Fasting & autophagy

Fasting is one of the most talked-about ideas in longevity. The claim usually goes like this: stop eating for long enough and your cells start cleaning themselves out, clearing damaged parts and slowing ageing. There's real science behind that idea. There's also a large gap between what's been shown in animals and what's been shown in people.

What autophagy is

Autophagy means "self-eating". It's the cell's recycling system: damaged proteins and worn-out parts are broken down and their building blocks reused. Yoshinori Ohsumi won the 2016 Nobel Prize in Physiology or Medicine for discovering how it works.

Autophagy is one of the twelve hallmarks of ageing: as we get older, the recycling slows down and damage builds up. When food is scarce, the body's nutrient sensors shift. Growth signals such as mTOR switch off, energy sensors such as AMPK switch on, and autophagy ramps up.

What we know from animals

In yeast, worms, flies and mice, eating less or fasting reliably switches on autophagy, and calorie restriction extends lifespan in many species. In several of these animals, blocking autophagy removes part of that benefit. That's where most of the excitement comes from.

What we know in people

This is where it gets harder.

Autophagy is very difficult to measure in humans. There's no simple blood test for it. Most human evidence is indirect, and what exists suggests the meaningful changes come with longer fasts, measured in days rather than hours. Whether a 16-hour eating window does much for autophagy is simply unknown.

Time-restricted eating works mainly by helping people eat less. In a year-long trial published in 2022, people who ate within an 8-hour window and cut calories lost about the same weight, and saw similar changes in blood pressure, glucose and cholesterol, as people who cut the same calories with no time limit. An earlier 16:8 trial found only small weight loss, no better than the control group, and some of it came from muscle.

Alternate-day fasting has performed about as well as ordinary calorie restriction in trials, with more people dropping out.

Longer fasts and "fasting-mimicking" diets (a few days a month of a very low-calorie, low-protein plan) have shown improvements in weight, blood pressure and some markers of ageing in small studies. The results are interesting, but they're early and need larger, longer trials.

The trade-off: muscle

Long fasts and heavy restriction can cost muscle, especially in older adults and people who don't train. Muscle is one of your strongest assets for healthy ageing. If you fast, protect it: strength training, and enough protein in the hours you do eat.

Who shouldn't fast

Don't try extended fasting without medical supervision if you:

• take insulin or other medication that lowers blood sugar
• are pregnant or breastfeeding
• are underweight, or have a history of disordered eating
• are under 18
• have a medical condition or take medication affected by meals

A sensible way to use it

• A 12-hour overnight fast suits almost everyone: dinner at 7pm, breakfast at 7am. It's easy, and it pairs naturally with better sleep.
• Finish eating 2–3 hours before bed. Good for sleep, reflux and night-time blood sugar.
• If a shorter eating window helps you eat less, use it. Just don't expect magic from the clock itself, and keep your protein up.
• Move. Exercise also switches on autophagy, at least in muscle in animal studies, and it comes with every other benefit in this course.
• Longer fasts belong in the Optimized level, if at all, and ideally with a doctor involved.

Key numbers
2016: the Nobel Prize for discovering how autophagy works.
12 hours: an overnight fast that suits almost everyone.
0: the extra benefit of time-restricted eating over the same calorie cut, in a year-long trial.

This week

• Try a 12-hour overnight window for five days.
• Set a last-food time 2–3 hours before bed and keep it.
• If you already fast, check you're still getting protein at every meal.

In the journal

"No food 3 hours before bed" is one of the most common stop boxes, and your last-food time goes on your nutrition plan, page 20.

Sources: Ohsumi, Nobel Lecture 2016 · López-Otín et al., Cell 2023 · Liu et al., New England Journal of Medicine 2022 · Lowe et al., JAMA Internal Medicine 2020 · Trepanowski et al., JAMA Internal Medicine 2017 · Wei et al., Science Translational Medicine 2017 · de Cabo & Mattson, New England Journal of Medicine 2019