FoundMyFitness · 2017-07-31 · Rhonda Patrick (host), Guido Kroemer
Dr. Guido Kroemer on Autophagy, Caloric Restriction Mimetics, Fasting & Protein Acetylation
40 claims checked against research: 1 contradicted 2 overstated 3 needing context 30 supported 4 unverified
2 Overstated
In mice, alternate-day intermittent fasting extends lifespan to the same extent as 30% caloric restriction without resulting in a permanent reduction in body weight.
"in mice, you can obtain exactly the same longevity extension that you would obtain with 30% of caloric restriction by intermittent fasting... the intermittently fasted mouse has the same weight as a normally fed mouse. In difference with the calorically restricted mouse, it weighs also 20 to 30% less. And in spite of this difference in the body weight, intermittent fasting allows for lifetime expansion in the same way as does caloric restriction." (said at 0:21:30)
While some rodent studies have shown that alternate-day intermittent fasting can extend lifespan without reducing overall body weight due to compensatory hyperphagia on feeding days, this effect is highly conditional rather than universal. Preclinical research demonstrates that the impact of every-other-day feeding on body weight and longevity in mice is strongly dependent on genetic background, age of onset, and fasting regimen. In certain inbred strains (such as C57BL/6J), intermittent fasting does lead to significant body weight reduction, and large-scale assessments across genetically diverse mice demonstrate that continuous caloric restriction generally provides more robust lifespan extension than intermittent fasting regimens.
- partial: Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction … (Mechanisms of ageing and development 1990) · cited 285x in the literature
"Relative to estimates for ad libitum controls, the body weights of the intermittently-fed restricted C57BL/6J and hybrid mice were reduced and mean and maximum life span were incremented when the every-other-day regimen was initiated at 1.5 or 6 months of age... Among A/J mice, intermittent feeding did not reduce body weight relative to ad libitum controls when introduced at 1.5 or 10 months of age; however, this treatment did increase mean and maximum life span when begun at 1.5 months, while it decreased mean and maximum life span when begun at 10 months... These results illustrate that the effects of particular regimens of dietary restriction on body weight and life span are greatly dependent upon the genotype and age of initiation." (abstract, results, passage verified)
pubmedfull study (doi) - partial: Dietary restriction impacts health and lifespan of genetically diverse mice. (Nature 2024) · cited 178x in the literature
"We show that caloric restriction and intermittent fasting both resulted in lifespan extension in proportion to the degree of restriction. Lifespan was heritable and genetics had a larger influence on lifespan than dietary restriction... 40% caloric restriction had the strongest lifespan extension effect but led to a loss of lean mass and changes in the immune repertoire that could confer susceptibility to infections. Intermittent fasting did not extend the lifespan of mice with high pre-intervention body weight" (abstract, results, passage verified)
pubmedfull study (doi)
Long-term clinical efficacy of chemotherapy depends on inducing cancer cell death that elicits an anti-cancer immune response via autophagy induction.
"chemotherapy must provoke this cell death in a way that it later leads to an immune response. And so, if you have a long-term effect of chemotherapy for years or decades, that continues beyond removal of the drug. It is due to an anti-cancer immune response. And so, since this is so important, the capacity of the chemotherapeutic agent to induce autophagy is actually required for the long-term efficacy of the treatment." (said at 0:48:21)
The speaker generalizes findings from the immunogenic cell death (ICD) paradigm to all long-term chemotherapy efficacy. Preclinical studies in mouse models and cancer cell lines (such as those by Michaud et al., 2011, 2012) established that certain chemotherapeutics (e.g., anthracyclines, oxaliplatin) require premortem autophagy to release ATP, recruit dendritic cells and T cells, and achieve durable immune-mediated tumor control. However, asserting that any long-term remission lasting years or decades from chemotherapy is universally dependent on autophagy induction overstates the evidence. Chemotherapeutic agents possess diverse mechanisms of cytotoxicity (e.g., direct DNA damage, mitotic arrest, cellular senescence) that can eliminate tumor clones without ICD, and autophagy in many clinical contexts can conversely promote chemoresistance and tumor survival rather than antitumor immunity.
- partial: Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice… (Science (New York, N.Y.) 2011) · cited 1345x in the literature
"Here we demonstrate that autophagy, which is often disabled in cancer, is dispensable for chemotherapy-induced cell death but required for its immunogenicity. In response to chemotherapy, autophagy-competent, but not autophagy-deficient, cancers attracted dendritic cells and T lymphocytes into the tumor bed." (abstract, results, passage verified)
pubmedfull study (doi) - partial: Premortem autophagy determines the immunogenicity of chemotherapy-induced cancer cell deat… (Autophagy 2012) · cited 106x in the literature
"However, autophagy-incompetent cancers fail to release ATP, to recruit immune effectors into the tumor bed and to respond to chemotherapy in conditions in which autophagy-competent tumors do so." (abstract, results, passage verified)
pubmedfull study (doi) - partial: An autophagy-dependent anticancer immune response determines the efficacy of melanoma chem… (Oncoimmunology 2014) · cited 77x in the literature
"Most of the preclinical evidence supporting this notion has been obtained with transplantable cancers, for which it has been shown that chemotherapy-induced autophagy in cancer cells is mandatory for the recruitment of myeloid cells into the tumor bed and the subsequent T lymphocyte-mediated reduction in tumor growth." (abstract, results, passage verified)
pubmedfull study (doi)
Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.