Biohacking The Oral Microbiome: Test #2

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Papers referenced in the video:
Nitrate as a potential prebiotic for the oral microbiome
https://pubmed.ncbi.nlm.nih.gov/32732931/

The Importance of Nitrate Reduction for Oral Health
https://pubmed.ncbi.nlm.nih.gov/35196931/

Nitrate and nitrite content of vegetables, fruits, grains, legumes, dairy products, meats and processed meats
https://www.sciencedirect.com/science/article/abs/pii/S0889157516300795

Nitrate in vegetables Scientific Opinion of the Panel on Contaminants in the Food chain
https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2008.689

Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease
https://pubmed.ncbi.nlm.nih.gov/33652903/

Efficacy of β-caryophyllene for periodontal disease related factors
https://pubmed.ncbi.nlm.nih.gov/30826504/

Synergistic effect between clove oil and its major compounds and antibiotics against oral bacteria
https://pubmed.ncbi.nlm.nih.gov/21397894/

Resting Heart Rate And Heart Rate Variability: What’s Optimal, 1,502 Days of Data

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Papers referenced in the video:
Biological aging of human body and brain systems
https://www.medrxiv.org/content/10.1101/2022.09.03.22279337v1

Relation of high heart rate variability to healthy longevity
https://pubmed.ncbi.nlm.nih.gov/20381674/

Heart Rate Variability and Exceptional Longevity
https://pubmed.ncbi.nlm.nih.gov/33041862/

Inter- and intraindividual variability in daily resting heart rate and its associations with age, sex, sleep, BMI, and time of year: Retrospective, longitudinal cohort study of 92,457 adults
https://pubmed.ncbi.nlm.nih.gov/32023264/

Heart rate variability with photoplethysmography in 8 million individuals: a cross-sectional study
https://pubmed.ncbi.nlm.nih.gov/33328029/

Blood Test #5 in 2022: Supplements, Diet

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Papers referenced in the video:
Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies
https://pubmed.ncbi.nlm.nih.gov/31069230/

Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey
https://pubmed.ncbi.nlm.nih.gov/10075334/

Risk Factors For Hyperuricemia In Chinese Centenarians And Near-Centenarians
https://pubmed.ncbi.nlm.nih.gov/31908434/

DHEA-S Is A Weakness In My Data: Blood Test #5 in 2022

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Papers referenced in the video:
Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults
https://pubmed.ncbi.nlm.nih.gov/30733566/

The Value of Serum Albumin and High-Density Lipoprotein Cholesterol in Defining Mortality Risk in Older Persons with Low Serum Cholesterol
https://pubmed.ncbi.nlm.nih.gov/11559371/

Reference intervals of nine steroid hormones over the life-span analyzed by LC-MS/MS: Effect of age, gender, puberty, and oral contraceptives
https://pubmed.ncbi.nlm.nih.gov/31201927/

Incomplete Pattern of Steroidogenic Protein Expression in Functioning Adrenocortical Carcinomas
https://pubmed.ncbi.nlm.nih.gov/32751564/

Serum dehydroepiandrosterone sulfate levels predict longevity in men: 27-year follow up study in a community based cohort (Tanushimaru study)
https://pubmed.ncbi.nlm.nih.gov/18422949/

Quantifying Biological Age: Blood Test #5 in 2022

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Papers referenced in the video:
A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study
https://pubmed.ncbi.nlm.nih.gov/30596641/

Underlying features of epigenetic aging clocks in vivo and in vitro
https://pubmed.ncbi.nlm.nih.gov/32930491/

Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants
https://pubmed.ncbi.nlm.nih.gov/33684206/

Population Specific Biomarkers of Human Aging: A Big Data Study Using South Korean, Canadian, and Eastern European Patient Populations
https://pubmed.ncbi.nlm.nih.gov/29340580/

The Excel file to calculate Levine’s Biological Age is embedded in this link from my website:
https://michaellustgarten.com/2019/09/09/quantifying-biological-age/

Ending Age-Related Diseases 2022 Conference Presentation

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Epigenetic Tests #1 and 2: Horvath, Hannum, DunedinPACE

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Papers referenced in the video:
Underlying features of epigenetic aging clocks in vivo and in vitro
https://pubmed.ncbi.nlm.nih.gov/32930491/

DNA methylation‐based measures of biological age: meta‐analysis predicting time to death
https://pubmed.ncbi.nlm.nih.gov/27690265/

Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring
https://pubmed.ncbi.nlm.nih.gov/26678252/

DunedinPACE, a DNA methylation biomarker of the pace of aging
https://pubmed.ncbi.nlm.nih.gov/35029144/

Effect of Long-Term Caloric Restriction on DNA Methylation Measures of BiologicalAging in Healthy Adults: CALERIE™ Trial Analysis
https://www.medrxiv.org/content/10.1101/2021.09.21.21263912v1.full.pdf

Glycine + N-Acetyl Cysteine Supplementation Increases Lifespan (Video Transcript)

Glutathione declines during aging. To illustrate that point, let’s take a look at 3 different studies.

First, when comparing people in the 21 to 61y+ age range, blood GSH levels declined by about 50% (Yang et al. 1995). Second, 70yr olds have 15% less glutathione when compared with newborns (Inal et al. 2002). Third, GSH was 33% reduced when comparing the youngest group, 20-29y, vs the oldest, > 60y (Qui-lin et al. 2005).

With these data in mind, can restoring glutathione levels in older adults improve health-related measures?

To optimize GSH, first we need to know what it’s made of. Glutathione is a tripeptide, which means that it’s made from 3 amino acids, including cysteine, glycine, and glutamate. When considering that glycine and cysteine levels (in blood) decline during aging (Sekhar et al. 2011), strategies aimed at restoring levels of these amino acids may be an important approach for restoring GSH in GSH-deficient older adults.

In 2021, Kumar et al. utilized this approach in a a relatively small (8 older adults, 71-80y, 8 younger adults, 21-30y), 24-week randomized controlled trial (RCT), and found that glycine + N-acetylcysteine (NAC, as a source of cysteine) supplementation (100 mg each for glycine and NAC/kg body weight) impacted multiple health-related parameters, including GSH restoration, reduced oxidative stress, oxidative DNA damage, inflammation, insulin resistance, and endothelial dysfunction, whereas mitochondrial function, body composition (including less fat mass), muscle strength, exercise capacity, and cognition were improved.

In 2022, similar data was published by the same research group (Kumar et al.). In that study, glycine + NAC (again using 100 mg each for glycine and NAC/kg body weight) supplementation in 61-80yr olds (n=11) for 16-weeks improved the same markers that were published in 2021, and impacted others, including improved markers of cell senescence, stem cells, mitophagy, blood pressure, waist size, and gait speed.

When considering the data from these 2 RCTs, GSH restoration may be a promising approach for improving health-related outcomes in GSH-deficient in older adults.

But, that’s not the purpose of this post. Can GSH restoration increase lifespan? Also, do centenarians (people older than 100y) have relatively higher or lower levels of GSH in blood?

First, glycine + NAC (GlyNAC) supplementation extends lifespan (in mice; Kumar et al. 2022). In that study, there were 2 groups of C57BL/6J mice, which were fed a either regular diet (no GlyNAC; 8 males, 8 females), or the regular diet supplemented with GlyNAC (8 males, 8 females), with amounts that were similar to that used in the 2 human RCTs. Supplementation started at 65 weeks of age (equivalent to starting ~40y in people), and when comparing 50% survival, which is the time when half the colony was dead and half was still alive, GlyNAC-supplemented mice had a 24% increased median survival, when compared with control-fed mice.

However, this study had some limitations. 16 mice per group is relatively small for lifespan studies-for example, see my 2 recent CR, fasting, and/or circadian alignment videos, where > 40 mice per group were used to evaluate lifespan. Additionally, no info was published about food consumption or body weight, which is important because if GlyNAC-supplemented mice ate less food than controls, that can explain the lifespan-extending effect. Mild calorie restriction (5%) can impact lifespan, so omission of food intake or body weight is potentially important.

In contrast, this study had strengths, including measuring GSH levels is several tissues-heart, liver and kidney. In those organs, there was a clear, age-related decline for GSH, but, aged mice that were supplemented with GlyNAC had significantly higher GSH when compared with unsupplemented controls. From this we can conclude that the lifespan-extending effect of GlyNAC supplementation is associated with GSH restoration in multiple tissues.

What about the data in centenarians? Earlier, we saw that GSH levels decline during aging, so is it reasonable to expect further declines in people that are 100yrs old (or older)?

In contrast, blood GSH levels were 48% higher in close-to-centenarians (average age, 97y, n=116) when compared with their offspring (average age, 67y, n=232; Xu et al. 2022). Collectively, when considering these data, the 2 human RCTs, and the mouse lifespan study, it suggests that relatively higher levels of GSH may be an important part of a pro-longevity strategy. Interestingly, each of GSH’s component amino acids were also significantly higher in the 97-yr olds, and likely explain the higher levels of GSH found in the centenarians of the Xu study.

In video format:

https://www.youtube.com/watch?v=i_w_DYKvlBM&t=1s

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References:

Inal et al: Age-related changes in the glutathione redox system https://pubmed.ncbi.nlm.nih.gov/11835271/

Kumar et al 2021:Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial https://pubmed.ncbi.nlm.nih.gov/33783984/

Kumar et al 2022: Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial https://pubmed.ncbi.nlm.nih.gov/35975308/

Kumar et al 2022: GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage https://pubmed.ncbi.nlm.nih.gov/35268089/

Nguyen et al: Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione https://pubmed.ncbi.nlm.nih.gov/23534396/

Qui-lin et al: Age-related changes of the redox state of glutathione in plasma https://pubmed.ncbi.nlm.nih.gov/16232335/

Sekhar et al: Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation https://pubmed.ncbi.nlm.nih.gov/21795440/

Xu et al: Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors https://www.nature.com/articles/s43587-022-00193-0

Yang et al: Effect of ageing on human plasma glutathione concentrations as determined by high-performance liquid chromatography with fluorimetric detection https://pubmed.ncbi.nlm.nih.gov/8749248/

Glycine + N-Acetyl Cysteine Supplementation Increases Lifespan

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Paper referenced in the video:
Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial
https://pubmed.ncbi.nlm.nih.gov/35975308/

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in
Mice Increases Length of Life by Correcting Glutathione
Deficiency, Oxidative Stress, Mitochondrial Dysfunction,
Abnormalities in Mitophagy and Nutrient Sensing,
and Genomic Damage
https://pubmed.ncbi.nlm.nih.gov/35268089/

Glycine and N-acetylcysteine (GlyNAC) supplementation in
older adults improves glutathione deficiency, oxidative
stress, mitochondrial dysfunction, inflammation, insulin
resistance, endothelial dysfunction, genotoxicity, muscle
strength, and cognition: Results of a pilot clinical trial
https://pubmed.ncbi.nlm.nih.gov/33783984/

Fasting Without Calorie Restriction Extends Lifespan

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Paper referenced in the video:
Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories
https://pubmed.ncbi.nlm.nih.gov/30197301/