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Valter Longo

University of Southern California

Valter Longo is the director of the Longevity Institute at the University of Southern California and the Oncology and Longevity Program at the Institute of Molecular Oncology Foundation in Milan, Italy. His research focuses on the biological mechanisms governing the aging process and the roles of diet, caloric restriction, and fasting in human healthspan. His publications explore the therapeutic and metabolic impacts of fasting-mimicking diets across various conditions, including cancer, type 2 diabetes, and cardiometabolic diseases.

27 claims checked on air: 2 context 1 contradicted 21 supported 3 unverified 1 flagged

What they said on air - citing their own research

12 citing their own research

0:11:48supportedmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

Individuals in Ecuador with growth hormone receptor deficiency (Laron syndrome) are protected from cancer, diabetes, and age-dependent cognitive decline.

"and in our work in humans where we've been following these people with the growth hormone receptor deficiency down in Ecuador—they have a syndrome called Laron syndrome—so they're very much the equivalent to the mice, and they don't have a very long lifespan. They may live a few years more than their relatives that don't have homozygous growth hormone receptor deficiency, but they're protected from cancer, they're protected from diabetes, and recent papers show that they seem to be protected from age-dependent cognitive decline." (said at 0:11:48)

Longitudinal and cross-sectional studies of the Ecuadorian cohort with growth hormone receptor deficiency (GHRD / Laron syndrome) confirm that these individuals have a near-total absence of diabetes and a marked reduction in cancer incidence compared to unaffected relatives. Furthermore, neuroimaging and cognitive evaluations of this cohort demonstrated preserved memory performance and brain structure/function resembling that of younger adults, suggesting protection against age-dependent cognitive decline.

0:13:14supportedmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

Circulating IGF-1 levels in individuals with Laron syndrome are approximately 10% of normal circulating IGF-1 levels.

"Yeah, we measured the IGF-1. It's very low. It's like 10% of the normal circulating IGF-1." (said at 0:13:14)

Individuals with Laron syndrome (growth hormone receptor deficiency/growth hormone insensitivity) have severe primary IGF-1 deficiency. Published biochemical evaluations in cohorts with Laron syndrome show extremely low circulating levels of insulin-like growth factor-1 (IGF-1), typically reduced to approximately 10% (or less) of normal control levels, accompanied by normal to elevated growth hormone levels and low or undetectable growth hormone-binding protein.

0:17:05supportedvery lowtheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

In mammalian cells, glucose levels directly activate Protein Kinase A (PKA).

"Actually, we've shown that as we have shown for yeast, we've now shown in mammalian cells that glucose levels activate PKA." (said at 0:17:05)

Preclinical studies from Valter Longo's laboratory demonstrated that glucose levels regulate protein kinase A (PKA) signaling in mammalian cell models and mice, mirroring the glucose-PKA nutrient sensing pathway previously characterized in yeast. Specifically, experimental work in mammalian cardiomyocytes and cancer stem cells showed that glucose availability stimulates PKA activity, whereas glucose restriction or fasting-mimicking conditions reduce PKA activation. Because these findings are derived from cell culture and rodent experiments, the clinical certainty remains very low.

0:27:00supportedmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

In clinical trials testing fasting-mimicking diets alongside cancer treatment, subject compliance was approximately 40% due in part to chemotherapy-induced food aversion.

"So we already—a couple hundred patients have already been involved in these multiple randomized clinical trials, and the good news is that there is no problems... So we had about a 40% thus far compliance" (said at 0:27:00)

Clinical trials evaluating cyclic fasting-mimicking diets (FMD) alongside chemotherapy in cancer patients (such as the multicentre randomized phase 2 DIRECT trial in breast cancer) have documented overall compliance rates of approximately 33% to 40% across all planned cycles. The decline in adherence across repeated treatment cycles is commonly driven by chemotherapy-associated side effects, including nausea, taste alterations, and food aversion toward the FMD components.

0:32:10supportedmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

In clinical trials, the fasting-mimicking diet does not further lower fasting glucose in individuals with normal baseline glucose around 75 mg/dL, but normalizes fasting glucose in individuals with levels over 106 mg/dL.

"Fasting glucose—the fasting-mimicking diet says it seems when if you have a blood glucose of 75, nothing changes, it doesn't drop it even more. If you had a fasting glucose over 106, almost in every case it brings you back to normal." (said at 0:32:10)

A randomized controlled trial evaluating cycles of a 5-day fasting-mimicking diet (FMD) demonstrated differential effects based on baseline metabolic risk. In a post hoc analysis, risk factors including fasting glucose were selectively and more beneficially reduced in participants with elevated baseline risk factors, whereas participants with healthy baseline levels experienced minimal change, maintaining normal glucose levels without excessive reduction.

0:33:14supportedmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

Three cycles of the fasting-mimicking diet significantly reduced cholesterol, triglycerides, IGF-1, systolic and diastolic blood pressure, and CRP in participants who had elevated baseline levels, with IGF-1 dropping by roughly 60 points in those with the highest baseline levels.

"But in people who had elevated cholesterol, it decreased cholesterol. The people that had elevated triglyceride, it decreased triglycerides. People that had elevated IGF-1, probably for even a high-protein diet, it dropped IGF-1, and the highest people dropped dramatically, you know, came down about 60 points. And people that had high fasting glucose came down. People had blood pressure that was elevated, both systolic and diastolic had major effects. The people who had CRP, systemic inflammation, in almost every case they moved back to the the normal range." (said at 0:33:14)

A randomized controlled trial evaluated 100 participants completing three monthly 5-day cycles of a fasting-mimicking diet (FMD) versus an unrestricted control diet followed by crossover. The primary analysis demonstrated significant reductions in body weight, blood pressure, and IGF-1. A post hoc stratified analysis of participants with elevated baseline risk factors confirmed that participants with elevated baseline levels experienced significantly greater reductions in total and LDL cholesterol, triglycerides, fasting glucose, systolic and diastolic blood pressure, IGF-1, and C-reactive protein (CRP), with IGF-1 falling most substantially among those in the highest baseline tier.

0:35:35supportedmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

Approximately 60% of the biomarker changes achieved after three cycles of the fasting-mimicking diet remained statistically significant three months post-intervention.

"I mean, they were about 60% of the effects were still there. So you could tell that they were smaller, but 60% of the changes were still significant." (said at 0:35:35)

In a randomized trial evaluating 100 healthy participants undergoing three monthly 5-day cycles of a fasting-mimicking diet (FMD; PMID: 28202779), post-intervention follow-up after participants returned to their normal diet showed that approximately 60% of the significant metabolic and risk-factor reductions (such as body weight, trunk fat, blood pressure, and IGF-1) persisted.

0:41:41supportedvery lowtheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

Mice placed on cycles of the fasting-mimicking diet eat the same total monthly caloric intake as controls due to compensatory refeeding, but still experience significant weight loss and fat burning.

"we've shown that per month, if you take mice and you put them on fasting-mimicking diet, they, you know, of course have less calories during the five-day—the four days in the case of mice—and but then their metabolism seems to be speeded up to the point that per month they eat the same calories, so they overeat everything they undereat during the the the five—the four days, right? So they eat exactly the same, but they lose a lot of weight." (said at 0:41:41)

In animal studies evaluating periodic fasting-mimicking diet (FMD) regimens (such as Brandhorst et al., 2015), mice underwent 4 days of FMD cycles followed by ad libitum refeeding. During the refeeding periods, the mice exhibited compensatory hyperphagia, resulting in equivalent total monthly caloric intake compared to ad libitum-fed controls, while still displaying significant reductions in body weight, visceral fat, and age-related biomarkers. Because the claim describes findings specifically demonstrated in rodent models, the overall certainty is rated very low.

0:43:07needs contextmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

The fasting-mimicking diet selectively reduces abdominal fat while sparing subcutaneous fat and preserving or increasing relative lean body mass following refeeding in humans and mice.

"and of course you lose abdominal fat because after a few days this becomes your reservoir. I mean, every—although all the—it doesn't touch subcutaneous fat for some reason, it only goes to the main depot that have this effect. So that's great news, but the muscle is also decreased. But then when you refeed, the muscle is rebuilt... and this, no effect on subcutaneous fat and no or very little effect on even absolute lean body mass. In fact, the relative lean body mass goes up." (said at 0:43:07)

Randomized trial data on periodic cycles of the fasting-mimicking diet (FMD) in humans (such as the 100-subject trial by Wei et al., 2017) show that 3 monthly cycles of FMD reduce trunk and total body fat while largely preserving absolute lean mass and increasing relative lean body mass after normal refeeding. However, stating that FMD has 'no effect on subcutaneous fat' or 'doesn't touch subcutaneous fat' is an exaggeration; while visceral/trunk fat is preferentially mobilized, overall body fat decreases as well.

0:45:07supportedmoderatetheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

In mice and humans undergoing fasting or fasting-mimicking diets, organs and white blood cell levels temporarily shrink or reduce during fasting cycles and return to normal levels upon refeeding through stem cell activation.

"so the organs will be smaller and, you know, at the end of the the days of fasting-mimicking diet, and then you refeed it and of course they go back to the normal level, right? So there is really there is this shrinking and re-expanding effect. Now, we don't know how much of it is cells becoming smaller versus cells being killed, but clearly there is killing of cells... And we've started to show that in a multiple sclerosis mouse model, and and also the human study, there was evidence that the white blood cell level temporarily was reduced during the at the end of the fasting cycles and then went back to normal. So yeah, so we suspect that there are these this fasting-dependent depletion of both intracellular components, in autophagy, and cellular components. And then, you know, we've shown the stem cells to be activated and and the stem cell turn on in the refeeding part." (said at 0:45:07)

Preclinical and clinical studies by Longo and colleagues demonstrate that cycles of prolonged fasting or fasting-mimicking diets (FMD) induce a transient reduction in organ size and circulating white blood cell levels, followed by stem cell- and progenitor cell-mediated regeneration upon refeeding. In mice, 4 days of FMD decreased the weight and size of multiple organs, which re-expanded upon refeeding accompanied by elevated stem/progenitor cell numbers. Similarly, prolonged fasting and FMD were shown in mouse models and pilot human trials (including multiple sclerosis cohorts) to deplete white blood cells and auto-reactive immune cells via apoptosis, subsequently triggering hematopoietic stem cell self-renewal and lineage regeneration driven by down-regulation of IGF-1 and PKA signaling.

0:51:21supportedvery lowtheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

In a multiple sclerosis mouse model, fasting-mimicking diet cycles kill autoimmune immune cells, activate stem cells, and stimulate oligodendrocyte progenitor cells to replace damaged cells.

"Because, for example, in multiple sclerosis, you see on one side it kills the immune cells, it then turns on the stem cells, then turns on the oligodendrocyte progenitor, replaces—I mean, it's very sophisticated." (said at 0:51:21)

In a 2016 preclinical study in mouse models of multiple sclerosis (experimental autoimmune encephalomyelitis and cuprizone-induced demyelination), periodic cycles of a fasting-mimicking diet (FMD) reduced levels of pro-inflammatory immune cells (TH1, TH17, and antigen-presenting cells) through apoptosis/depletion, increased regulatory T cells, and promoted oligodendrocyte precursor cell regeneration and remyelination. Because these mechanistic findings derive from animal models, the overall certainty is rated very low.

0:54:23supportedvery lowtheir own paperHow diet and lifestyle regulate longevity with Dr. Valter Lo

Stem cell activation and self-renewal during fasting is low IGF-1 dependent, whereas stem cell proliferation and differentiation during refeeding are driven by high IGF-1 and insulin levels.

"the turning on of stem cells, which is also low IGF-1 dependent. So—oh, it's low? I thought it was higher. GUEST1: Right, the turning on the stem cell, not turning on the proliferation of them. It's high IGF-1—yeah. No, but the—the turning on, all right, so now is the signal, right, to self-renew, you know? Yeah. So now you have a population of—a small population of stem cells that are just active and standing by. Then probably when IGF-1 goes back up, now they are the ones that are pushed by IGF-1 to proliferate, to differentiate" (said at 0:54:23)

Preclinical studies in mice demonstrate that prolonged fasting lowers circulating IGF-1 levels and downregulates PKA signaling, which triggers self-renewal and lineage-balanced priming in long-term hematopoietic stem cells. Subsequent refeeding and restoration of growth factors (including IGF-1) promote the proliferation, differentiation, and multi-system tissue regeneration of these primed progenitor pools. Because the direct causal demonstration of this dual-phase mechanism is derived from murine and in vitro models, the certainty of evidence for this specific cellular pathway in humans is very low.

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