CR III Conference talk summary
Summary by Dean Pommerleau

Speaker 14: Luigi Fontana: Energy Intake, Food Consumption and Aging in Humans

As an MD, Luigi interested in prevention, rather than treatment of disease.

Luigi's definition of Longevity: Remain physically, emotionally and spiritually healthy and happy for as long as possible.

Showed some data showing increased mortality among very thin. Could be smoking and undiagnosed cancer.

But the other extreme, obesity, and particularly abdominal obesity (visceral fat) is very bad for health/longevity.

Luigi did liposuction study on obese women to understand if surgical removal of a lot of fat (20% of body weight), without changing food intake. No difference in insulin sensitivity after surgery. Very little changed in fact, except leptin.

Conclusion: is isn't just the presence of fat. Another valid hypothesis though - it is the visceral fat that makes the difference, not the subcutaneous (which gets removed in liposuction).

Date from Human CR Study (CALERIE): One woman in study has lost LOTS of visceral, but relatively little subcutaneous fat. She is no longer diabetic, cholesterol improved, inflammation markers went down. She was not atypical.n

But some parameters haven't changed in CALERIE study like Luigi has observed in us long-term CRer. Why not? Diet composition? Duration of CR? Extreme degree of CR or weight loss?

Now on to stuff on study Luigi is conducting on us CR practitioners, along with three others groups:

Four groups:

  • Low energy intake - (CR) (1671kcal/day) - relatively high protein, moderate fat
  • Higher energy intake/exped. (EX) - Exercise (2900kcal/day) - 50mi running/wk
  • Control (2300kcal/day) (C) - SAD diet
  • Raw food people (2050kcal/day) - high fat, low protein (RAW)
CRers has higher VO2Max than controls, but less than exercisers.

Study results - differences between four groups. '=' or '<=' represents non-significant difference, '<<' represents very big and significant difference.

CV Risk factors:

  • VO2Max: C < Raw = CR < Ex
  • BMI: Raw = CR < EX < C
  • Body Fat: CR < EX < Raw < C
  • Trunk Fat: CR < RAW = EX < C
  • Leptin: C <= EX <= Raw << C
  • Apidonectin: C <= raw <= EX < CR
  • Systolic BP: CR = RAW < EX = C
  • Diastolic BP: CR = RAW < EX < C
  • Max HR: C < CR = EX
BP looks much more important for CV. Above 115/75 appears to increase risk of CV. Interesting: High BP not prevented by exercise.

Cholesterol is partly a result of genetics, but largely diet/lifestyle related.

  • Total Chol: Raw < CR = EX < C
  • LDLc: Raw <= CR <= EX < C
  • HDLc: C < Raw = CR = EX
  • Trig: Raw = CR = EX << C
  • Tg/HDLc: Raw = CR = EX << C
Historical data from CRers show majority of lipids improvements by 1 year on CR.
  • Fasting glucose: CR <= Raw < EX < C
  • Insulin: CR <= Ex <= Raw << C
  • IR resistance: CR <= Ex <= Raw << C
  • CRP: CR <= Raw <= Ex < C
  • Artery wall thickness: CR <= Raw < EX <= C

Does CR delay aging in humans?

Can't claim that yet. But it does dramatically increase life expectancy - based on improvements in risk factors, particularly for CVD.

Potential Markers of primary aging:

  • Growth factors: Insulin, IGF-1, etc.
  • BP and artery stiffness
  • Inflammation markers: CRP, TNF-a, IL-6
  • Body Temp, RMR, hormones (T3/rT3)
  • White blood cell and lymphocyte count
  • Markers of oxidative stress and protein glycation
  • Heart, kidney and lung function markers
Unpublished data: CR hearts look 15-20 years younger than heart (based on measure of ventricular filling).
  • IGF-1: Raw << CR = Ex <= C
Interesting: CRers IGF-1 wasn't significantly different from controls.
  • s-PDGF-AB (important growth factor): CR < Raw = EX <= C
  • s-TGF-Beta1 (another growth factor): CR < Raw <= Ex = C
CRers show little change in IGF-1, but much lower IGF-1 receptors, meaning our non-significant reduction in IGF-1 may not be the whole story wrt to IGF-1.
  • WBC: CR <= Raw < EX < C
  • Same relationships for lymphocytes, etc.
WBC could be marker of CR and aging. Spleen shrunk by CR - where WBC are generated.

Paradoxically - CR -> improved immune function accompanied by lower WBC (lymphopenia).

  • Anion GAP: CR < Raw <= Ex <= C
  • Total CO2: CR > Raw = ex > C
  • Urine PH : CR = raw > EX = C
Achilles heal of CR? - bone mass
  • Lumbar BMD: Raw <= CR < Ex <= C
  • Same for other bone sites
What about bone quality? Possibly bone quality higher in CR?
  • Bone turnover not higher in CR people - which is good
  • Vit D: Raw >= CR > EX >= C
  • Cortisol: CR >= C = EX = RAW

Conclusions:

  • CR, raw and ex have markedly reduced risk of CVD
  • CR and raw have powerful anti-inflammatory risk
  • CR and raw have lower bone mass
  • Don't have good markers of cancer or aging - so can't comment
Bone Health comment: Luigi thinks low BMD in the presence of low inflammation may not be nearly as negative as low BMD w/ high inflammation. He's going to look at measures of bone architecture in next round of tests on these subjects.

Investigating cell proliferation and apoptosis - but difficult work to do. No data to report yet.

Luigi thinks CR + moderate exercise better than CR alone.

Whether CR slows aging depends on your definition of aging.

Planning to do double labeled water experiments to measure calorie expenditure in next round of tests of his subjects.

Hoping to do gene expression tests in next round as well.

Doing protieomics tests on subject's serum to measure differences in proteins.

No good markers of pushing CR too far but his gut tells him pushing too far is dangerous. Once your BP or your WBC gets down to a certain (lower) level, you get nearly all the benefits. Pushing further increases other risks, and provides little benefit.