to g or not to g: that is the questionto g or not to g: that is the question. protein synthesis –...

TO G OR NOT TO G: THAT IS THE QUESTION

VINCENT J. CAIOZZO, PH.D.1,2

and

Kenneth M. Baldwin, PH.D.2

1Departments of Orthopaedics

and2Physiology and Biophysics

School of MedicineUniversity of California

Irvine, CA


Accomplishments of the US Space Program havebeen …

Out of this world

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiMko7qzenZAhVCh1QKHZWVDgwQjRwIBg&url=http%3A%2F%2Faerospacelegacyfoundation.com%2Fgemini-program%2F&psig=AOvVaw02Ll-SuXplNX9XDXh57OXu&ust=1521041061228691


https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiQv_CE0OnZAhXIzFQKHf4MCtoQjRwIBg&url=https%3A%2F%2Fwww.space.com%2F18162-space-shuttle-atlantis.html&psig=AOvVaw3dx-vu8PX6BGVBIr31b9i5&ust=1521041607854525https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjzqIGj0OnZAhWhs1QKHX2vCiMQjRwIBg&url=https%3A%2F%2Fwww.theverge.com%2F2018%2F1%2F24%2F16930154%2Fnasa-international-space-station-president-trump-budget-request-2025&psig=AOvVaw0VKOVWJ5DmAB7BtwkwmTd4&ust=1521041756248859


SO MANY GREAT IMAGES OF SPACE EXPLORATION

But there is one singularimage that best capturesthe achievement of the space program…

Man’s desire to explore

50 years ago comeJuly 20, 2019

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiMscLW0unZAhUqllQKHQLcCDoQjRwIBg&url=https%3A%2F%2Fmilnersblog.com%2Ftag%2Ffamily-of-neil-armstrong-quote%2F&psig=AOvVaw0AYwD382ozbISShlG9rmh-&ust=1521042402135505


THE JOURNEY FROM EARTH TO MARS WILL BE EQUALLYHISTORICAL

“We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard.”

But the challenges will be profoundly greater!

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwietaH56-zZAhVH9WMKHaYRBFAQjRwIBg&url=https%3A%2F%2Fsolarsystem.nasa.gov%2Fplanets%2Fmars%2Foverview%2F&psig=AOvVaw1f4QSwkh279OWapZ8rVxqB&ust=1521152220631939


“Men wanted for hazardousjourney. Small wages, bitter cold, long months of complete darkness, constant danger, safe return doubtful. Honour and recognition in case of success.”

Sir Ernest Henry Shackleton


Exploration even within the solar system poses unique and formidable challenges never experienced during human evolution!

space radiation vacuum and cold of space staggering distances and

time the absence of gravity


Profound PhysiologicalDeconditioning/Alterations

o Vestibular Systemo Cardiovascular Systemo Skeletal Systemo Muscleo Intracranial Hypertension

SPACE FITNESS: NEWTON’S FOURTH LAW

Three Laws of Motion

First Law – Uniform motionSecond Law – F = MAThird Law – Action-reaction

So what is the Fourth Law?

It is the law of physiologicalplasticity and is analogousto the Third Law.

Look at a couple of exampleswith direct relevance tospace flight

Adams, Caiozzo, and Baldwin 2003

LeBlanc et al. 1996-2 -1.5 -1 -0.5 0

NeckSpine

Arm

PelvisTroch

Leg

∆ BMD per month (%)

Bone Loss on MIR

Post Menopausal Bone Loss per month


Lang et al. 2004-1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0BMD Loss per month

ISS (n = 14)

MIR (n = 18)

Lumbar Spine

Femoral Neck

Calcaneus

-1.4 -1.0 -0.6 -0.2 0


Bone Loss on MIR

ESA astronaut Jean-Pierre Haigneré returning to Earth after a six month stay on board the Russian space station Mir. (Kazakhstan, August 1999).

Hamlet – Scene I“To be, or not to be: that is the question”

How does that apply to the topic of this presentation?

“To G, or not to G: that is the question”


http://www.google.com/url?sa=i&source=images&cd=&cad=rja&docid=WmObhZF6pc30UM&tbnid=2Dk06tr82bzukM:&ved=0CAgQjRwwAA&url=http%3A%2F%2Fgreatewhitenorth.blogspot.com%2F2013%2F01%2Fscrutinizing-shakespeare.html&ei=uxs9UpGEAcWSqwGi5IGACw&psig=AFQjCNF1sYZzDBDhqr1X2LeqfWNiOLYMfg&ust=1379822907117758

WHY SHOULD WE BE INTERESTED IN THIS TOPIC?

The Space Cycle Unique Attributes

oLoad skeletal muscleoLoad boneoProvide gravitational challenge

to cardiovascular systemoVestibular challengeoMay be effective in mitigating

intracranial hypertension


STRATEGIES FOR LOADING MUSCLE AND BONE:HYPERGRAVITY RESISTANCE TRAINING


Hypergravity Resistance Training Hypotheses

AG can be used to create hypergravity-loading conditions that result in muscle adaptations similar to those seen when performing resistance training in a normal 1 G environment.



Proof-of-Principle Study Design

MOLECULAR MARKERS OF HYPERTROPHY/ATROPHY

TYPES AND AMOUNTS OF PROTEIN

CELLULAR FUNCTION

MUSCLE FUNCTION

ORGANISM

TORQUE-VELOCITY RELATIONSHIP

MRI IMAGING MUSCLE FIBER AREA

MHC PROTEIN ISOFORMS Actin mRNA

MHC mRNA isoforms IGF-1 mRNA, MGF mRNA, p70s6k

10 RM SQUAT


Molecules-to-Function Paradigm:A Play on Structure-Function Relationships

Actin mRNA

MHC mRNA isoforms

IGF-1 mRNA, MGF mRNA, p70s6k

MRI IMAGING

MUSCLE FIBER AREA

MHC PROTEIN ISOFORMS

TORQUE-VELOCITY

RELATIONSHIP

10 RM SQUAT

MOLECULAR MARKERS OF

HYPERTROPHY/ATROPHY

ORGANISM

MUSCLE FUNCTION

CELLULAR FUNCTION

TYPES AND AMOUNTS OF PROTEIN


Muscle Strength


Protein Synthesis – Total RNA

Note that both groups had significantincreases in total RNA.

Also, note that the increases for bothGroups were very similar.


Protein Synthesis – Translational Control

RT1 RT2 HGRT2HGRT1

pre post pre post pre postpre post

0 4 24 0 4 24 0 4 24 0 4 24 0 4 24 0 4 240 4 0 4 24

pp85S6Kpp85S6Kpp70S6K

RT1 RT2 HGRT2HGRT1

pre post pre post pre postpre postpre post pre post pre postpre post

0 4 24 0 4 24 0 4 24 0 4 24 0 4 24 0 4 240 4 0 4 240 4 24 0 4 24 0 4 24 0 4 240 4 24 0 4 24 0 4 24 0 4 24 0 4 24 0 4 240 4 0 4 24

pp85S6Kpp85S6Kpp70S6Kpp85S6Kpp85S6Kpp70S6K

-4 0 4 8 12 16 20 240

100

200

300

400

500

600prepost

Hours post bout

pp85

in S

C (n

=4)

AU

/uni

t pro

tein

-4 0 4 8 12 16 20 240

100

200

300

400

500

600

700prepost

Hours post bout

pp85

in F

W (n

=4)

AU

/uni

t pro

tein

-4 0 4 8 12 16 20 240

100

200

300

400

500

600prepost

Hours post bout

pp85

in S

C (n

=4)

AU

/uni

t pro

tein

-4 0 4 8 12 16 20 240

100

200

300

400

500

600

700prepost

Hours post bout

pp85

in F

W (n

=4)

AU

/uni

t pro

tein


Molecular Marker of Muscle Hypertrophy

Note similarity in acute responses.

Note that both typesof resistance trainingprograms producedsimilar chronic elevation.


Molecular Marker of Extracellular Matrix Remodeling

Note similarity in acute responses.

Note that both typesof resistance trainingprograms producedsimilar chronic elevation.

Where Do We Go From Here?


So in taking Mother Earth to Mars,can we forget about taking Earth’sgravitational environment?

We need to answer thisfundamental question!

Consider that Earth’s gravitationalfield was probably one of the most important evolutionarypressures!

.



Artificial gravity has the potential tomimic Earth’s gravitational fieldand load every element of thehuman body, which is not possible with other countermeasure devices.

Simply stated, artificial gravitycan provide Earth-likechallenges to muscle, skeletal, cardiovascular, and vestibularsystems during a single sessionsomething that no other countermeasurecan achieve.



Need a sustained gravitational biology program that addresses thisfundamental question if we are toensure the health and safetyof our astronauts.

Data clearly demonstrate that hypergravity resistance training produces adaptations very similarto 1g squat resistance training.

Good initial set of data that shouldstimulate additional studies onthe effectiveness of artificial gravity.

FUNDING

National Aeronautical Space Administration (NASA)Hypergravity Resistance Training: Countermeasure to Microgravity

MA00403 2004-2008

National Institutes of HealthU.C. Irvine General Clinical Research Center

GCRC MO1RR00827-S1 2000-2005


RESEARCH TEAM

Vincent J. Caiozzo, PH.D.Kenneth M. Baldwin, Ph.D.

Greg Adams, Ph.D.Fadia Haddad, Ph.D.

Jim Hicks, Ph.D.Jim Earthman, Ph.D.

Dan Cooper, M.D.Art Kreitenberg, M.D.Alan Hargens, Ph.D.

Peter Cavanagh, Ph.D.

ACADEMIC UNITS

UniversitiesUniversity of California, Irvine

University of California, San DiegoUniversity of Washington

DepartmentsOrthopaedics

Physiology and BiophysicsEcology and Evolutionary Biology

PediatricsChemical Engineering & Materials Science

Biomedical Engineering


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to g or not to g: that is the questionto g or not to g: that is the question. protein synthesis –...

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