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Fasting and autophagy: what the research shows

Autophagy won a Nobel Prize. Fasting is said to switch it on, clear out "damaged cells" and slow ageing. The first part is true. The rest is mostly mouse data and a few small human trials.

A watercolour pink teacup on a saucer beside a brass alarm clock

What autophagy is

Autophagy means "self-eating". Cells wrap worn-out proteins and damaged parts in a membrane and break them down for reuse. Every cell does this all the time. It is housekeeping and recycling, and it rises when cells lack nutrients.

The Japanese biologist Yoshinori Ohsumi won the 2016 Nobel Prize in Physiology or Medicine for discovering how it works. In the early 1990s he used baker's yeast to identify genes essential for autophagy. The prize honours that mechanism. It does not say that fasting slows ageing in people.

What animal studies show

A 2004 study by Mizushima and colleagues, co-authored by Ohsumi, used mice with a fluorescent autophagy marker. Nutrient starvation induced autophagy in most tissues, to different degrees by organ, and some tissues showed autophagy without starvation.

That shows autophagy responds to starvation in mice. It does not show that fasting slows ageing in people.

What human studies show

Researchers measure autophagy in people indirectly, for example by gene activity in blood cells.

A 2019 trial by Jamshed and colleagues put 11 overweight adults through two 4-day schedules in random order: food between 8 am and 2 pm, or between 8 am and 8 pm. On the early schedule, the autophagy gene LC3A and the ageing-related gene SIRT1 were more active before breakfast. The authors say it "may also increase autophagy". It is a short, small study, and a changed gene reading is not a proven health benefit.

Time-restricted eating against other plans

Time-restricted eating means eating within a fixed window, such as eight hours, and fasting for the rest. de Cabo and Mattson reviewed the animal and human research on intermittent fasting in the New England Journal of Medicine in 2019.

Two randomised trials tested it against ordinary eating plans. Lowe and colleagues (JAMA Internal Medicine 2020, 116 adults with overweight or obesity, 12 weeks) compared eating between noon and 8 pm with three structured meals a day. Weight fell 1.17% in the window group and 0.75% in the control group, not a significant difference. Liu and colleagues (NEJM 2022, 139 adults with obesity, 12 months) gave everyone a calorie-restricted diet and added an 8 am to 4 pm window for half. Weight loss was 8.0 kg with the window and 6.3 kg without, not a significant difference.

In both trials the eating window added no significant weight-loss benefit.

Limits and cautions for women in midlife

A reasonable, low-risk approach

If a gap between dinner and breakfast suits you, that is your call. Stay strong, well-nourished and energetic, and stop if you do not.

Put first what the guidance supports: enough protein (see the Wai diet for the Australian figure) and resistance training twice a week. Treat autophagy as interesting science, not a reason to skip breakfast.

Sources

  1. Nobel Prize in Physiology or Medicine 2016: Yoshinori Ohsumi, for discoveries of mechanisms for autophagy (press release)
  2. Mizushima N et al. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 2004
  3. de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease. N Engl J Med 2019
  4. Jamshed H et al. Early time-restricted feeding improves 24-hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients 2019
  5. Lowe DA et al. Effects of time-restricted eating on weight loss and other metabolic parameters in women and men with overweight and obesity: the TREAT randomized clinical trial. JAMA Intern Med 2020
  6. Liu D et al. Calorie restriction with or without time-restricted eating in weight loss. N Engl J Med 2022
  7. Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer 2017

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