in DNA sequencing costs comes hand-in-hand with increased investments in new DNA sequencing technologies to generate longer DNA sequence reads without compromising the accuracy.

Over the past decade, two new DNA sequencing technologies emerged that produced much longer sequence reads. The Oxford Nanopore DNA sequencing method can read up to 1 million DNA letters in a single read with modest accuracy, while the PacBio HiFi DNA sequencing method can read about 20,000 letters with nearly perfect accuracy. Researchers in the T2T consortium used both DNA sequencing methods to generate the complete human genome sequence.

“Using long-read methods, we have made breakthroughs in our understanding of the most difficult, repeat-rich parts of the human genome,” says Karen Miga, Ph.D., a co-chair of the T2T consortium whose research group at the University of California, Santa Cruz is funded by NHGRI. “This complete human genome sequence has already provided new insight into genome biology, and I look forward to the next decade of discoveries about these newly revealed regions.”

According to consortium co-chair Adam Phillippy, Ph.D., whose research group at NHGRI led the finishing effort, sequencing a person’s entire genome should get less expensive and more straightforward in the coming years.

“In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their healthcare,” Phillippy said. “Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.”

Many early-career researchers and trainees played pivotal roles, including researchers from Johns Hopkins University, Baltimore; University of Connecticut, Storrs; University of California, Davis; Howard Hughes Medical Institute, Chevy Chase, Maryland; and the National Institute of Standards and Technology, Gaithersburg, Maryland. The package of six papers reporting this accomplishment appears in today’s issue of Science, along with companion papers in several other journals.

For more, visit Genome.gov/T2T(link is external) and follow @Genome_gov(link is external).

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NIH begins clinical trial evaluating second COVID-19 booster shots in adults

A Phase 2 clinical trial evaluating various additional COVID-19 booster shots has begun enrolling adult participants in the United States. The trial aims to understand if different vaccine regimens—prototype and variant vaccines alone and in combinations—can broaden immune responses in adults who already have received a primary vaccination series and a first booster shot. The study, known as the COVID-19 Variant Immunologic Landscape (COVAIL) trial, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

“We are looking beyond the Omicron variant to determine the best strategy to protect against future variants,” said NIAID Director Anthony S. Fauci, M.D. “This trial will help us understand if we can use prototype and variant vaccines alone or together to shift immune responses to cover existing and emerging COVID-19 variants.”

Despite waning protection against infection and mild illness during the Omicron wave, COVID-19 vaccines available in the United States so far have maintained durable protection against severe COVID-19. However, NIAID is preparing for the possibility of future variants evading protection against currently available COVID-19 vaccines.

COVID-19 vaccine manufacturers can adjust prototype vaccines to target specific variants, a process similar to how manufacturers update seasonal influenza vaccines every year to target circulating strains. However, predicting if, when and where new COVID-19 variants will emerge and how they will affect the population, remains challenging. Studies(link is external) indicate that Omicron has a combination of mutations that make it substantially different from prior SARS-CoV-2 variants. Should a new variant emerge that more closely resembles ancestral SARS-CoV-2 or, for example, the Delta variant, an Omicron-specific vaccine may not offer substantial protection. An individual’s response to booster shots may also be impacted by their history of prior infection and vaccination, or both, and what type of COVID-19 vaccines they received.

Vaccine manufacturers have previously studied some variant vaccine candidates and are currently conducting clinical trials of Omicron-specific vaccines. The COVAIL trial will gather data on the immune responses induced by prototype vaccines and variant vaccine candidates—including bivalent vaccines, which target two SARS-CoV-2 variants—to inform booster shot recommendations.

Nadine Rouphael, M.D., director of the Hope Clinic at the Emory Vaccine Center in Atlanta, and Angela Branche, M.D., associate professor of medicine at the University of Rochester Medical Center in New York, are leading the trial. Site investigators at 24 clinics are enrolling 600 participants 18 years and older who already have received a primary COVID-19 vaccination series and booster shot. Participants are randomly assigned to one of six vaccine regimens:

1. One 50-microgram (mcg) injection of the mRNA-1273 (Spikevax) prototype vaccine, which is the same vaccine currently authorized in the United States as a booster shot for adults
2. One 50-mcg injection consisting of mRNA-1273.351 (an investigational vaccine targeting the Beta variant) and mRNA-1273.529 (an investigational vaccine targeting the Omicron variant)
3. Two vaccinations administered two months apart: each vaccination is one 50-mcg injection containing both mRNA-1273.351 and mRNA-1273.529
4. One 50-mcg injection consisting of mRNA-1273.617.2 (an investigational vaccine targeting the Delta variant) and mRNA-1273.529
5. One 50-mcg injection of mRNA-1273.529
6. One 50-mcg injection consisting of mRNA-1273 (Spikevax) and mRNA-1273.529

The first stage of this trial is being conducted in collaboration with Moderna, Inc., based in Cambridge, Massachusetts, and Moderna is manufacturing the study vaccines that will be administered. The trial will be adapted to enroll more participants to evaluate additional vaccine platforms and variant vaccines from other manufacturers as needed to further inform public health decisions. Participants will be monitored for symptoms and adverse events following vaccination and will be asked to return to the clinic during set times over the course of 12-14 months to provide blood samples. Investigators will evaluate the samples in the laboratory to measure and characterize immune responses to SARS-CoV-2 strains. Investigators aim to have initial findings available by August 2022.

The study is being conducted in collaboration with academic medical centers across the U.S., NIAID’s Infectious Diseases Clinical Research Consortium (IDCRC) and the NIAID SARS-CoV-2 Assessment of Viral Evolution (SAVE) Program. For more information about the trial, including specific site locations, and for details on how to participate, please visit clinicaltrials.gov and search identifier NCT05289037. The trial is funded through a contract to Frederick National Laboratory for Cancer Research, operated by Leidos Biomedical Research (75N91019D00024) in Frederick, Maryland. The IDCRC’s protocol development work is supported by cooperative agreement UM1AI148684.

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GlyNAC improves biomarkers in humans and extends lifespan in rodents

Antioxidants proved a bust for life extension almost 25 years ago, but glutathione stands out as an exception. We lose glutathione as we age, and supplementing to increase glutathione levels has multiple benefits, possibly on lifespan.

Glutathione is manufactured in the body via an ancient mechanism taking as input cysteine, glutamic acid, and glycine. Supplementing N-Acetyl Cysteine (NAC) and glycine are independently associated with health benefits, and possibly increased lifespan. Glutamine seems to be in adequate supply for most of us.

Each cell manufactures its own glutathione. (GSH is an abbreviation for the reduced form of glutathione.) Concentrations of GSH within a cell a typically 1,000-fold higher than in blood plasma. When we look for glutathione deficiency, we measure the blood level, because that is convenient. It is much harder to measure intracellular levels of GSH. These two studies [2011, 2013] demonstrated that intracellular levels decline with age more consistently and more severely than blood levels. People in their 70s have less than ¼ the glutathione (in red blood cells) that they had when they were in their 20s. The same study also found that intracellular levels of cysteine and glycine but not glutamate decline with age.

Supplementing with NAC is already known to boost glutathione levels. But here is a motivation to try a combination of glycine and NAC, dubbed “GlyNAC” to see if we can do even better. This work has been spearheaded by Rajagopal Sekhar.

In humans, “Supplementing GlyNAC for a short duration of 2 wk corrected the intracellular deficiency of glycine and cysteine, restored intracellular GSH synthesis, corrected intracellular GSH deficiency, lowered OxS, improved MFO, and lowered insulin resistance.” [Sekhar] Most of these benefits are theoretical. Lowering oxidation levels is a double-edged sword. MFO=mitochondrial fatty acid oxidation, and this benefit is on firmer footing. Membranes are made of fatty acids, and mitochondrial efficiency, like most everything in the body, depends on highly selective membranes. The crowning benefit is improved insulin sensitivity, and we can be fairly confident this leads to longer healthspan.

The two recent studies, in humans and mice, are indeed impressive.

The small human study found that “GlyNAC supplementation for 24 weeks in OA corrected RBC-GSH deficiency, OxS, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin-resistance, genomic-damage, cognition, strength, gait-speed, and exercise capacity; and lowered body-fat and waist-circumference.” Though they didn’t measure methylation age, this constellation of improvements gives us confidence that people were looking and acting younger.

In older (71-80 yo) subjects 24 weeks of GlyNAC supplementation raised intracellular GSH levels from 0.4 mmol to 1.2, compared to 1.8 in young adults. (Levels were measured in red blood cells.)

Two central players in aging are inflammation and insulin resistance; both showed excellent response.

Inflammation decreased markedly: Average C-reactive protein (CRP) dropped from 4.9 to 3.2 (compared to 2.4 for young people). IL-6 dropped from 4.8 to 1.1 (ref 0.5 for young). TNFα dropped from 98 to 59 (ref 45).

Insulin resistance fell just as dramatically, along with fasting glucose and plasma insulin.

Cognitive performance improved markedly! as did grip strength, endurance, and gait speed.

GlyNAC subjects lost a lot of weight — 9% of body weight in 24 weeks. This is both very good news and a hint that some of the benefits of GlyNAC may be caloric restriction mimetic effects, indirectly due to suppression of appetite or of food absorption.

Is all this evidence of a decrease in biological age?

But the effects faded weeks after the treatment stopped. This, I believe, is different from resetting methylation age. There is not a lot of data yet to test this, but I believe that methylation is close to the source of aging; in other words, the body senses its age by its epigenetic state, and adjusts repair and protection levels accordingly. Thus changing epigenetics to a younger state, IMO, effectively induces an age change in the body.

If this is correct, then my guess is that GlyNAC does not set back methylation age, based on the fact that the effects must be continually renewed by daily doses of glycine and NAC. On the other hand, mitochondria are such a central player in expressing multiple symptoms of aging that it may well be that continuous treatment with GlyNAC leads to longer lifespan.

…and indeed that is what was just reported in a mouse study. 16 mice lived 24% longer with GlyNAC supplementation, compared to 16 controls. 24% is impressive (see table below). For example, rapamycin made headlines a decade ago with an average lifespan increase of 14%. (In other studies, rapamycin was associated with even greater life extension.) The winner in this table is a Russian pineal peptide, which claims 31% increase in lifespan. I have previously bemoaned the fact that this eye-popping work from the St Petersburg laboratories of Anisimov and Khavinson has not been replicated in the West (though Russian peptides are now commercialized in he West). 

Table source: https://ift.tt/uB6TMaU
(This is a sample — not a complete list.)

Treatment	Lifespan increase
Epithalamin	31%
Thymus Peptide	28%
Rapamycin	26%
N-Acetylcysteine	24%
GlyNAC 2022	24%
Spermidine	24%
Acarbose	22%
Phenformin	21%
Ethoxyquin	20%
Vanadyl sulfate	12%
Aspirin	8%

An asterisk must be placed next to the new 24% life extension from GlyNAC. Eleven years ago, Flurkey, found the same 24% life extension with NAC alone. NAC supplementation without glycine is known to increase glutathione production. Do we need glycine in addition, or is cysteine the bottleneck? Levels of both free glycine and cysteine decline with age. This would suggest that supplementation of both should be more effective than supplementing NAC alone. But I was unable to find any study that asked whether GSH levels are raised to a greater extent by GlyNAC than by NAC alone.

Glycine supplementation in large amounts mimics methionine restriction, which is a known but impractical life extension strategy.

If you decide to take glycine, it should be at bedtime, and in large amounts, a teaspoon or two. (I did this for awhile using glycine as a sweetener in hot chocolate soymilk, until I decided it ruined the taste of the chocolate drink. Whether this is a sound reason for tailoring an anti-aging agenda I’ll leave you to decide.)

All this work comes out of the laboratory of Rajagopal V. Sekhar at Baylor College of Medicine in Texas. It’s time that a broader life extension community joined in the action. I’m grateful to Dr Sekhar for commenting on earlier drafts of this article.

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