CR III Conference talk summary
Summary by Dean Pommerleau

Talk 15: Scientific Panel - Fontana, Masoro, Mattson, Horwitz, Johnson

Q: How low can you go (calorie-wise)?

Mattson: BMI crude estimate. Below 18.5 or 18 may be bad.

Masoro: There is a risk to CR. Rodent data says early life mortality higher in CRed group.

Q: Will primate studies show lifespan extension?

Masoro: Concerned that primate studies are "poking and prodding" monkeys too much, which may taint results. Need tighter controls.

CR animals do better at handling minor stress like heat and minor surgery

CR animals do worse at dealing with cold stress - don't have the necessary fuel reserves.

Wound healing better w/ CR if you give more food shortly before or at time of wound.

Mattson: "perturbing" animals (poking and prodding) may be more like real life, so data may be more reflective of real effect.

Q: What about intermittent fasting + CR?

Mattson: Don't have data. Rats clearly are CRed on EOD feeding (~30% CR) - confound results. Some strains of mice don't lose weight on EOD feeding.

Johnson: People generally don't quite eat twice as many calories on the "On-day" - so it is naturally a combination of intermittent feeding and CR

Q: What about vitamin supplements?

Johnson: Doesn't see data to support supplements.

Fontana: Vitamin D important, but best to get from sun. Nearly all CRers taking supplements in his study. Almost none of Raw food people do?

Q: Please describe practice of CR or not.

Mattson: Vegetarian + fish + yogurt. Lots of whole grains. BMI 18-18.5. 1/2 hour exercise / day rigorous. A bit anemic. 2000-2200K per day.

Masoro: Has never practiced CR. At age 69 he was diagnosed w/ severe heart disease. Instructed to do exercise and clean up diet. Now does low fat. Mostly fish and vegetables ad lib.

Fontana: Healthy diet all his life. Always thin. Formerly macro-biotic, lots of grains, legumes, fish. Very rare to eat other meats. Never eats desserts or sweets. Lots of veggies. Doesn't count calories. BMI 20.2. Exercise a lot. Yoga + resistance + biking. Doesn't supplement - gets micronutrients from foods.

Q: Where will we be in 5 years in our understanding of primary aging?

Masoro: Feels we already know the nature of aging. Doesn't buy primary / secondary aging distinction. Aging relates to fact that damage is inevitable. Free radicals aren't only bad guy. The extent to which we age is determined by our ability to repair, and cope w/ the slings and arrows that come at us.

Mattson: We don't know all the details of aging at molecular level, and we'll continue to make progress. Masoro agrees - lots of details left to be worked out. Thinks further research into pathways involved in oxidative metabolism, insulin-signalling etc. will bear fruit - showing us details of mechanisms of aging.

Not optimistic about recommendations that people adopt dietary changes. But also not very optimistic about narrowly targeted mimetics (like sirtuins). Thinks that if a mimetic is going to be effective, it must mimic CR at early stage in its effects pathway - e.g. appetite suppression or blocking absorption. Otherwise, the mimetic won't cover all the multitude of ways that our body gets damaged as we age. Something else will eventually get us.

Q: Is hormesis relevant in yeast?

Masoro: Yes. Definitely. Sinclair's work can be interpreted as a demonstration of hormesis for extension of lifespan in yeast. Hormesis pathway in different organisms may be different (rats vs. yeast). Sirtuins may be shared, but can't expect all pathways to be identical between organisms.

Q: How does assay for Sirtuins work?

Horwitz: Described detailed biochemical technique for measuring sirtuin levels.

Q: Resveratrol sounds like fountain of youth. Can it be the "magic bullet"?

Everyone agreed resveratrol has almost ZERO probably of being THE magic bullet.

General agreement - save money, eat varied diet.

Mattson: Save your money (don't buy supplements).

Horowitz: Resveratrol probably fairly harmless - non-toxic. So it won't hurt you. But benefits uncertain. But Sinclair and other researchers are taking it. But of course they are getting it from sponsor for free...

Q: Please share view of exercise. Is CR only better for longevity?

Fontana: If overweight - exercise beneficial.

Johnson: Excessive exercise causes more free radical damage.

Q: what about resistance training?

Fontana: Resistance training helpful for maintaining muscle mass. Doesn't burn as many calories as aerobic exercise. Matter of balance. Don't build big muscles, but don't let too much muscle atrophy on CR or with age.

Q: BMR. Is being a "burner" good or bad?

Masoro: Rate of living theory has been thorough discredited. Aging much more complicated than just how many calories you're burning.

Q: Mortality doubling rate reduced by CR in rats. Clear indicator of intrinsic mortality slowing?

Masoro: In a population of (rodents), yes. This shows CR slows intrinsic aging. But we want marker of aging for individual. We still haven't been able to find good biomarker of aging.

Fontana: CR may lengthen life, but may also increase risk of dying. The average lifespan of a CR'ed population of humans may be longer, but an individual may be hurt by CR if taken to "extreme". Unfortunately we don't have a good way to judge how far is too far. In general, may be better to be in "safer" range for body fat, BMI, etc.