Weindruch - Historical Perspective on Calorie Restriction and Aging
-------------------------------------------------------------

CR topics being studied:
.       Mechanisms in rodents
.       Efficacy in primates
.       CR mimetics

95% of CR rodent studies have been in early onset CR.

Mice diet most often of cancer.

McCay - First to publish study to show CR extends lifespan, 1935.

He's currently focused on gene chip - what metabolic change is occurring in
CR that could explain effects on aging?

He feeds rats ~20% less than they would eat ad lib - leads to non-obese,
healthy older mice.

Max lifespan he report - Average age of death of 10% longest live of group.

Old CR animals autopsies - hard to tell why they die. The usual diseases he
sees in dead mice (e.g. cancer) he rarely sees in CR animals. They just seem
to dry.

Candidate CR Mechanisms:
.       lower oxidative stress damage
o       lower ROS generation, increased removal, increased repair
.       lower of glycation/glycoxidation
.       lower glycation/glycoxidatio
.       Lower body temp
.       Better DNA protection and/or repair
.       Neuroendocrine changes

Seems like evidence that increased antioxidant not present in CR - may
actually be lower, particularly for exogenous AO's (e.g. antioxidant
vitamins).

Latest thoughts - Free radicals influence cellular function, gene
expression, etc., which he thinks may be very important.

Non-human primates: NIA studies started in late 80's. Longevity effects not
clear until around 2020.

Human primates: No direct, but some. Vallejo nursing home study,
biospherians, Okinawans. Growing evidence CR in humans reduce disease risk.
CALERIE trial of moderate calorie restriction in overweight human subjects
ongoing.

Much of CALERIE study is to investigate practicality of doing human CR
research - compliance issues.

He's really excited about changes in gene expression as a result of CR.
Looking for CR mechanisms and mimetics.

Question: Likelihood that CR will extend maximum human lifespan? Has
mechanism that benefits lifespan been "used up" evolutionarily, in humans?

He doesn't think so. He thinks CR mechanisms should still likely be present
and work in humans.

Question: What should we as CR Society due to help?

Opportunities to participate in research studies are important.

Question: Michael Rae asked about failure to see mortality rate doubling
time change in CR, Either early or late onset CR.

Yes, the survival curve proceeds at same rate once it starts,

He has recent data started at 14 months of age (human equivalent of 42), and
they saw 13% increase in max lifespan. Perhaps a bit less than a decade in
humans.

Late onset - he'd be surprised if healthy human of age 50-60 doesn't exhibit
metabolic shift as a result of CR.

Question: CR's impact on sleep?

Doesn't know of any studies on sleep in calorically restricted animals.