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

Mimicking Hibernation And Preserving Organs

 
hibernate sleep.jpg
 

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

Contents:

  1. What Are Hibernation Induction Triggers?
  2. What Defines A Hibernation Mimetic?
  3. Benefits Of Hibernation Mimetics
  4. List Of Hibernation Mimetics
  5. Mechanism Of Action

What Are Hibernation Induction Triggers?

 
 https://www.researchgate.net/profile/Michal_Heger2/publication/297453156_The_physiology_of_artificial_hibernation/links/594f7a8ca6fdccebfa69e435/The-physiology-of-artificial-hibernation.pdf

https://www.researchgate.net/profile/Michal_Heger2/publication/297453156_The_physiology_of_artificial_hibernation/links/594f7a8ca6fdccebfa69e435/The-physiology-of-artificial-hibernation.pdf

 

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

What Defines A Hibernation Mimetic?

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

Benefits Of Hibernation Mimetics

 
 https://link.springer.com/book/10.1007%2F978-3-319-25495-1

https://link.springer.com/book/10.1007%2F978-3-319-25495-1

 

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

List Of Hibernation Mimetics

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

Mechanism Of Action

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