FASTING MIMICKING DIET

DIETARY INTERVENTIONS

Calorie restricti

on

reducing calories 30-

40%

Dietary restricti

on

reducing macro-nutri-ents with or without re-

ducing calo-ries

Fasting

Intermittent or prolonged

Fontana L1, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010 Apr 16;328(5976):321-6.

CR IN MONKEYS HAS INCONSISTENT EFFECTS ON LONGEVITY

According to 2 existing studies

Colman RJ et al. Caloric restriction delays

disease onset and mortality in rhesus

monkeys. Science. 2009 Jul 10; 325(5937):201-4.

Mattison JA et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012

Sep 13;489(7415):318-21.

WHY SUCH A DIFFERENCE?

NIA study WNPRC study

Calorie intake17.3% from

protein, 5% from fat

15% from protein, 10%

from fat

Protein sourceCorn, wheat, soybean, fish, alfalfa meal

Lactalbumin

Source of carbsGround wheat,

corn, 3.9% sucrose

Corn, starch, 28.5% sucrose

Feeding regime Not ad libitum True ad libitum

IS THERE AN IDEAL RATIO?

RESTRICTING AMINO ACIDS EXTENDS

LONGEVITYYEAST: methionine (Met) restriction more than doubles lifespan; lack of serine (Ser), threonine (Thr), and valine (Val) extends lifespan and improved DNA repair

WORMS: lack of purified diets, eat-2 mutant lives longer in part because of reduced TOR and S6 kinase activity

FLIES: methionine restriction extends lifespan, carbohydrate to protein ratio plays a bigger role than just calorie intake

RODENTS: methionine and tryptophan restriction extend lifespan, protein restriction reduces spontaneous tumor formation, decreases mitochondrial reactive oxygen species, serum glucose, insulin, and IGF-I levels, improves hair growth

mTOR signaling pathway

HUMANS• Humans: analysis of 6,381 US men and women

aged 50 and above from NHANES III cohort showed reduction of cancer and all-cause risk mortality in people aged 50-65, but not in >65.

Levine ME et al, Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population.

Cell Metab. 2014 Mar 4;19(3):407-17.

HUMANSNurses’ Health Study (85 168 women, 26 years) and Health Professionals’ Follow-up Study (44 548 men, 20 years) macronutrients in diet were scored

When intake mostly from ANIMAL-BASED PRODUCTS — the lowest carbs intake = higher all-cause mortality

VEGETABLE-BASED low carb regimen = lower all-cause and cardiovascular disease mortality

HIGHER PLANT-BASED PROTEIN intake correlates with lower ischemic heart disease and strokes (Health Professionals’ Follow-up Study)

Increase in ischemic heart disease correlated with high RED MEAT and high fat DAIRY INTAKE (Nurses’ Health Study)

Ecuadorean dwarfs deficient in growth hormone and IGF-1 don’t develop cancer or

diabetes

CENTENARIANS

SICILY – Mediterranean diet - three small meals comprised of small amounts of carbohydrates and meat and large amounts of seasonal fruits and vegetables, beans, olives, and olive oil

OKINAWA – diet rich in vegetables, fruits, and grains, only 9% of calories coming from proteins, mostly plant-based

Intermittent fasting extends longevity

MICE• 16 months age, 4 days twice a month• 11% median lifespan extension, no

effect on maximum lifespan• Decreases in visceral fat, glucose,

and IGF-1 levels• Improved femoral bone density, liver

regeneration, learning, memory and neurogenesis

Brandhorst S. et al., A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015 Jul 7;22(1):86-99.

HUMANS• 38 individuals, 19.8–67.6 years for the

control cohort and 27.6–70 years for the FMD cohort

• 5 days every month for 3 months• 9%–10% proteins, 34%–47% carbohydrates,

and 44%–56% • Blood glucose reduced by 11%, ketone

bodies increased 3.7-fold, Circulating IGF-1 was reduced by 24% by the end of the FMD period and remained 15% lower after resuming the normal diet, IGFBP-1 was increased 1.5-fold, 3% reduction in body weight, CRP levels were reduced

LONGEVITY COOKBOOK CHAPTERS

1. Longevity research1. Fundamental mechanisms of aging2. Longevity genetic engineering3. Cell therapy, cloning and tissue engineering4. Aging, inflammation, immune response5. Microbiome6. Geroprotectors

2. Diet and longevity1. Clinical trials of food2. Bioinformatic analysis of the nutrients3. Personalized nutrition4. Growing food with given properties5. Fasting mimicking diet

LONGEVITY COOKBOOK CHAPTERS

3. Lifestyle and longevity 1. Biorhythms, sleep and nutrition regimes2. Phycology of life extension3. Health markers

4. Social efforts for longevity1. How do you act on the stock exchange in favor of longevity?2. Social changes in favor of longevity