Torpor And Hibernation Mimetics: Hibernation Induction Triggers, DADLE, and Deltorphins

Hibernation induction trigger (HIT) is a hormone that binds to delta-opioid receptors and has the ability to protect tissues from death, oxygen loss, and more. R

HIT may be beneficial for preserving muscle in those who are bedridden and may be useful for astronauts who are weightless. R

Torpor is a physiological state characterized by controlled lowering of metabolic rate and core body temperature, allowing substantial energy savings during periods of reduced food availability or harsh environmental conditions. R

Hibernation is a biological strategy used to tolerate stress of depleted energy stores, intracellular acidosis, hypoxia, hypothermia, cell volume shifts, and inactivity induced muscle wasting. R

Hibernation Induction Trigger (HIT) is a hormone trigger that activates hibernation's protective mechanisms, may be an intervention for multiple stresses including environmental toxins, disease states, trauma, and aging. 

In animals, HIT is able to enact hibernation/torpor, while in humans it appears to enhance survival of tissues and organs. R

Hibernation Mimetics should:

1. Preserve Energy Stores by torpor - depressed metabolism and reduced body temperature R R
2. Bind to delta 2 opioid receptors R

In real life examples, hibernation mimetics should help cold, hunger, and loss of blood oxygen/glucose to cells.

Some other benefits of hibernation mimetics may be:

1. Accelerates the healing of injuries R
2. Increases the life span of donor organs R R
3. Protects muscles from hypoxia/reperfusion injury R
4. Protects the brain (via hormesis) from toxins, ischemic stroke, and hemorrhagic stroke R R
5. Protects the heart from cardiac ischemia R R R

• DOR2 agonists (DADLE and Deltorphins) R
• Thioredoxin-interacting protein (Txnip) R 
• 3-Iodothyronamine (T1AM) R

Some Genes HIT Should Regulate:

• Increase HIF-1alpha R
• Increase PGC-1 R
• Increase PPAR-gamma R

The delta 2 opioid receptors, DADLE and Deltorphins are mimetics of HIT and here are some of their benefits.

DADLE

DADLE (D-Ala2-D-Leu5 enkephalin):

• Activates the beneficial recompensatory phase R
• Ameliorates neuronal damage induced by ischemia-reperfusion R
• Induces hibernation in hela cells R
• Protects against neurotoxins (protects dopaminergic system from methamphetamine use) R

Deltorphins

Deltorphin D (Delt D):

• Facilitates recovery from moderate (~30%) hemorrhage after blood pressure crash R
• Has anti-inflammatory activity: Suppress LPS-induced p38 MAPK, TNFalpha. and MIP-2 R
• Induces tolerance to cardiac ischemia (via PKC, NOS, KATP channels, and the autonomic nervous system) R

Deltorphin E (Delt E):

• Protects from ischemic shock R
• Reduces lactic acid acidosis R
• Restores hemodynamic stability after severe hemorrhage (~50%) treatment R