Tag Archives: centenarian

Lithocholic Acid: A Gut Bacterial Metabolite That Extends Lifespan

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Papers referenced in the video:
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

Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism https://pubmed.ncbi.nlm.nih.gov/30157432/

Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production https://pubmed.ncbi.nlm.nih.gov/11371619/

Alterations in xenobiotic metabolism in the long-lived Little mice https://pubmed.ncbi.nlm.nih.gov/17521389/

Bile Acids: A Communication Channel in the Gut-Brain Axis https://pubmed.ncbi.nlm.nih.gov/33085065/

Lithocholic acid significantly improves the survival of Drosophila melanogaster https://pubmed.ncbi.nlm.nih.gov/30051966/

Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians https://pubmed.ncbi.nlm.nih.gov/34325466/

Divergent effects of resistance and endurance exercise on plasma bile acids, FGF19, and FGF21 in humans https://pubmed.ncbi.nlm.nih.gov/30089729/

Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes https://pubmed.ncbi.nlm.nih.gov/20622262/

Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians https://pubmed.ncbi.nlm.nih.gov/34325466/

Centenarian Blood Test Analysis (n=1,754)

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Papers referenced in the video:

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

Association between fasting glucose and all-cause mortality according to sex and age: a prospective cohort study https://pubmed.ncbi.nlm.nih.gov/28811570/

Predicting age by mining electronic medical records with deep learning characterizes differences between chronological and physiological age https://pubmed.ncbi.nlm.nih.gov/29113935/

Age and sex variation in serum albumin concentration: an observational study https://pubmed.ncbi.nlm.nih.gov/26071488/

Commonly used clinical chemistry tests as mortality predictors: Results from two large cohort studies https://pubmed.ncbi.nlm.nih.gov/33152050/

The gamma gap predicts 4-year all-cause mortality among nonagenarians and centenarians https://pubmed.ncbi.nlm.nih.gov/29348636/

Triglyceride centenarian studies are referenced in this post from my website: https://michaellustgarten.com/2020/02/19/blood-testing-whats-an-optimal-value-for-triglycerides-2/

Effects of blood triglycerides on cardiovascular and all-cause mortality: a systematic review and meta-analysis of 61 prospective studies https://pubmed.ncbi.nlm.nih.gov/24164719/

High-density lipoprotein cholesterol and all-cause mortality by sex and age: a prospective cohort study among 15.8 million adults https://pubmed.ncbi.nlm.nih.gov/33313654/

Insulin Sensitivity Is A Hallmark Of Longevity

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HOMA calculator: https://www.omnicalculator.com/health…

Papers referenced in the video:

Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice https://pubmed.ncbi.nlm.nih.gov/24175…

Glucose regulation and oxidative stress in healthy centenarians https://pubmed.ncbi.nlm.nih.gov/12543…

Distribution of blood glucose and prevalence of diabetes among centenarians and oldest-old in China: based on the China Hainan Centenarian Cohort Study and China Hainan Oldest-old Cohort Study https://pubmed.ncbi.nlm.nih.gov/32643…

Prevalence and Ethnic Pattern of Diabetes and Prediabetesin China in 2013 https://pubmed.ncbi.nlm.nih.gov/28655…

Families enriched for exceptional longevity also have increased health-span: findings from the long life family study https://pubmed.ncbi.nlm.nih.gov/24350…

High FGF21, Low Insulin And Glucose: A Pro-Longevity Strategy?

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Papers referenced in the video:

FGF21 and Chronic Kidney Disease: https://www.sciencedirect.com/science…

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice: https://www.ncbi.nlm.nih.gov/pmc/arti…

Inhibition of growth hormone signaling by the fasting-induced hormone FGF21: https://pubmed.ncbi.nlm.nih.gov/18585…

Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice: https://pubmed.ncbi.nlm.nih.gov/32877…

Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression: https://pubmed.ncbi.nlm.nih.gov/31773…

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice: https://www.ncbi.nlm.nih.gov/pmc/arti…

Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses: https://pubmed.ncbi.nlm.nih.gov/28552…

Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer’s disease in comparison with healthy aging: https://pubmed.ncbi.nlm.nih.gov/33131…

Aging is associated with increased FGF21 levels but unaltered FGF21 responsiveness in adipose tissue: https://pubmed.ncbi.nlm.nih.gov/30043…

Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals: https://pubmed.ncbi.nlm.nih.gov/26042…

Lower All-Cause, Cardiovascular, and Cancer Mortality in Centenarians’ Offspring: https://pubmed.ncbi.nlm.nih.gov/15571…

Favorable Glucose Tolerance and Lower Prevalence of Metabolic Syndrome in Offspring without Diabetes Mellitus of Nonagenarian Siblings: The Leiden Longevity Study: https://pubmed.ncbi.nlm.nih.gov/20398…

Carotenoids Are Associated With A Younger Epigenetic Age And Reduced All-Cause Mortality Risk

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Papers referenced in the video: DNA methylation

GrimAge strongly predicts lifespan and healthspan:

https://pubmed.ncbi.nlm.nih.gov/30669…​

GrimAge outperforms other epigenetic clocks in the prediction of age-related clinical phenotypes and all-cause mortality:

https://pubmed.ncbi.nlm.nih.gov/33211…​

Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies: https://pubmed.ncbi.nlm.nih.gov/30475…​

Albumin is included as a biological age predictor:

https://www.ncbi.nlm.nih.gov/pmc/arti…​

https://www.ncbi.nlm.nih.gov/pmc/arti…​

https://www.ncbi.nlm.nih.gov/pmc/arti…​

https://pubmed.ncbi.nlm.nih.gov/30993…​

Age-related change data for albumin:

https://pubmed.ncbi.nlm.nih.gov/26071…​

Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages: https://www.nature.com/articles/s4146…

HDL: What’s Optimal For Minimizing Disease Risk And Maximizing Longevity?

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Meta-analysis for the association between HDL with all-cause mortality risk has identified HDL levels 55 – 60 mg/dL range as optimal. However, that data includes subjects up to 85y-in the video, I present data for 85y – 115yr olds that additionally suggests HDL in the 55 – 60 mg/dL range as optimal. In addition, I show my own HDL data over the past 15 years (n=34), the correlation for HDL with my diet, and how I plan on consistently increasing my 15-year average HDL of ~44 mg/dL to the 50’s.

Blood Testing: What’s Optimal For Triglycerides?

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In terms of all-cause mortality risk, is the reference range for circulating triglycerides (TG, <150 mg/dL) optimal?

A meta-analysis of 38 studies in 360,556 subjects with a median age of 48y and a 12-year follow-up reported lowest all-cause mortality risk for subjects with TG values less than 90 mg/dL (equivalent to ~1 mmol; Liu et al. 2013). As shown below, each successive 90 mg/dL increase was associated with a 12% higher all-cause mortality risk. A person with a value closer to the high end of the reference range, ~150 would have a ~7% increased mortality risk compared someone with a value ~90. In other words, there would be 7 more deaths per 100 total people at a TG value of 150, compared with the death rate for people with values less than 90.

tg mortal

Added importance for the association between TG values less than 90 with all-cause mortality risk come from studies of people who have lived longer than 100 years, centenarians. As shown below, triglyceride values less than 101 mg/dL have been reported in 9 of 11 centenarian studies:

tg mort

What’s my TG value? As shown below, I’ve measured triglycerides 23 times since 2015, with an average value of 52 mg/dL:tg 2020

With the goal of keeping triglyceride levels low, are there dietary factors that influence it? When compared with my dietary data, the strongest correlation (r = 0.73, R2=0.5339) is present for triglycerides with my calorie intake. In other words, a higher daily calorie intake is associated with higher levels of triglycerides:

tg vs cals 2020

Based on this correlation, should my triglycerides start to rise in the future, a first step would be reducing my average daily calorie intake, which since October 2019 has been ~2550 calories/day.

 

If you’re interested, please have a look at my book!

References

Liu J, Zeng FF, Liu ZM, Zhang CX, Ling WH, Chen YM. Effects of blood triglycerides on cardiovascular and all-cause mortality: a systematic review and meta-analysis of 61 prospective studies. Lipids Health Dis. 2013 Oct 29;12:159.