This presentation is originally from 2006, but is still very relevant today. You can contact me with questions here: http://www.drhectorlopez.com/

1. Sarcopenia: Exercise,
Nutrition and Beyond
Hector Lopez, MD, CSCS, MS(c)
Physical Medicine and Rehabilitation
RIC-Rehabilitation Institute of Chicago
Northwestern University School of Medicine
Co-Founder: Physicians Pioneering Performance, LLC
Northeast Spine and Sports Medicine, PC.

2. Outline
 Definition/ Epidemiology/ Scope
 What’s in a name?
 “Players”/ Contributing factors
 Intrinsic Muscle cellular/Molecular
signaling/
 Neuromuscular changes
 Cytokine/ Immunologic
 Endocrine/ Metabolic (Systemic/ Cell)
 Nutritional (Anorexia/Extrinsic and
Responsiveness/Intrinsic)
 Oxidative Stress
 Physical Activity (Bidirectional-
Perpetual Cycle)
 Atherosclerosis/ PVD
 Partial Role of Apoptosis?

3. Outline (cont.)
 Cachexia/Wasting vs. Sarcopenia of
Aging
 Role of Supplements/Nutritional
Strategies
 Exercise Strategies
 Pharmacologic Adjuncts
 On the Horizon

5. Sarcopenia
 Age-related, involuntary loss of muscle
mass, strength and function
 3-8% loss of muscle mass per decade
after 30, steeper after 60
 Sarcopenia + Obesity = “fat-frail”
 Fundamental cause of disability,
functional dependence, falls, worsening
outcome from other illness/disease
[Baumgartner RN et al. 1999; Morley JE et al. 2001]

6. Sarcopenia
 Prevalence: 35% - 45% of Older US
population (>65)
 Modifiable public health care cost/
burden – over $60 billion and escalating
with senior demographic [Janssen I et al. 2004]
 DEXA and RSMI for estimating
prevalence [Wang Z et al. 1996; Proctor DN et al. 1999]
 Solution to this problem: Multi-
disciplinary approach vis a vis
Performance Nutrition/ Fitness
Professionals

7. What’s in a name?
 Sarcopenia a misnomer?
 “Sarco” (G. sarx = flesh)
 “Penia” (G. penia = poverty/
deficiency)
 “Myo” (G. myos = muscle)
 I propose “Myopenia”

8. “Players” in Sarcopenia
 Intrinsic Muscle (Molecular and Cellular)
 Reduced muscle cell #, SRetic volume Ca++
handling
 Myonuclear centralization, reduced plasma
membrane potential/sensitivity, intra-myocellular
 Age-related decline in basal/resting MHC, and
mixed muscle protein synthesis
 Disproportionate atrophy of type IIA muscle fibers
 ↓ IGF-1/PI3K/Akt signalling ↑FOXO(forkhead
fam TFs), MAFbx/Atrogin (muscle atrogin F-box
containing ubiquitin ligase) and MuRF1 (muscle ring
finger ub-ligase)
 ↓Satellite Cell activation/ signaling for
differentiation, recruitment and proliferation (less
MHC and CK expression)

9. “Players” in Sarcopenia
 Neuromuscular
 Decreased in distal more than
proximal MU populations
 ↓ # and NCV of α-motor neurons (esp.
the larger, faster conducting FF and FFR type)
 ↓ Rate firing, Rate coding
 ↑ Peripheral sprouting (more distal)
 ↓ Neuromusc End-plate area/ folds
 Cytokine/ Immunologic
 Still many gaps in our knowledge 
do know altered cytokine “milieu” w/
aging;
 small change in protein catabolism/
anabolism balance X many years =
large BComp change

10. “Players” in Sarcopenia
 Cytokine/ Immunologic (cont.)
 ↑ tIL-6, IL-1R, systemic TNF, possible
relative inc tIL-1 [Roubenoff R et al. 1998]
 IL-6 is moderate catabolic cytokine, also
functions as regulator of TNF and IL-1R
 IL-6 suppresses extensive inflammation in
elderly AT the EXPENSE of ….skel
muscle proteolysis, AA oxidation/
mobilization
 Cytokines confer a “permissive” effect to
‘foster’ sarcopenia with low-grade
systemic inflammation as a catabolic
backdrop for –’ve muscle protein balance

11. “Players” in Sarcopenia
 Endocrine/Metabolic
 Cellular:
 ↓Glycogenolytic, Glycolytic capcity,
Phosphagen circuit (↓ATP, CrP),
TCA cycle enzymes, Mitochondrial
Resp Chain Fxn/ mtDNA and mt-
protein synth  VO2max decrement
 Altered protein metabolism (basal
MHC and sarcoplasmic protein
synthesis, and mt-Protein synthesis)

12. “Players” in Sarcopenia
 Endocrine/Metabolic
 Systemic:
 Testosterone- 60% over age of 65
are hypogonadal (Andropause)
 ↓DHEA- (Adrenopause)
 GH/ IGF-1 axis- gradual decline w/
aging [Lamberts SW et al. 1997]
 ↓ Autocrine/ Paracrine MGF/ FGF/
PDGF peptide growth factors
 Insulin Resistance at Skeletal
Muscle (blunted downstream signaling for
protein synthesis in elderly  vast diff in
anabolic response to mixed meals young
vs. elders) [Rasmussen BB et al. 2006]

13. “Players” in Sarcopenia
 Nutritional/ Intrinsic
 Endogenous whole body and muscle
protein response to carb-protein
(mixed meal feeding) is perturbed:
• Insulin appears to abrogate and impair
anabolic response of muscle protein to
the + effect of AA alone [Dreyer H et al. 2005;
Volpi et al. 2000; Rasmussen et al. 2006]
 ↓GH pulse magnitude in post-
absorptive state

14. “Players” in Sarcopenia
 Nutritional/ Extrinsic
 Anorexia of aging: food intake
requires complex integration of Periph
and Central signals
 ↓ fundal relaxation of stomach
 ↑ antral stretch of stomach
 ↑ CCK release to given fat load
 Leptin increases in ♂ throughout
lifespan; in ♀ decline in old age
 Anorectic cytokines (CilNF, TNF,
etc.)
 Central regulation-neurotransmitters,
endogenous opioids, NPY, endo-
cannabinoid/ vanilloid systems
 Cross-talk in neurochemistry with
Mood

15. “Players” in Sarcopenia
 Oxidative Stress (particularly mt fxn)
 ROS/RNS generated in muscle  oxidative
stress
 Metabolic stressors (Steady state and
Exercise), inflammatory stressors, co-existing
disease
 ~65 yoa- threshold age for imbalance in
antioxidant: oxidant: biomolecule homeostasis?
 NF-κB activation and inflammatory cascade
propagation
 ↓nNOS activity
 Physical Activity (lack thereof):
 Quality and Quantity
 Both factor and consequence of Sarcopenia
 Bidierctional nature w/ “self-perpetuating”
vicious cycle
• Feedback and Feedforward Loops

16. “Players” in Sarcopenia
 Atherosclerosis/ PVDz:
 Role of microcirculation/
endothelial health in regulating
nutrient delivery, anabolic and
catabolic stimuli
 Role of Apoptosis (individuality)
 Cumulative ultra-structural,
biochemical damage to
SReticulum and mitochondria 
Caspase enzyme cascade
 Variable depending on co-
morbidities/ genotype

17. Players in Sarcopenia
“Chicken or the Egg”
Sarcopenia ↓ Physical Activity
-Insulin Resistance
-Neuromuscular Maladapt.
-Cytokine Activity
-↓ Type IIa muscle fiber
-↓ Anabolic Hormone
-↓ Response to Exercise/
Nutritional Stimuli
- Oxidative Stress
- Anorexia
BIDIRECTIONAL

18. Sarcopenia of Aging VS. Cachexia
 Cachexia is a more aggressive,
involuntary general weight loss
(lean body AND fat mass)
occurring SECONDARY to a
chronic disease.
 Cancer, COPD, HIV/AIDS, CHF,
Rheumatoid Arthritis most
common for cachexia/wasting

20. Nutritional Strategies
Big Picture Basics:
 Maximize whole food nutritional platform
 Protein is “King” in the sarcopenic
population
 Current RDI is 0.8g/Kg/day
 Some data on benefit of 1.6g-2.0g/Kg/day
 Omega-3 lipids are “Princes” (higher
length DHA/EPA)
 Immuno-modulation, systemic inflammation,
proteasome inhib, eicosanoid milieu, insulin
sensitivity, mood/sleep quality, etc. [Calder
PC, 2002; Fearon et al. 2003; Smith et al. 2004]

21. Nutritional Strategies
 “CHRONO-Nutrition”
 TIMING, TIMING, TIMING! (yes, it works for
“grandma” and “grandpa” too)
 Nutritional Periodization for Seniors
 “Rational Polysupplementation”
 BCAAs (esp. Leucine):
 “Anti-anorectic” action via hypothalamic
serotonergic modulation
• Anorexia assoc w/ deranged Trp/5-HT metabolism;
Trp/LNAA ratio predict brain 5-HT concentrations
[Rossi et al. 1986; Cangiano et al. 1996]
 Promoting Protein Synthesis
 Inhibiting Proteolytic Pathways
[Ventrucci et al. 2004; Paddon-Jones et al. 2004; Poon et al.]

22. Nutritional Strategies
 HMB (and Arg, Lys, Gln) [May et al. 2002; Flakoll
et al. 2004]
 Protein vs. EAA vs. Prot-NRG
 Kinetics (that TIMING thing again)
 Feeding Pattern
 Leucine “fortification”
 Specific EAA profile (over-weighting in
certain “high impact” drug-like aminos)
 Creatine [Brose et al. 2003]
 MVI/ MMI
 Strategic Kcal/NRG Restriction vs. a
“Metabolic Mimetic”?

23. Nutritional Strategies
Honorable Mention
 Anti-Ox supplementation
 Potential to improve exercise tolerance,
insulin sensitivity, modulate
inflammation
 KIC
 Beta-Alanine
 Endocannabinoids
 Structured Lipids/ other PPAR-
alpha/delta agents
 L-Carnitine (PLCAR/ ALCAR)

24. Exercise Strategies
 Targeting FFR motor units
 Augment Type IIA (FOG)/ muscle fiber
CSA
 Role for occasional “Concentric emphasis”
sessions for insulin action/sensitvity [Asp S et
al. 1996; Kirwan JP et al. 1992]
 Resistance Training
 The MOST effective long-term intervention
for attenuating or preventing sarcopenia
[Frontera WR et al. 1988; Charette SL et al. 1991; Lexell
J et al. 1995; Vincent KR et al. 2002]
 Cadence (3-6s eccentric, 1-2s concentric 
progress to more explosive concentric)
 High yield compound, multi-joint exercises
 Important to account for individual’s training
history, limitations, med/surg history

25. Exercise Strategies
 Resistance Training (cont.)
 Training parameters for exercise
prescription  proper dose
response
 Volume, Load/ Intensity (70%-95%
1-RM), Frequency, Duration to
(Sarcoplasmic vs. Myofibrillar
hypertrophy)
 Periodize the loading parameters
and progressions to stay ahead of
the “adaptational curve” (2-5 week
intervals)
 Modify exercise selection,
parameters, program design to
“tailor” the exercise Rx long-term
• Purposeful, Goal-directed

26. Exercise Strategies
 Resistance Training (cont.)
 Strength training using 70-95% of 1RM
loads and Eccentric emph 
 Ultrastructural damage to contractile
proteins/ myofibrillar proteolysis [Evans WJ
et al. 1991; Frontera WR et al. 1988]
 Autocrine/Paracrine IFG, FGF, and PDGF
 ↑ prot synth and satellite cell activation
[Yamada S et al. 1989; Yan Z et al. 1993]
 Decreased Acute Phase Response to
RT in elderly (↓CK release, ↓PMN
mobilization, IL-1β) and PGs/eicosanoid
response  ↓ Adaptation and
Remodeling [Goldberg AL et al. 1988; Cannon JG
et al. 1994]

27. Exercise Strategies
 Cardiovascular Conditioning/ “Energy
Systems Training”
 More critical in the Sarcopenic-Obese population
 More “permissive” to improve recovery ability
and metabolic alterations from HI-RT (i.e. insulin
sensitivity, glucose tolerance)
 Appropriate Modality for individual
 Establish “Base” for ↑ Work Capacity (CO)
 Cardiorespiratory testing (likely “higher risk” –
ACSM class B, or C)
 Wider range of peak HR (50-80%)
 Monitoring becomes even more useful
 “Steady-state” and “IR-HIIT” protocols after
established good base  scaled down
appropriately

28. Exercise Strategies
 Other Modalities/ Considerations
 FES and “Hybrid”/Dynamic-FES assisted
“violates” Henneman’s Size Principle [Mahoney
et al. 2005]
 Whole body vibration/ “Power plate” options
to provide different overload in CKC
exercises
 Role for VOT/ Acute Focal Ischemia
 “Multi-Compound Complexes”
 Develop strength and function in multiple
planes
 Biomechanical/ Functional Anatomy
considerations to reduce injury risk and
improve training adaptations

29. Adjunctive Medical Treatment
 Anabolic Hormone therapy
 AAS (oxandrolone, nandrolone, testosterone esters)
 SARMs (Selective Androgen Receptor Modulators;
up and coming!)
 Peptides (hGH, hGH secretagogues)
• Dose/Duration Response
 SSRI/SNRIs
 “3 birds with one stone”  Mood, Sleep, and
Appetite
 Examples: Mirtazepine, Trazodone
 Megestrol Acetate
 Edema and disrupting the HPA axis (A bad thing!)
 Insulin Sensitizers (Biguanide class Metformin Vs. TZD-
PPAR agonists)
 Limit (caution with) NSAID use  affects muscle
protein metabolism following eccentric/resistance
exercise [Trappe TA et al. 2002]

30. Adjunctive Medical Treatment
 GHRH and IFG-I/IGFBP-3 complex as
safer alternatives to GH [Khorram et al. 2000;
Vittone et al. 2001;Sullivan DH et al. 1998]
 Testosterone replacement generally
better tolerated, and more effective in
improvement of global functional
status outcomes, mood states, and
strength (Prostate CA concerns overstated)
 Methodologic problems in many
previous studies; should adjust for
circulating T [Ferrando AA et al. 2002]

32. General Principles in
Sarcopenia Management
(Mx)
 Nutrition and Exercise Remain the
CORNERSTONE of Tx and Px
 Resistance exercise confers an amplified
anabolic response (MPS) from
exogenous AA +/- Insulin
 Maximize skel muscle mass during
young adult into middle age, to provide
reserves as buffer to catabolic stressors
 Likely a “threshold” lower limit amount of
skeletal muscle, beyond which see multi-
organ system dysregulation

33. General Principles in
Sarcopenia Mx
 Tailored EAA w/ precise AA profile
(e.g. overweighted in Leu, Lys, Phe, Met,
etc.)
 “Medicine is a science of uncertainty
and an art of probablility”
-William Osler
 Advances in Medicine, Nutrition, and
Exercise Science will elucidate previous
“uncertainties”…only to open another
“abyss of uncertainty”

34. Salient Points
 Sarcopenia
 major cause of disability and functional
decline
 imposes a modifiable economic burden w/
Health Care costs
 Multifactorial in origin, thereby requires
a multidisciplinary approach
 To optimize risk/benefit  regimen focused
on nutrition and exercise w/ potential for
structured, supervised anabolic Rx
 Focus on High-Intensity/Load PRT
(relative) to stop or reverse Sarcopenia

35. Salient Points
 Modify Protein and Carb intake to fit the exercise
needs/ goals of a particular day
 Consider on CV/NRG-sys days: Increased total
protein & carb (Pro:1.2g -1.6g/Kg bodyweight);
EAA “peri-workout”; ↑CHO/ BCAA/ Leu/ intake
throughout
 capitalize on increased gluc tolerance/insulin
senstivity; limit AA oxidation/catabolism
 Consider on Prog-Resistance Training days: (Pro:
1.0g – 1.6g/ Kg/day) with preference to “pulse”
midday; ↓CHO/↑Pro/healthy MUFA/PUFAs; high
‘anabolic efficiency’ EAA supplement “flanking”
peri-wkt and throughout the recovery period;
Leucine “fortification”
 facilitate skeletal muscle remodeling; support protein
anabolism

36. Salient PointsSalient Points
 Whey over Casein (in supplement); EAA
over Balanced AA; Animal over Vegetable
 “CHRONO-Nutrition”: ‘Pulse’ feeding pattern
w/ 65%-70% daily intake midday (e.g. flanking
the exercise session), 10%-15% of highly
efficient EAA/protein in am and pm
 “Rational Poly-supplementation”:
 Leucine and BCAA ‘enriched’ or ‘fortified’ protein
feeding/ EAA
 EPA/ DHA/ functional lipid supplementation
 Creatine w/ different dosing regimens (when and
if more data becomes available)
 ß-alanine + Creatine + Leucine/BCAA + EAA?
(more data needed)

37. Salient PointsSalient Points
 “Rational Poly-supplementation” (cont.):
 MVI/MultiMin and comprehensive, low-
dose, frequently dosed Antioxidant supp
 2nd
tier- β-ala, naturally occurring PPAR
modulators, Carnitines, etc. (as apporpriate
case by case scenario)
 Medical management (where
appropriate):
 Anabolic hormone Rx, Mood/Appetite
agents
 Molecular targets as they become
available
 Note: Many of these nutrition/suppl strategies
have yet to be studied using larger, RCTs in
healthy, elderly population

38. Anabolic vs. Catabolic Factors in Sarcopenia
-Testosterone
-IGF/ MGF/
PDGF/ NGF
-Insulin
Sensitivity
-Structured
Physical
Activity/RT
-Adequate
Protein/NRG
intake/
metabolic
response
-IL-6
-Ubiquitin-Proteasome/Caspases
-TNF-α
-tIL-1
-Cent/Periph Anorexic Sig
-Atherosclerosis (microcirc)
-Decreased α−Motor Neuron fxn
-Dec response to key Nutrients/
Hormones
CatabolicCatabolic
AnabolicAnabolic

39. Immune
System
Immune
System
Endocrine/
Metabolic
Endocrine/
Metabolic
Musculoskeletal
System
Musculoskeletal
System
Neural
support
Neural
support
•Vit D/ Ca++/PO4/Mg
•Protein
•EAA/ BCAA/ HMB/
KIC
•Creatine
•Functional Lipids
•Antioxidants
•Β-Alanine
•Chondro-protective
•7-keto-DHEA
•Creatine
•Acetyl-L-Car
•(other Aminos)
•Antioxidants
•Funct Lipids
•Phosphatidyl
Serine
•Protein
•Gln, Arg, BCAA
•Vit D
•Antioxidants
•Funct Lipids
•As Below
•ALCar/ PLCar
•Insulin Sensitizers
(R-ALA, + chiro-inositol,
Cinnamon extract, etc.)

40. Neural
Support
Immune
modulation
Muscle Protein
synthesis
Bioenergetic
Substrates
Muscle Protein
catabolism
Myogenic GF &
Satellite Cell
Activation
Systemic/ Local
Inflammation
Plasma
Membrane
Support
Multiple Pathways for
Augmenting the Training Effect
and Performance Adaptations
from a Complementary Approach

41. On the HorizonOn the Horizon
 Integrating molecular, pharmacologic,
exercise, and nutritional disciplines
 Biomolecular computing, nano-technology
applications
 Nutritional/ Exercise/ Pharmaco- Genomics
(Biomics tech)
• Truly establishing “tailored, precise
customization” in Exercise, Nutri/Supp, Molecular
targets/Pharma Rx
• “Physiatric” Genomics (Applied Exercise,
Nutrition, Meds, Rehab based on genomic data
for optimizing fxnl capacity, performance, and
QOL temp/perm disabled
 Seamless Fusion of Medicine, Performance
nutrition, Athletic performance, and Wellness
(My vision of “FitnessMD-
Integrated Medical Fitness model”)

42. On the HorizonOn the Horizon
 FAMuSS study (implications for sports
performance, health and sarcopenia)
 Exercise, Nutritional and Pharmaco-
Genomics/Proteomics
 Nascent stages
 Not yet changing Mx/Tx (recs benefit
the masses despite SNPs and SNP frequency)
 May alter ‘aggressiveness’ of Mx/Tx
(management/ treatment)
 Next Frontier brings “precise
customization” w/ molecular
targets, nutrition, and exercise

43. To learn more or ask a question,
click here to contact Dr. Lopez at
www.drhectorlopez.com
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