⏱️ Autophagy Activation Threshold Simulator

Fed State — mTOR Dominant, Autophagy Off

Nutrients keep mTOR active and autophagy locked down.

• 0h: Fasting Hours (meal just finished)
• 92%: mTOR Activity (growth signaling on)
• 8%: AMPK Activity (energy sensor quiet)
• 3%: Autophagy Level (baseline housekeeping only)

mTORC1 suppresses autophagy initiation

Amino acids and insulin keep mTORC1 fully active.

Active mTORC1 phosphorylates ULK1, blocking the initiation complex.

Fed mTOR directly blocks the ULK1 autophagy switch.

Glycogen fuels early energy needs

Liver glycogen covers energy demand right after meals.

No AMPK stress signal is generated yet.

Baseline autophagy still runs

A small constitutive flux clears damaged organelles.

This floor stays active even in the fed state.

12 Hours — Early AMPK Activation Begins

Glycogen depletes and AMPK starts to stir.

• 12h: Fasting Hours (glycogen running low)
• 75%: mTOR Activity (still largely active)
• 25%: AMPK Activity (first stirrings)
• 15%: Autophagy Level (small step up)

Glycogen stores near exhaustion

Liver glycogen reserves fall close to empty.

Blood glucose starts drifting lower.

AMPK senses rising AMP:ATP ratio

Falling ATP nudges AMPK toward activation.

This is the first measurable metabolic shift.

12h marks the first detectable AMPK signal rise.

Autophagy ticks up slightly

Autophagosome formation increases only modestly.

mTOR still restrains most of the machinery.

16 Hours — mTOR Suppression Grows

The mTOR brake loosens as AMPK gains ground.

• 16h: Fasting Hours (time-restricted eating range)
• 55%: mTOR Activity (declining fast)
• 45%: AMPK Activity (clearly active)
• 38%: Autophagy Level (visible rise)

AMPK phosphorylates TSC2 and Raptor

AMPK directly inhibits mTORC1 at two points.

This is the classic 16:8 fasting window.

16h is where popular time-restricted eating lands.

ULK1 complex starts freeing up

Reduced mTORC1 phosphorylation releases ULK1.

Initiation complex assembly becomes possible.

Ketone production begins rising

Fat-derived ketones start supplementing glucose.

This further signals a fasted metabolic state.

24 Hours — Strong AMPK/mTOR Shift

A full day fasted flips the switch decisively.

• 24h: Fasting Hours (one full day)
• 30%: mTOR Activity (strongly suppressed)
• 70%: AMPK Activity (dominant signal)
• 72%: Autophagy Level (substantial activation)

ULK1 complex fully activates

Low mTORC1 lets ULK1 phosphorylate Beclin-1.

Phagophore nucleation ramps up broadly.

24h fasting produces a clear step-change in flux.

Autophagosome numbers climb sharply

Cells show a marked jump in vesicle count.

Damaged proteins and organelles get tagged fast.

Systemic stress-response genes engage

FOXO3 and related transcription factors activate.

Autophagy gene expression rises broadly.

48 Hours — Maximal Activation Plateau

Extended fasting reaches peak autophagy activation.

• 48h: Fasting Hours (extended fast)
• 8%: mTOR Activity (near fully off)
• 92%: AMPK Activity (near maximal)
• 97%: Autophagy Level (peak activation)

Autophagy flux plateaus near maximum

Further fasting yields diminishing extra activation.

The system has reached a functional ceiling.

48h is the practical ceiling for fasting-driven activation.

Lysosomal biogenesis keeps pace

TFEB activation expands degradation capacity.

This supports the sustained autophagosome load.

Refeeding rapidly reverses the state

A single meal restores mTOR within hours.

The threshold system resets quickly after eating.