Can extreme calorie restriction enhance human lifespan? (Attia)

#1

The never-ending story of caloric restriction…

A study in mice demonstrated impressive lifespan extension with extreme calorie restriction, but will results translate outside a research setting?

To test how different dietary patterns influence both healthspan and lifespan—and to probe possible mechanisms behind caloric restriction’s effects—researchers Di Francesco et al. tested nearly 1,000 genetically diverse female mice over their natural lifespans. Their goal was to directly compare the lifespan-extending effects of CR, in which total available food was limited, with IF, in which food is withheld entirely for designated periods before resuming normal eating. By examining both approaches in a genetically varied population, the researchers set the stage for a comprehensive look into the impacts of not only caloric intake, but also meal timing and genetic background.

At six months of age—roughly equivalent to 30 years of age for humans—the mice were assigned to one of five groups:

  1. Control: unlimited food access
  2. 20% CR: 20% fewer calories than baseline
  3. 40% CR: 40% fewer calories than baseline
  4. IF 1 day/week: one day of fasting each week
  5. IF 2 days/week: two days of fasting each week

Results revealed a dose–response relationship between calorie restriction and longevity: the greater the sustained calorie reduction, the greater the lifespan extension. Mice on a 20% calorie restriction lived 18.2% longer than controls, while those on 40% restriction had the largest gain—a 36.3% increase in median lifespan. This relationship was even more striking for maximum lifespan: the longest-lived mice in the 20% CR group lived 22.3% longer than their control counterparts, and the 40% CR group lived an astounding 38.4% longer.

6 Likes
#2

Even if it does, I don’t think I could stand calorie restriction. I want to enjoy my life!

3 Likes
#3

We deserve a drug mix to make 40% calories restriction sustainable without mental effort, hacking our brain.

Almost a year ago, I’ve tried for a couple of months naltrexone and have to say it did helped in maintains a low hunger while doing CR 30% .

It would be nice to experiment a bit hunger suppression to make CR comfortable in a life-long sustainable way.

Fabio

2 Likes
#4

Don’t Semaglutide and Tirzepatide already do this?
Maybe not “extreme CR”, but maybe “optimal CR”.
Even better ones on the near horizon.

I know the forum has had discussions about this, but just to recap my recent survey of this stuff…

Compounded Semaglutide:

  • available for around $200 per month.
  • one should save something on food costs.
  • closet of clothes that one keeps hoping they’ll fit into again, seems attainable;-)
  • lowers systemic inflammation
  • mitigate some autoimmune conditions (allergies, psoriasis, … other?)

Contra indications:

  • medullary thyroid carcinoma
  • Multiple Endocrine Neoplasia syndrome type 2.
  • allergic reactions to the medication or its ingredients.
  • history of pancreatitis.
  • pregnancy or breastfeeding
  • women should stop 2 months before a planned pregnancy.

Common side effects

  • gastrointestinal (tend to decrease over time).
  • bloating, gas, belching, heartburn, fatigue, and headache.

Serious side effects and risks although rare

  • thyroid tumors based on animal studies, though the risk to humans is unclear.
  • pancreatitis are possible.
  • hypoglycemia (with other diabetes medications.
  • gastrointestinal issues can lead to dehydration and kidney injury.
  • gallbladder problems.
  • diabetic retinopathy may worsen.
  • increase in resting heart rate possible.
  • allergic reactions can
  • aspiration during anesthesia due to slowed stomach emptying.
  • Mood changes, including suicidal thoughts,

Loose the weight. Try to dial in a lower maintenance dose.

Seems like a significant compliment (at this point) to rapamycin and THT (for men).

Other thoughts appreciated.

3 Likes
#5

What I find interesting is that CR is best for long term outcomes, but then I always hear it’s worse for one to be underweight as we get older. Do you think this strictly about sarcopenia?

#6

sglt 2 inhibitors can create an artificial calorie deficit.

2 Likes
#7

Yes - that would be interesting. But I wonder if the difference would be significant from the alternative approach of blocking mTOR via rapamycin which accomplishes almost the same thing without the need for a new drug.

1 Like
#8

Dr. Michael Lustgarten did a 74 minute video about this that is most certainly worth watching.

I would really encourage you to check it out and not just read the AI summary too.

2 Likes