Thursday, July 17, 2025
Tuesday, July 15, 2025
Monday, July 14, 2025
Is Calorie Restriction Overrated For Longevity? @Unaging.Crissman.Loomis
Comment
The exceptions to rate of living theory were explained by membrane pacemaker theory. Some have argued against it based on polyunsaturate composition of membranes but even here mitochondrial membrane differences and differences in other membrane molecules like plasmalogens explains this exceptions.
All in all reducing damage production explains between species differences in lifespan and also the way things like calorie restriction work.
Too severe CR is not good for humans at least Ive heard of some severe CR practitioners suffering significant bone loss.
I think 2 to 3 days of fasting mimicking diet combined with 4 to 5 days of high food based calcium intake with d3 k2 is probably good.
That said substances that improve mitochondrial function like urolithin a ergothioneine and pqq sound promising. As is sources of plasmalogens or their precursors.
But with age membranes are changed such that their function worsens and they are more easily damaged. Iirc these is due to changes in composition and the origin of these detrimental changes are unknown. But Calorie Restriction opposes the body changing membranes in detrimental ways. Also CR opposes many detrimental gene expression changes. And it also has lots of good changes to parameters.
A brief comment on the membranes the membrane pacemaker theory of aging is based on membrane damage not being simple damage but the creation of autocatalytic reactive molecules able to cross both lipid and acqueous compartments damaging all parts of the cell including dna.
Sunday, July 13, 2025
A link to the paper covering details of membrane pacemaker theory of aging
More than 100 years ago, Max Rubner combined the fact that both metabolic rate and longevity of mammals varies with body size to calculate that "life energy potential" (lifetime energy turnover per kilogram) was relatively constant. This calculation linked longevity to aerobic metabolism which in turn led to the "rate-of-living" and ultimately the "oxidative stress" theories of aging. However, the link between metabolic rate and longevity is imperfect. Although unknown in Rubner's time, one aspect of body composition of mammals also varies with body size, namely the fatty acid composition of membranes. Fatty acids vary dramatically in their susceptibility to peroxidation and the products of lipid peroxidation are very powerful reactive molecules that damage other cellular molecules. The "membrane pacemaker" modification of the "oxidative stress" theory of aging proposes that fatty acid composition of membranes, via its influence on peroxidation of lipids, is an important determinant of lifespan (and a link between metabolism and longevity). The relationship between membrane fatty acid composition and longevity is discussed for (1) mammals of different body size, (2) birds of different body size, (3) mammals and birds that are exceptionally long-living for their size, (4) strains of mice that vary in longevity, (5) calorie-restriction extension of longevity in rodents, (6) differences in longevity between queen and worker honeybees, and (7) variation in longevity among humans. Most of these comparisons support an important role for membrane fatty acid composition in the determination of longevity. It is apparent that membrane composition is regulated for each species. Provided the diet is not deficient in polyunsaturated fat, it has minimal influence on a species' membrane fatty acid composition and likely also on it's maximum longevity. The exceptional longevity of Homo sapiens combined with the limited knowledge of the fatty acid composition of human tissues support the potential importance of mitochondrial membranes in determination of longevity.
Wednesday, July 2, 2025
Tuesday, July 1, 2025
Harvard, MIT: AI's Potemkin Understanding
very nice discussion of an intriguing paper covering some of the limits of the current llms.
Subscribe to:
Posts (Atom)