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Today Interview with Luigi Fontana


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Dear all, Luigi Fontana today has given a lectureb(in Italian) at the Normal School of Pisa (a a fantastic Institution for me!, Enrico Fermi attended that school) . The link is the following: https://www.youtube.com/watch?v=jLZ-obUVOWU   There are some interesting points in his talk. (you can see the slides he commented) As soon as I have time I will try to summarize them here.


all the best, Cloud

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Dear all, I'll try to provide a summary of Luigi Fontana 's conference in Normal School of Pisa.Link:  



I am not so good in English and I have also a very limited time to review the text, so forgive me for mistakes and misprints.

TAke into account that the conference was for a generic public.  I will translate the slides I have found more interesting.

The time reference of the slides is only indicative.



Approach centered on prevention (with the development of nutritionals/exercise/pharmocological intervents that block the accumulation of molecular/metabolic/cell damage – inhibition of pro aging signaling paths) at about 6:40


reference: Fontana et al., Nature, 2014


Secrets of longevity (he says that he is simplifying)


N.1 The most important thing, on which there is a total consensus, is the need to be slim and avoid accumulation of addominal fat

at about 8:40

(see TAC image of abdome) at about 9:35

abdominal fat produces cytokines and hormones (at 9:55)

also thin people when increase the waist circumference increase the mortality risk (11:18)

The effort must be to limit the natural increasing of waist circumference (reference values at 11:39)


What are the actions that help us to maintain a flat abdomen? (12:05)

1) calorie restriction

2) intermittent fasting

3) physical activity


From 12:10 he describes the results of CR


He says that hundreds of studies have confirmed the initial results (living longer and protected from tumors) in rodents (at 12:45)

For him the CR without malnutrition is the most powerful intervention for preventing carcinogen genesis

Reference: Albanes, Cancer Research, 1987


at 13.14 he says that the most fascinating thing for him is that 1/3 die without developing disease

Shimokawa I et al. J. Gerontology 1993

This suggest that mammals can live long without getting sick

He says that 20 % of centenarians are “escapers”

Therefore also human beings can become sick only in the last part of existecnce.


At (14:09) he summarize the animal Models of longevity (for murine models)


nutritionals methos: CR & IF, protein restriction & methionine,

two drugs: rapamicin, acarbose

in red he underlines the models that share a down regulation of insulin / IGF-1 / mTOR pathways

Reference at 15:39: Fontana et al. , Science 2010


Several studies on monkeys (16:10)

He says there are a number of studies, for simplicity he shows only one.


Humans: he says there are various studies, an example at 16:30

Reference: Fontana et al. , Science 2010

at 18: 33 he presents CR influenced factors associated to a minor risk of cancer.

Step forward on CR applicability to humans: at 19:44 Mercken et al. ; Aging Cell, 2013

Slide at 20:00: he presents the scheme that shows in humans (in the muscle) there is the inhibition of the IGF-1/Insulin pathway and increase FOXO


To summarize: For Fontana also in humans the CR implements from the molecular point of view some pathways that slow down the accumulation of molecular damage

--just released report in Cell Reports: http://www.cell.com/cell-reports/fulltext/S2211-1247(15)01483-7


Then he presents intermittent fasting (IF), that also extends the lifespan of the mice (30% 40% more)

at 22.40

Reference: Longo and Mattson Cell Metabolism 2014

Fontana and Partridge, Cell 2015

At 24:48 he presents randomized trial at Washington University in which people don't try water fasting,but they can eat raw and cooked vegetables with just a tablespoon of olive oil (100 kcal) for two or three days a week.

The study is not finished yet but the initial results are fantastic: weight loss, improved fat mass, etc. 

According to him this could be a easier way to help people to maintain a normal weight and it has a strong biological basis because IF in animals lengthens life and prevents disease


at 24:48 he tells of experiments about meal times (circadian rhythm) for two isocaloric diets 1) BF breakfast 2) the opposite

best values for group 1)

from these studies is emerging the consideration that it is better to not eat many meals during the day, but concentrate most of the calories in the first part of the day and have a very light dinner, in order to maintain the body in a fasting state as long as possible and not activate the Insulin / IGF 1 / mTOR pathway


at 26.40 he summarize the importance of the physical exercise (especially for fat mass)


At 30:00 he speaks of the quality of diet, an excerpt from an article of Ancel Keys


At 34:00 he examines studies on protein restriction (with unpublished data)


with protein restriction increases the hormone prolongevity FGF-21 (at 35.30)


At 36:00 he speaks of microbioma

protein and fiber are the more important nutritional factors for the regulation of microbioma.



at 42:20 he summarizes other important points for longevity (Vitamin D, sleep, meditation, etc.)


At 48:00 he presents the “Healthy Longevity” puzzle

he expects that in the next 15-20 years they will be able to do some amazing things


QA Time (from 50:00)

Interesting questions and answers, in particular:


at 1:14:50 he says that he believe in a certain role for animal food (in small quantity) . For example for B12

at 1:17:55 two questions from another noted researcher (Alessandro Cellerino):

<<Of the various strategies proposed by Fontana which, in his opinion, is easier to apply for general public? And the common mechanism is the hormesis?>>

Fontana answers that the question is complicated. Some dogmas like that “only calorie are important” are no longer considered valid. He says that for him is not only hormesis.

The problem is that they at the moment are not able to make a scale of importance of the various mechanisms for longevity. (at 1:20:20) There are still many things to understand. if the goal is to live 200 years we have not yet the knowledge. If the goal is to prevent the the majority of chronic degenerative diseases we can. The problem is that physical exercise make somethings on some signalling pathways, protein restriction does some other things, and so fasting, CR, and fatty acids...there is not an intervention that does everything . This is the problem. It is not true that only calorie are important. He concludes by saying: << we are not there yet >>



It was for me an interesting conference, I hope this summary will be useful for someone.

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