Tag Archives: calorie restriction

Fasting Drives The Geroprotective Effects Of A Calorie-Restricted Diet

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Paper referenced in the video:

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice https://www.nature.com/articles/s42255-021-00466-9

Insulin Sensitivity Is A Hallmark Of Longevity

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…

SIRT6 Positively Affects The Hallmarks Of Aging And Extends Lifespan

Papers referenced in the video:

Sirtuins, Healthspan, and Longevity in Mammals https://www.sciencedirect.com/science…

Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH https://pubmed.ncbi.nlm.nih.gov/24011…

Resveratrol improves health and survival of mice on a high-calorie diet https://pubmed.ncbi.nlm.nih.gov/17086…

Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice https://pubmed.ncbi.nlm.nih.gov/20974…

Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer https://www.nature.com/articles/ncomm…

Restoration of energy homeostasis by SIRT6 extends healthy lifespan https://pubmed.ncbi.nlm.nih.gov/34050…

The sirtuin SIRT6 regulates lifespan in male mice https://pubmed.ncbi.nlm.nih.gov/22367…

SIRT6 in Senescence and Aging-Related Cardiovascular Diseases https://pubmed.ncbi.nlm.nih.gov/33855…

Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling https://pubmed.ncbi.nlm.nih.gov/26940…

Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6 https://pubmed.ncbi.nlm.nih.gov/27101…

A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer’s Disease, Aging, Cancer, Inflammation, and Diabetes https://pubmed.ncbi.nlm.nih.gov/33920…

Acute Exercise Leads to Regulation of Telomere Associated Genes and MicroR A Expression in Immune Cells https://pubmed.ncbi.nlm.nih.gov/24752…

The effect of 12-week resistance exercise training on serum levels of cellular aging process parameters in elderly men https://pubmed.ncbi.nlm.nih.gov/32919…

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

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…

Blood Test #6 In 2020: What’s My Biological Age?

Discussed in the video:

What’s my biological age on blood test #6 in 2020?

What’s my average biological age for 2020, and how does it compare with 2019?

Are there links between calorie intake, cardiovascular fitness (RHR, HRV), and diet composition with my biological age?

CD38 Gets In The Way Of NR And NMN For Increasing NAD+

NR and NMN are popular ways to try to boost levels of NAD+, but that approach hasn’t worked every time in human studies. One reason for that may involve CD38, which degrades both NR and NMN. With the goal of boosting NAD+ levels during aging, why does CD38 increase with age, and what can be done about it? All that and more in this video!

Optimizing Biological Age: White Blood Cells

Circulating levels of white blood cells (WBCs) are one of the 10 variables used to quantify biological age with PhenoAge (https://atomic-temporary-71218033.wpcomstaging.com/2019/09/09/quantifying-biological-age). The reference range for WBCs is 4.5 – 11 *10^9 cells/L, but within that range, what’s optimal?

Several studies have reported that WBCs greater than 5 are associated with an increased all-cause mortality risk (Ahmadi-Abhari et al. 2013, Samet et al. 2005, Weijenberg et al. 1996). While observational studies are important for identifying associations with mortality risk, stronger evidence is obtained when the data from the same subjects are tracked for a long time period. Perhaps the best evidence for the association between WBCs with mortality risk comes from the Baltimore Longitudinal Study on Aging (BLSA), which studied 2803 men and women over a period of 44 years (Ruggiero et al. 2007). As shown below, subjects that had circulating WBCs between 3.5 – 6 had the best survival, whereas WBCs below 3.5, between 6 – 10, and 10+ each had successively higher risk. The 0.5 point on the y-axis of the curve (survival) is defined as 50% mortality, and is the point where half of the study subjects died, whereas the remaining 50% were still alive. At that point, compared with subjects that had WBCs between 6 – 10, people that had WBCs between 3.5 – 6 lived ~7 years longer! So getting your WBC into that range may be a big deal for increasing life expectancy.

wbc ferr

How can you reduce circulating WBCs? One way to reduce WBCs is to eat less calories, thereby reducing your body weight. As shown below, eating less calories resulted in a decreased BMI and decreased WBCs in the Biosphere II project (Walford et al. 2002), almost exactly in the same pattern:

cr bmi

WBC Biosphere

Because calorie restriction reduced WBCs from ~6.8 to 4.6, should 4.6 be considered optimal? In support of this idea, calorie restriction is well documented to increase lifespan in a variety of organisms, including flies, worms, and rodents. Although there isn’t any evidence (yet) on the long-term effects of calorie restriction (CR) on lifespan in people, it has been shown to be protective against age-related diseases, including abdominal obesity, diabetes, hypertension, and cardiovascular disease (Omodei and Fontana 2011). Therefore, a reduced WBC level may be related to the positive health-related effects of CR. 

As an argument against using the CR-mediated reduction in WBC as a guide for what the optimal range should be, calorically-restricted mice have a decreased survival in response to infection (Goldberg et al. 2015):

cr survival

However, it’s important to note that infection-related survival was decreased in CR mice that were 40% restricted in terms of daily calories. Based on the Biosphere 2 data above, BMI was reduced from ~23 to 19, which translates into a 17% reduction. However, whether 17% CR is better for improving infection-related survival compared with 40% CR is currently unknown.

What’s my WBC level? Shown below is my WBC data for the past 16 years, including 25 measurements (average WBCs, 4.78 * 10^9 cells/L). The 2 red lines delineate the 3.5 – 6 range that was associated with an increased lifespan in the BLSA study (Ruggiero et al. 2007), and based on that, I’ve only had 1 measurement that was higher than that range.

wbc update

Starting from the red arrow below, WBCs increase during the 22-year period that precedes death (Ruggiero et al. 2007), so making sure that they don’t go up during aging is important!

wbc age

 

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

 

References

Ahmadi-Abhari S, Luben RN, Wareham NJ, Khaw KT. Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive proteinfibrinogen and leukocyte count in men and women: the EPIC-Norfolk studyEur J Epidemiol. 2013 Jul;28(7):541-50.

Goldberg EL, Romero-Aleshire MJ, Renkema KR, Ventevogel MS, Chew WM, Uhrlaub JL, Smithey MJ, Limesand KH, Sempowski GD, Brooks HL, Nikolich-Žugich J. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. Aging Cell. 2015 Feb;14(1):130-8.

Jee SH, Park JY, Kim HS, Lee TY, Samet JM. White blood cell count and risk for all-causecardiovascular, and cancer mortality in a cohort of KoreansAm J Epidemiol. 2005 Dec 1;162(11):1062-9.

Omodei D, Fontana L. Calorie restriction and prevention of age-associated chronic diseaseFEBS Lett. 2011 Jun 6;585(11):1537-42.

Ruggiero C, Metter EJ, Cherubini A, Maggio M, Sen R, Najjar SS, Windham GB, Ble A, Senin U, Ferrucci L. White blood cell count and mortality in the Baltimore Longitudinal Study of AgingJ Am Coll Cardiol. 2007 May 8;49(18):1841-50.

Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci. 2002 Jun;57(6):B211-24.

Weijenberg MP, Feskens EJ, Kromhout D. White blood cell count and the risk of coronary heart disease and all-cause mortality in elderly menArterioscler Thromb Vasc Biol. 1996 Apr;16(4):499-503.

Optimizing Biological Age: Is Calorie Restriction Essential?

My goal is to break the world record for lifespan, 122 years, which is currently held by Jean Calment. How do I plan to do that? A good start would be calorie restriction (CR), a diet where you eat 10-30%+ less calories than your normal intake. CR is the gold standard for increasing lifespan in a variety of organisms, including yeast, flies, worms, and rodents (McDonald et al. 2010).

With the goal of maximizing my health and lifespan, in April 2015, I started a CR diet. Inherent in that was weighing all my food and recording it on an online website that tracks macro-and micro-nutrients. From then until March 2016, I was pretty good at keeping my calories relatively low, as I averaged 2302 calories. However, since 3/2016, it’s been exceedingly difficult to keep my calories that low, as I’ve averaged 2557 calories/day. So is having a higher calorie intake worse for my lifespan goal than a lower calorie intake?

Maybe not. In addition to tracking my daily nutrition since 2015, I’ve also had regular blood testing performed. I’ve measured the typical things that you get at a yearly checkup, including the lipid profile (triglycerides, total cholesterol, LDL, HDL, VLDL) markers of kidney and liver  function (BUN, creatinine, uric acid, and ALT, AST, respectively), and the complete blood count (red and white blood cells, and their differentials). By tracking my daily nutrition and circulating biomarkers, I’m able to quickly intervene on any potential aging and disease-related mechanisms by using my diet to optimize my circulating biomarkers.

On my quest for optimal health and lifespan, biological age is more important than my chronological age (I’m 46y). So what’s my biological age? Between 2016-2019, the group at Insilico Medicine published 2 papers that included circulating biomarker data from more than 200,000 people (Putin et al. 2015, Mamoshina et al. 2018) to derive a biological age predictor (aging.ai). So what’s my biological age?

Shown below is my predicted biological age over 13 blood tests from 3/2016 to 6/2019:

agingai2

Although I wasn’t on a CR diet during that time, my average biological age was 29.2 years, which is ~34% younger than my chronological age. Would my biological age be even younger with a lower calorie intake? I’m working on reducing my calorie intake again (it’s not easy for me), so stay tuned for that!

Here are the my biomarker values corresponding to each blood test, for anyone who wants to double check the results:
agingai2 values

References

Mamoshina P, Kochetov K, Putin E, Cortese F, Aliper A, Lee WS, Ahn SM, Uhn L, Skjodt N, Kovalchuk O, Scheibye-Knudsen M, Zhavoronkov A. Population specific biomarkers of human aging: a big data study using South Korean, Canadian and Eastern European patient populations. J Gerontol A Biol Sci Med Sci. 2018 Jan 11.

McDonald RB, Ramsey JJ. Honoring Clive McCay and 75 years of calorie restriction research. J Nutr. 2010 Jul;140(7):1205-10.

Putin E, Mamoshina P, Aliper A, Korzinkin M, Moskalev A, Kolosov A, Ostrovskiy A, Cantor C, Vijg J, Zhavoronkov A. Deep biomarkers of human aging: Application of deep neural networks to biomarker development. Aging (Albany NY). 2016 May;8(5):1021-33.

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