Skip to article
HPC  ·  Science Deep Dive 5 April 2026  ·  revised 2026-04-05

Autophagy & Fasting: The Cellular Recycling Mechanism Behind Metabolic Brain Benefits.

When you stop eating for long enough, your cells begin digesting their own damaged parts, and the brain may be the organ that benefits most. Here is what the science actually says, and what to do with it.

Section
Bio-Performance
Reading time
22 min read
Sources
48 · reviewed

01The 2016 Nobel Mechanism

Cells digest their own damage when you stop eating

Every cell in your body runs a cleanup program. Not the vague "detox" of wellness marketing, not a gentle tidying. It is a controlled demolition: the cell identifies its own damaged parts, wraps them in a membrane, and delivers them to a digestive compartment that breaks them down to raw materials. The amino acids, fatty acids, and nucleotides that come out the other side are recycled into new structures. The Japanese cell biologist Yoshinori Ohsumi mapped the genetic machinery behind this process and won the 2016 Nobel Prize in Physiology or Medicine for it.[26] The word for it is autophagy, from the Greek for "self-eating."

The most reliable way to activate this cellular recycling system is also the oldest: stop eating. When you fast long enough for liver glycogen to deplete (roughly 12 to 16 hours, depending on activity level and metabolic state), a molecular switch flips.[5] The energy sensor AMPK activates. The growth signal mTOR quiets. A cascade of kinase activity opens the gate to autophagy.[1] This is not a modern biohack. It is the cellular response to a condition that, until very recently in human history, was the default: extended periods without food.

The scale of the problem this addresses is hard to overstate. More than one billion people worldwide now live with obesity (approximately 880 million adults and 159 million children and adolescents), and that number has more than doubled since 1990.[19] Obesity is a confirmed suppressor of autophagic clearance. Human biopsies from liver, skeletal muscle, and adipose tissue show impaired autophagy flux in obese individuals, correlating directly with insulin resistance and lipotoxicity.[16] The modern body is overfed and under-recycled.

01 · The history

The brain makes this story personal. For decades, neuroscientists assumed the brain was autophagy-resistant: its privileged metabolic position, steady glucose supply, and status as the body's most protected organ seemed to exclude it from the same recycling programs as the liver or muscle. Alirezaei and colleagues overturned that assumption in 2010 when they demonstrated a three- to fourfold increase in autophagosomes in mouse cortical and Purkinje neurons after short-term food restriction, the first direct evidence that neurons not only perform autophagy but dramatically upregulate it during fasting.[13]

That finding reframed the conversation. If the brain is not autophagy-resistant, then it is also not autophagy-protected when fasting stops happening. Impaired neuronal autophagy permits the accumulation of misfolded proteins: amyloid-β, α-synuclein, tau, the molecular hallmarks of Alzheimer's, Parkinson's, and other neurodegenerative diseases.[30][36] A body that never fasts may be a body whose neurons never fully clear their waste.

The first controlled human data are now arriving. In 2025, Bensalem and colleagues published the first randomized controlled trial measuring autophagic flux in humans as a primary outcome. They found that intermittent time-restricted eating produced significantly higher flux markers than standard care at six months, while calorie restriction alone did not.[4] The fasting period itself, not merely the calorie deficit, appeared to be the active variable. The clinical evidence is early-stage. But the direction is clear.

02The Mechanism

The Molecular Switch That Turns Fasting Into Cellular Recycling

The core mechanism of autophagy fasting science is a molecular rivalry. Two kinases, AMPK (the cell's energy sensor) and mTOR (the cell's growth promoter), compete for control of a single downstream target: a kinase called ULK1. When nutrients are abundant and the cell has energy to spare, mTOR phosphorylates ULK1 at an inhibitory site (Ser757), blocking autophagy. The cell builds. When nutrients disappear and the AMP-to-ATP ratio rises, the molecular signature of an energy deficit, AMPK activates and phosphorylates ULK1 at activating sites, overcoming mTOR's grip. The cell recycles.[1]

The canonical model, established by Kim and colleagues in 2011 and replicated extensively across organisms and tissue types, identified this as a direct phosphorylation switch: AMPK at Ser317 and Ser777 versus mTOR at Ser757, on the same substrate.[1] More recent work has proposed refinements to the precise site assignments. Two independent research groups have challenged whether Ser317 and Ser777 are the definitive activating sites, with evidence suggesting additional regulatory complexity at the ULK1 node.[31] The functional outcome is not in dispute: AMPK promotes and mTOR suppresses autophagy at ULK1. The mechanism remains an area of active investigation at the site-assignment level, but the kinase-competition architecture is settled science.

That matters because the switch is not gradual. It has a threshold. When hepatic glycogen depletes, typically after 12 to 16 hours of fasting, the liver shifts from glucose export to fatty acid oxidation and ketogenesis.[5] The resulting rise in circulating ketones, particularly β-hydroxybutyrate (BHB), signals the energy shift systemically. AMPK activates. mTOR quiets. The ULK1 complex, now free to function, initiates the formation of the phagophore, the double-membrane structure that engulfs damaged cellular cargo.[2][24]

AMPK 01 energy deficit detected ULK1 02 mTOR grip released Autophagosome 03 cargo engulfed BHB 04 brain ketone rises

The fasting-autophagy cascade: AMPK activation overcomes mTOR suppression at the ULK1 node, the molecular switch that initiates cellular recycling, while fasting-derived β-hydroxybutyrate crosses the blood–brain barrier to fuel neurons and upregulate BDNF.

Diagram · HPC

Once the phagophore forms, the process follows a precise sequence. The membrane elongates around its target (a damaged mitochondrion, a protein aggregate, a lipid droplet) and seals to create an autophagosome. The autophagosome then fuses with a lysosome, a membrane-bound compartment filled with degradative enzymes, and the cargo is broken down into amino acids, fatty acids, and nucleotides.[2][24] These raw materials re-enter the cell's metabolic supply chain. The process is not waste disposal. It is manufacturing: the cell dismantles old parts to build new ones.

The selectivity of this system is what separates it from simple degradation. Mitophagy, the targeted elimination of damaged mitochondria, ensures that the cell's power plants maintain quality control.[39] Aggrephagy targets protein aggregates that would otherwise accumulate and become toxic. The adapter protein p62/SQSTM1 acts as a cargo receptor, tagging damaged components for autophagic degradation.[7] When these selective pathways fail, the consequences are specific and predictable: damaged mitochondria leak reactive oxygen species, protein aggregates seed further misfolding, and cellular function degrades in ways that manifest as aging, metabolic dysfunction, and neurodegeneration.[7][25]

The supporting regulatory network extends beyond the AMPK-mTOR axis. SIRT1, a NAD+-dependent deacetylase activated by fasting, promotes autophagy through Beclin-1 activation. This pathway was confirmed to be required for lifespan extension by caloric restriction in the model organism C. elegans.[14] The natural polyamine spermidine, whose levels rise during fasting, independently induces autophagy. In murine cardiomyocytes, cardioprotection by spermidine was abolished entirely in cells lacking the essential autophagy gene ATG5, confirming that autophagy is the obligatory mediator of spermidine's protective effects.[10][27]

03Evidence

The 5 Strongest Studies on Autophagy Fasting Science

01The claim

The single load-bearing finding

The hero study finds Ser317/777 phosphorylation sites.

Pooled estimate

Ser317/777

02How we measured

Grading the fasting studies

Studies scored on design, sample, rigour, causality, replication.

Autophagy science has a replication asymmetry: the molecular mechanism is replicated globally, but controlled human trials measuring autophagic flux directly only arrived in 2025, so replication depth matters most at the clinical tier.

Rubric weights

Design/35
Sample/20
Rigour/15
Causality/15
Replication/15

03The spread

Heterogeneity across 5 studies

Effect sizes across the ranked studies.

Spread

91 → 74 /100

Range of point estimates across ranked studies.

04What does not hold

Negative knowledge

What the evidence base does not support.

The brain-specific evidence adds a dimension that body-composition studies miss entirely. Mattson's 2024 pilot RCT is the first to show measurable changes in brain metabolism and age estimation on MRI with an intermittent fasting intervention.[15] The effect is modest and the sample small. But the measurement is objective. MRI brain-age-gap estimation is not a self-reported cognitive score; it is a structural assessment of how old the brain looks relative to its chronological age. Nikoletopoulou's 2017 mechanistic work explains why the brain response is not simple activation but selective edi

Consumer dose

The studies

5 trials. One pooled answer.

Below: the anchor study in full; then the forest plot at scale; then the supporting trials in ranked order.

The Key Study Highest rubric · 91/100 · load-bearing

01Anchor

, AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

Kim, Kundu & Viollet 2011 Controlled Molecular Biology · Genetic Confirmation · Replicated

This paper established the precise molecular logic of how fasting triggers autophagy: a kinase competition at ULK1, where AMPK and mTOR phosphorylate competing sites to control initiation. Genetic knockout confirmed necessity, removing AMPK abolished the fasting autophagy response. **Every clinical

Rubric breakdown

Design28/35
Sample14/20
Rigour14/15
Causality15/15
Replication10/10
Citations10/10
Total 91/100

The strongest studies, ranked by methodological weight.

Each scored 0–100 against a six-criterion rubric, tagged by design and year; the anchor leads.

050100 rubric 90 01 Kim, Kundu & Viollet Controlled Molecu… · 2011 91 02 Bensalem, Teong & XT RCT · 2025 82 03 Cabo & Mattson 2019 79 04 Mattson & MP 2024 76 05 Nikoletopoulou, Sidiropoulou & Kallergi 2017 74 rubric score · out of 100
Anchor (Rank 1) Supporting
Rank Authors & title Journal · Year Finding Score

02

Bensalem, Teong & XT

, Intermittent time-restricted eating may increase autophagic flux in humans

· 2025

In 121 adults with obesity randomized to standard care, calorie restriction, or intermittent time-restricted eating for 6 months, the iTRE group showed significantly higher autophagic flux (LC3B-II/I ratio in PBMCs with chloroquine) versus standard care. Calorie restriction alone did not differ from standard care, suggesting the fasting period, not calorie deficit, is the active variable. Within-group change from baseline did not reach significance (exploratory label warranted).

82/100

03

Cabo & Mattson

, Effects of Intermittent Fasting on Health, Aging, and Disease

· 2019

Eating in a 6-hour window and fasting for 18 hours triggers a metabolic switch at 12–16 hours, from glucose-based to ketone-based energy, establishing the practical threshold at which autophagy induction begins. The review synthesized animal and human data to establish this quantified threshold.

79/100

04

Mattson & MP

, Brain responses to intermittent fasting and the healthy living diet in older adults

· 2024

In 40 cognitively intact older adults with insulin resistance, 8 weeks of 5:2 intermittent fasting decreased brain-age-gap estimates on MRI and reduced brain glucose on MRS. On specific measures of executive function and memory, the IF group improved approximately 20% more than the healthy living diet group, though both groups showed benefit, and this is a pilot RCT with replication underway.

76/100

05

Nikoletopoulou, Sidiropoulou & Kallergi

, Modulation of Autophagy by BDNF Underlies Synaptic Plasticity

· 2017

Fasting-induced BDNF signaling via TrkB/PI3K/Akt suppresses hippocampal autophagy; this suppression is required for long-term potentiation and memory enhancement. Restoring autophagy inhibition rescued LTP in hippocampal neurons. In rodent hippocampus, human translation not yet directly tested.

74/100

04Stakes

The Cost of a Cell That Never Cleans House

When autophagic flux declines, through chronic overfeeding, aging, or metabolic disease, four systems pay the price. The damage is cumulative, tissue-specific, and increasingly measurable in human biopsies and imaging.

01 System 01 · System 01

Neurodegeneration

Impaired neuronal autophagy permits accumulation of misfolded proteins, amyloid-β in Alzheimer's, α-synuclein in Parkinson's, huntingtin in Huntington's disease.[30][36] Cognitively intact individuals with Alzheimer's neuropathology maintained higher autophagic capacity than matched cognitively impaired individuals, suggesting autophagy preservation may be neuroprotective even against existing amyloid burden.[37] The brain that never clears its aggregates accumulates the molecular signature of decline.

30
In practice

brain fog, declining short-term memory, slower processing speed, difficulty maintaining focus

02 System 02 · System 02

Metabolic Dysfunction

Human biopsies confirm tissue-specific autophagy impairment in obesity and type 2 diabetes: reduced flux in liver hepatocytes correlates directly with insulin resistance and lipotoxicity.[16] The liver that cannot recycle its damaged organelles becomes the liver that drives metabolic syndrome. Adipose tissue shows paradoxical upregulation, suggesting a compensatory response that fails to restore systemic autophagic balance.[16]

2
In practice

persistent fatigue despite sleep, afternoon energy crashes, stubborn visceral fat, blood sugar instability

03
System 03 · System 03

Cardiovascular Aging

Cardiac autophagy declines with age, leading to damaged organelle accumulation, myocardial dysfunction, and reduced stress resilience.[33][40] Spermidine-induced cardioprotection was abolished entirely in cardiomyocytes lacking the essential autophagy gene ATG5, confirming that the heart's resilience depends on autophagy, not merely on the molecules that trigger it.[10] The aging heart that cannot recycle its damaged mitochondria loses its capacity to respond to stress.

33
In practice

reduced exercise tolerance, slower recovery from exertion, elevated resting heart rate, exercise-induced breathlessness at lower thresholds

04 System 04 · System 04

Accelerated Aging & Sarcopenia

Autophagy and mitophagy decline with age in skeletal muscle; lysosomal dysfunction impairs protein clearance and mitochondrial turnover.[38][35] The result is not just weakness but a progressive loss of the muscle's self-repair machinery. The body that never fasts may be the body that ages in the tissue where aging is most functionally visible: the muscle that moves it.

38
In practice

unexplained strength loss, longer recovery between training sessions, muscle soreness that lingers, reduced grip strength

05Protocol

An Evidence-Informed Fasting Protocol for Autophagy Activation

Four steps derived from the strongest available evidence, not a wellness prescription but a translation of what the molecular, animal, and early human data support. The operating principle: extend the overnight fast past the metabolic switch threshold while protecting muscle and bone.

The protocol, as a sequence.

Daily → Within window → Within window → Weekly

Daily 01 The Fasting Window Within window 02 Protein Protection Within window 03 Resistance Training Weekly 04 Periodic Deeper Fasts
01 Step 01 · Daily

The Fasting Window

Establish a consistent 14–16 hour daily fast (10-hour eating window), ending food intake 3+ hours before sleep.

Why

The metabolic switch from glucose to ketone metabolism occurs at 12–16 hours of fasting, when hepatic glycogen depletes and AMPK activates.[5] The Bensalem 2025 RCT used a self-selected 10-hour eating window (14-hour fast) and measured significantly higher autophagic flux versus standard care at 6 months.[4] Wilkinson et al. (2020) demonstrated cardiometabolic improvements with a 10-hour TRE window in metabolic syndrome patients.[17]

14–16 Establish a consistent 14–16 hour daily fast (10-hour eating window), ending foo
Common mistake

Assuming longer is always better. Prolonged multi-day fasts carry bone fragility and muscle catabolism risks that 14–16 hour daily fasts do not.[21]

02 Step 02 · Within window

Protein Protection

Consume adequate protein (≥1.2 g/kg/day) within the eating window to prevent muscle catabolism.

Why

Fazeli and Steinhauser (2025) explicitly flag sarcopenia risk with protein-insufficient fasting protocols.[21] Adequate protein within the eating window maintains muscle protein synthesis while allowing autophagic clearance during the fasting period.

1.2 Consume adequate protein (≥1.2 g/kg/day) within the eating window to prevent mus
Common mistake

Eliminating protein to "extend fasting effects." The science supports fasting duration, not chronic protein restriction, the two are independent variables.

03 Step 03 · Within window

Resistance Training

Perform structured resistance training within the eating window for combined effects on body composition.

Why

TRE combined with structured exercise training produced consistent small reductions in fat mass (ES = −0.20) and body fat percentage (ES = −0.23) across included trials in a 2024 systematic review and meta-analysis.[42] Exercise independently activates mitophagy and autophagic quality control in skeletal muscle.[39]

Perform structured resistance training within the eating window for combined eff
Common mistake

Training fasted for "extra autophagy." The evidence supports training within the eating window, nutrient availability during and after resistance exercise supports muscle adaptation.

04 Step 04 · Weekly

Periodic Deeper Fasts

Add 1–2 extended fasts per week (24 hours or 5:2 protocol: 500 kcal on 2 non-consecutive days) for deeper autophagy induction.

Why

Mattson et al. (2024) used a 5:2 protocol and demonstrated measurable brain imaging changes in 8 weeks.[15] The 5:2 approach creates periodic deeper energy deficits that push beyond the daily fasting threshold, potentially activating autophagy in tissues that require longer fasting signals.[5]

1–2 Add 1–2 extended fasts per week (24 hours or 5:2 protocol: 500 kcal on 2 non-con
Common mistake

Combining daily TRE with weekly extended fasts without adequate recovery. The protocols are additive, start with daily TRE, add periodic fasts only after adaptation.

06Verdict

The verdict.

Bottom line

Your cells already know how to recycle. The question is whether your eating schedule lets them.

The autophagy fasting science that has emerged over the past fifteen years, from Kim's molecular switch in 2011, through Ohsumi's Nobel Prize in 2016, to the first human autophagy RCT in 2025, establishes a fundamental reframing of what fasting does. It is not primarily a weight-loss strategy, a calorie-management tool, or a willpower exercise. It is the metabolic condition under which cells activ

The whole argument, on one axis

The brain's fuel shift, measured directly.

0 0.3 0.6 0.9 1.2 brain beta-hydroxybutyrate (mmol/L) 3-DAY FAST · 4T MRS · PAN ET AL. 2000 0.98 mmol/L FED STATE · BELOW MRS DETECTION LIMIT below 0.1 mmol/L
01Claim

The Recycling Switch

Fasting activates a molecular competition at ULK1, AMPK versus mTOR, that controls whether cells build or recycle. The switch has a measurable threshold at 12–16 hours, after which autophagic flux increases in both animal models and, as of 2025, in controlled human trials.

Claim
02Consequence

The Cost of Constant Feeding

A body that never crosses the fasting threshold is a body whose cells never fully activate their quality-control system. The consequences accumulate in four systems, brain, liver, heart, and muscle, each of which shows measurable autophagy impairment in chronic overfeeding and aging.

Consequence
03Lever

The Daily Window

Extending the overnight fast to 14–16 hours reliably crosses the metabolic switch threshold. This is not an extreme intervention, it is a return to a feeding pattern that, until the industrialization of food, was the human default.

meta-analysis

Editorial confidence

Low
Medium
Moderate-High

48 sources · Robust mechanistic foundation (replicated molecular switch) · first-generation controlled human trials (2024–2025) · converging evidence across species and measurement methods · human evidence early-stage but directionally consistent

,  30 ,

07Bibliography

48 sources · ~6h est. corpus read · 48 visible

Meta · 1 Review · 5 Cohort · 1 Journal · 41
Type
Sort
  1. 01 Journal

    Kim, J., Kundu, M., Viollet, B., & Guan, K. L2011

    AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

    Nature Cell Biology132–141

  2. 02 Journal

    Mizushima, N., & Komatsu, M2011

    Autophagy: Renovation of cells and tissues

    Cell728–741

  3. 03 Journal

    Rubinsztein, D. C., Mariño, G., & Kroemer, G2011

    Autophagy and aging

    Cell682–695

  4. 04 Journal

    Bensalem, J., Teong, X. T., Hattersley, K. J., Hein, L. K., Fourrier, C., Dang, L. V. P., Singh, S., Liu, K., Wittert, G. A., Hutchison, A. T., Heilbronn, L. K., & Sargeant, T. J2025

    Intermittent time-restricted eating may increase autophagic flux in humans: An exploratory analysis

    Journal of Physiology3019–3032

  5. 05 Journal

    de Cabo, R., & Mattson, M. P2019

    Effects of intermittent fasting on health, aging, and disease

    New England Journal of Medicine2541–2551

  6. 06 Journal

    Nikoletopoulou, V., Sidiropoulou, K., Kallergi, E., Dalezios, Y., & Tavernarakis, N2017

    Modulation of autophagy by BDNF underlies synaptic plasticity

    Cell Metabolism230–242

  7. 07 Journal

    Levine, B., & Kroemer, G2019

    Biological functions of autophagy genes: A disease perspective

    Cell1–2

  8. 08 Journal

    Mattson, M. P., Longo, V. D., & Harvie, M2017

    Impact of intermittent fasting on health and disease processes

    Ageing Research Reviews46–58

  9. 09 Journal

    Longo, V. D., & Panda, S2016

    Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan

    Cell Metabolism1048–1059

  10. 10 Journal

    Eisenberg, T., Abdellatif, M., Schroeder, S., et al2016

    Cardioprotection and lifespan extension by the natural polyamine spermidine

    Nature Medicine1428–1438

  11. 11 Journal

    Pan, J. W., Rothman, D. L., Behar, K. L., Stein, D. T., & Hetherington, H. P2000

    Human brain β-hydroxybutyrate and lactate increase in fasting-induced ketosis

    Journal of Cerebral Blood Flow and Metabolism1502–1507

  12. 12 Journal

    Aman, Y., Schmauck-Medina, T., Hansen, M., et al2021

    Autophagy in healthy aging and disease

    Nature Aging634–650

  13. 13 Journal

    Alirezaei, M., Kemball, C. C., Flynn, C. T., Wood, M. R., Whitton, J. L., & Kiosses, W. B2010

    Short-term fasting induces profound neuronal autophagy

    Autophagy702–710

  14. 14 Journal

    Morselli, E., Maiuri, M. C., Markaki, M., et al2010

    Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy

    Cell Death & Disease

  15. 15 Journal

    Mattson, M. P., et al2024

    Brain responses to intermittent fasting and the healthy living diet in older adults

    Cell Metabolism

  16. 16 Journal

    Jakubek, P., Pakula, B., Rossmeisl, M., et al2024

    Autophagy alterations in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease: The evidence from human studies

    Internal and Emergency Medicine1739-024

  17. 17 Journal

    Wilkinson, M. J., Manoogian, E. N. C., Zadourian, A., et al2020

    Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome

    Cell Metabolism92–104

  18. 18 Journal

    Ntsapi, C., & Loos, B2016

    Caloric restriction and the precision-control of autophagy: A strategy for delaying neurodegenerative disease progression

    Ageing Research Reviews32–45

  19. 19 Journal

    NCD Risk Factor Collaboration2024

    Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

    Lancet6736(23) · 1027–1058

  20. 20 Journal

    Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G2019

    Caloric restriction mimetics against age-associated disease: Targets, mechanisms, and therapeutic potential

    Cell Metabolism592–610

  21. 21 Journal

    Fazeli, P. K., & Steinhauser, M. L2025

    A critical assessment of fasting to promote metabolic health and longevity

    Endocrine Reviews856–876

  22. 22 Journal

    Babygirija, R., Han, J. H., Sonsalla, M. M., Matoska, R., Calubag, M. F., Green, C. L., Tobon, A., Yeh, C. Y., Vertein, D., Schlorf, S., Illiano, J., Liu, Y., Grunow, I., Rigby, M. J., Puglielli, L., Harris, D. A., Denu, J. M., & Lamming, D. W2025

    Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer's disease

    Nature Communications1467-025

  23. 23 Review

    Bagherniya, M., Butler, A. E., Barreto, G. E., & Sahebkar, A2018

    The effect of fasting or calorie restriction on autophagy induction: A review of the literature

    Ageing Research Reviews183–197

  24. 24 Journal

    Glick, D., Barth, S., & Macleod, K. F2010

    Autophagy: Cellular and molecular mechanisms

    Journal of Pathology3–12

  25. 25 Journal

    Levine, B., & Kroemer, G2008

    Autophagy in the pathogenesis of disease

    Cell27–42

  26. 26 Journal

    0

    Molecular mechanisms of autophagy in yeast

  27. 27 Journal

    Hofer, S. J., Daskalaki, I., Bergmann, M., Friščić, J., Zimmermann, A., Mueller, M. I., Abdellatif, M., Nicastro, R., Masser, S., Durand, S., Nartey, A., Waltenstorfer, M., Enzenhofer, S., Faimann, I., Gschiel, V., Bajaj, T., Niemeyer, C., Gkikas, I., Pein, L., Cerrato, G., Pan, H., Liang, Y., Tadic, J., Jerkovic, A., Aprahamian, F., Robbins, C. E., Nirmalathasan, N., Habisch, H., Annerer, E., Dethloff, F., Stumpe, M., Grundler, F., Wilhelmi de Toledo, F., Heinz, D. E., Koppold, D. A., Rajput Khokhar, A., Michalsen, A., Tripolt, N. J., Sourij, H., Pieber, T. R., de Cabo, R., McCormick, M. A., Magnes, C., Kepp, O., Dengjel, J., Sigrist, S. J., Gassen, N. C., Sedej, S., Madl, T., De Virgilio, C., Stelzl, U., Hoffmann, M. H., Eisenberg, T., Tavernarakis, N., Kroemer, G., & Madeo, F2024

    Spermidine is essential for fasting-mediated autophagy and longevity

    Nature Cell Biology1556-024

  28. 28 Journal

    Rubinsztein, D. C., Bjedov, I., et al2018

    Autophagy and the cell biology of age-related disease

    Nature Cell Biology1361–1374

  29. 29 Journal

    Hansen, M., Rubinsztein, D. C., & Walker, D. W2018

    Autophagy as a promoter of longevity: Insights from model organisms

    Nature Reviews Molecular Cell Biology579–593

  30. 30 Journal

    [Multiple authors]2017

    Autophagy in neurodegenerative diseases: Pathogenesis and therapy

    PMC5739982

  31. 31 Journal

    Egan, D. F., Shackelford, D. B., Mihaylova, M. M., et al2011

    Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy

    Science456–461

  32. 32 Journal

    Alers, S., Löffler, A. S., Wesselborg, S., & Stork, B2012

    Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: Cross talk, shortcuts, and feedbacks

    Molecular and Cellular Biology2–11

  33. 33 Cohort

    Bou Malhab, L. J., Madkour, M. I., Abdelrahim, D. N., Eldohaji, L., Saber-Ayad, M., Eid, N., Abdel-Rahman, W. M., & Faris, M. E2024

    Dawn-to-dusk intermittent fasting is associated with overexpression of autophagy genes: A prospective study on overweight and obese cohort

    Clinical Nutrition ESPEN

  34. 34 Journal

    Jafari, M., Macho-González, A., Diaz, A., Lindenau, K., Santiago-Fernández, O., Zeng, M., Massey, A. C., de Cabo, R., Kaushik, S., & Cuervo, A. M2024

    Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy

    PNAS

  35. 35 Journal

    Triolo, M., & Hood, D. A2021

    Manifestations of age on autophagy, mitophagy and lysosomes in skeletal muscle

    Cells

  36. 36 Journal

    Palmer, J. E., Wilson, N., Son, S. M., Obrocki, P., Wrobel, L., Rob, M., Takla, M., Korolchuk, V. I., & Rubinsztein, D. C2024

    Autophagy, aging, and age-related neurodegeneration

    Neuron6273(24) · 0896-6273

  37. 37 Journal

    Tumurbaatar, I., et al2023

    Preserved autophagy in cognitively intact non-demented individuals with Alzheimer's neuropathology

    Alzheimer's & Dementia

  38. 38 Journal

    Triolo, M., & Hood, D. A2021

    Manifestations of age on autophagy, mitophagy and lysosomes in skeletal muscle

    Cells

  39. 39 Review

    Mehrabani, S., Bagherniya, M., Askari, G., Read, M. I., & Sahebkar, A2020

    The effect of fasting or calorie restriction on mitophagy induction: A literature review

    Ageing Research Reviews

  40. 40 Journal

    Parvaresh, H., Paczek, K., Al-Bari, M. A. A., & Eid, N2024

    Mechanistic insights into fasting-induced autophagy in the aging heart. PMC10989221.

  41. 41 Journal

    Singh, I., Bhat, S., Tamatta, R., & Singh, A. K2026

    Interplay between autophagy, cellular senescence, and brain aging: Neuroprotective implications of intermittent fasting

    Cellular and Molecular Neurobiology0571-026

  42. 42 Meta

    Hays, H. M., Sefidmooye Azar, P., Kang, M., Tinsley, G. M., & Wijayatunga, N. N2024

    Effects of time-restricted eating with exercise on body composition in adults: A systematic review and meta-analysis

    International Journal of Obesity1366-024

  43. 43 Review

    Sun, M. L., Yao, W., Wang, X. Y., Gao, S., Varady, K. A., Forslund, S. K., Zhang, M., Shi, Z. Y., Cao, F., Zou, B. J., Sun, M. H., Liu, K. X., Bao, Q., Xu, J., Qin, X., Xiao, Q., Wu, L., Zhao, Y. H., Zhang, D. Y., Wu, Q. J., & Gong, T. T2024

    Umbrella review: Intermittent fasting and health outcomes

    eClinicalMedicine (The Lancet)

  44. 44 Review

    [Multiple authors]2023

    Neurotrophic effects of intermittent fasting, calorie restriction and exercise: A review and annotated bibliography

    Frontiers in Aging

  45. 45 Journal

    Beveridge, J., Montgomery, A., & Grossberg, G2025

    Intermittent fasting and neurocognitive disorders: What the evidence shows

    Journal of the Neurological Sciences

  46. 46 Journal

    Shabkhizan, R., Haiaty, S., Moslehian, M. S., Bazmani, A., Sadeghsoltani, F., Saghaei Bagheri, H., Rahbarghazi, R., & Sakhinia, E2023

    The beneficial and adverse effects of autophagic response to caloric restriction and fasting

    Nutrients

  47. 47 Journal

    Dastghaib, S., Siri, M., Rahmani-Kukia, N., Heydari, S. T., Pasalar, M., Zamani, M., Mokaram, P., & Bagheri-Lankarani, K2025

    Effect of 30-day Ramadan fasting on autophagy pathway and metabolic health outcome in healthy individuals. PMC11865935.

  48. 48 Review

    Vergara Nieto, Á. A., Diaz, A. H., Hernández, M., & Sagredo, D2025

    A narrative review about metabolic pathways, molecular mechanisms and clinical implications of intermittent fasting as autophagy promotor. PubMed 40481380. ---

Keep reading

More from the Science Deep Dives

High-Performance Insights

Leave a Reply

Your email address will not be published. Required fields are marked *