population: for the aging “enabling technologycrea.berkeley.edu/brooks-2004.ppt · role of...

“ENABLING TECHNOLOGYFOR THE AGING

POPULATION:From the lab to the Home”

Role of Physical Activity inManaging Obesity and Aging

George A. Brooks, Ph.D.George A. Brooks, Ph.D.Department of Integrative Biology , UC, BerkeleyDepartment of Integrative Biology , UC, Berkeley

““On the Go,From Head to Toe”

OutlineOutlineII I.I. Does Exercise Prevent Aging?Does Exercise Prevent Aging?II II.II. Why Exercise?Why Exercise?II III. III. How to Exercise?How to Exercise?

CardiovascularCardiovascularResistance and Resistance and PlyometricsPlyometrics

II IV.IV. Satellite Cells “Magic Bullets?”Satellite Cells “Magic Bullets?”

Does Exercise Prevent Aging?Does Exercise Prevent Aging?

II Yes?!Yes?!II No?!No?!II Exercise Slows Aging andExercise Slows Aging and

CompensatesCompensates for Aging Effects. for Aging Effects.

Why Exercise?Why Exercise?II Cardiovascular Fitness & HealthCardiovascular Fitness & HealthII Metabolic Fitness & HealthMetabolic Fitness & HealthII Muscular-Skeletal Strength, Flexibility &Muscular-Skeletal Strength, Flexibility &

HealthHealthII Freedom From InjuryFreedom From InjuryII Antioxidant DefensesAntioxidant DefensesII Sense of Well Being Sense of Well Being

Cardiovascular Fitness & HealthCardiovascular Fitness & Health

II Maximal Oxygen ConsumptionMaximal Oxygen Consumption(VO(VO22max) is the standard formax) is the standard forcardiovascular fitnesscardiovascular fitness

II VOVO22max is increased by regular,max is increased by regular,prolonged exerciseprolonged exercise

II VOVO22max declines with aging, but can bemax declines with aging, but can bemaintained at high levels despitemaintained at high levels despiteadvancing years.advancing years.

Measuring Maximal Oxygen Consumption (VO2max)

Figure 32-1 (b) y = V O2max (ml • kg -1 • min -1). Although training will improve V O2max and the quality of lifein the elderly, it will not prevent indefinitely the decline in functional capacity. x = age (hr). Adapted fromSuominen et al., 1980.

Cardiovascular Fitness & HealthCardiovascular Fitness & Health

II Regular prolonged exercise offersRegular prolonged exercise offersprotection against having cardiovascularprotection against having cardiovasculardisease (Decreases Morbidity)disease (Decreases Morbidity)

II Regular prolonged exercise offersRegular prolonged exercise offersprotection against dying fromprotection against dying fromcardiovascular disease (Decreasescardiovascular disease (DecreasesMortality)Mortality)

Figure 24-6 Deaths from CHD in longshoremen according to physical activity of work (range in kcal • min-1) and age at death. Shaded bars = heavy activity (5.2 - 7.5 kcal • min-1); unshaded bars = moderate and lightactivity (1.5 - 5.0 kcal • min-1). The relative risk of developing CHD for moderate and light exercise groupscompared to heavy exercise groups given above bars. Adapted from Paffenbarger and Hale, 1975.

Metabolic Fitness & HealthMetabolic Fitness & Health

II Regular Physical Exercise Helps toRegular Physical Exercise Helps toControl Age -Related Increases inControl Age -Related Increases inBody FatnessBody Fatness

II Regular Physical Exercise Reduces theRegular Physical Exercise Reduces theIncidence and Severity of Type IIIncidence and Severity of Type IIDiabetes (NIDDM).Diabetes (NIDDM).

Obesity* Trends Among U.S. AdultsObesity* Trends Among U.S. AdultsBRFSS, 1991, 1995 and 2000BRFSS, 1991, 1995 and 2000

(*BMI ≥ 30, or ~ 30 lbs. overweight for 5’4” person)1991 1995

2000

Source: Mokdad A H, et al. JAMA 1999;282:16, 2001;286:10.

No Data <10% 10%-14% 15-19% ≥20%

IN THEBEGINNING… And Now…

Chips

Councilmember Miriam Hawley (right) tests out the Segway Human Transporter in front of theCivic Center Tuesday with the help of Stacy Ferguson (left), Segway's director of public affairs."It's a wonderful thing (the Segway)," Hawley said. "I think it's a great mobility device."

Daily Cal(3/12/03)

Figure 25-2 Relationship of body mass index and the risk of death from all causes. SOURCE: Bray and Gray, 1988.

Crossover ConceptCrossover Concept

II Exercise prescriptions to oxidize body fatExercise prescriptions to oxidize body fatneed consider the Crossover Conceptneed consider the Crossover Concept

II At exercise intensities eliciting greater thanAt exercise intensities eliciting greater than45-50% VO45-50% VO22max, the body fuel selectionmax, the body fuel selectionswitches, crossover from, preponderance ofswitches, crossover from, preponderance oflipid to mainly carbohydrate (glycogen,lipid to mainly carbohydrate (glycogen,glucose, lactate).glucose, lactate).

0

25

50

75

100

5 25 50 75 100

% Fat% CHO

%VO2max

%

CH

O o

r Fa

t

Crossover Concept

Exercise Easier & Longer

Bear Valley Trail-Pt Reyes

Mild -Moderate Exercise

Bear Valley Trail to Arch Rock-Pt Reyes

Dr. Tom Budinger with his crew colleagues

Hard Exercise

From: NEJM 346(6), 2002

Exercise RecommendationExercise Recommendation

II If you like the lecture,If you like the lecture,

II Take a Hike.Take a Hike.


II If you don’t like the lectureIf you don’t like the lecture


II If you don’t like the lecture,If you don’t like the lecture,

II Take a Hike.Take a Hike.

Figure 17-1 Muscle tissue is composed of muscle bundles (fascicles), muscle fibers (cells), myofibrils, andmyofilaments (actin and myosin). From Edington and Edgerton, 1976, p. 16. Used with permission.

Figure 19-8 Relationship between number of motor units (MUs) and age in young and older men andwomen. There was a significant reduction in numbers of MUs with age ( P < 0.001). Adapted fromDoherty et al., 1993.

Figure 19-11 Weekly measurements of dynamic muscle strength (1-repetitionmaximum) of left knee extensors and flexors. Results are means ± SE. From Fronteraet al., 1988. Used with permission.

Figure 19-2 Serial sections ofquadriceps muscle from twodifferent athletes, stained withtwo different stains: (a) and(b) from an outstandingsprinter, (c) and (d) from anoutstanding distance runner.Sections (a) and (c) arestained for succinicdehydrogenase (SDHase); (b)and (d) stained for alkalinemyofibrillar-ATPase stain (M-ATPase). Note that fast fibers,which stain dark with M-ATPase, often are pale andstain weakly with SDHase. FT= fast-twitch fibers; ST = slow-twitch fibers. Note the twodark FT fibers in (d), which alsostain dark for SDHase in (c).These are FOG fibers (seeFigure 18-15). SOURCE:Gollnick, et al., 1972. Usedwith permission.

ST, Type IFT, Type II

Figure 19-13 Effects of strength training on the area of type I and type II fibers of vastus lateralis muscle ofthe left leg. Results are means ± SE. * Different from pretraining measurements ( P < 0.05). SOURCE:Frontera et al., 1988. Used with permission.

John Turner:Age 67John Turner:Age 67

Helen Zechmeister, Age 81Helen Zechmeister, Age 81Source: W. Evans

Professor Paola Timiras, 21+

What’s Happening?What’s Happening?

II Muscle Cell HypertrophyMuscle Cell HypertrophyII Muscle Cell HyperplasiaMuscle Cell Hyperplasia

Figure 17-3 An electron micrograph of a mature skeletal muscle from a ten-year-old boy. Asatellite cell ( Sat) is visible between the muscle ( M) fiber’s plasma membrane (Pm) and thebasement membrane ( Bm). Fibroblasts ( Fib) are visible in the extracellular space. Bar = 7µµµµm.SOURCE: H. Ishikawa, 1966.

Detection of nuclei in the active phase of growth. Nuclei in the activephase of growth were identified on day 4 (A) and day 8 (B) in the exercisedleg only using a Ki-67 antibody. Areas positive for Ki-67 stained brownwhile the nuclei were counterstained blue using haematoxylin.

Changes in satellite cells in human skeletal muscle after asingle bout of high intensity exercise Regina M. Crameri, HenningLangberg, Peter Magnusson, Charlotte H. Jensen, Henrik Daa Schrøder, Jens L. Olesen,Charlotte Suetta, Børge Teisne3 and Michael Kjaer J Physiol 558: 330-343, 2004.

Does Exercise Result in SatelliteDoes Exercise Result in SatelliteCell Activation and Muscle CellCell Activation and Muscle Cell

Hyperplasia?Hyperplasia?

Can Satellite Cell Activation beCan Satellite Cell Activation beused to Manage Sarcopenia inused to Manage Sarcopenia in

Aging?Aging?

How to ExerciseHow to ExerciseNew Technology-PlyometricsNew Technology-Plyometrics

Dr. Stan Lindstedt, NAU

Pronghorn Antelope

Muscles as springs: Absorbed energy isMuscles as springs: Absorbed energy isstored and recovered e.g., during runningstored and recovered e.g., during running

II Elastic recoil potential energyElastic recoil potential energyis used in running locomotionis used in running locomotionto enhance force productionto enhance force productionin the subsequent stride.in the subsequent stride.

II This property of muscle isThis property of muscle isboth time-dependent andboth time-dependent andadaptable.adaptable.

II Despite their prevalence inDespite their prevalence inmovement, lengtheningmovement, lengthening(eccentric) contractions are(eccentric) contractions arepoorly understood.poorly understood.Lindstedt et al., NIPS, 2001

If the force applied to a muscleIf the force applied to a muscleexceeds the force generated by it,exceeds the force generated by it,muscle absorbsmuscle absorbsmechanical workmechanical work

The absorbed work can The absorbed work canbe dissipated as heatbe dissipated as heat(muscle acts like a(muscle acts like ashock) e.g., when hikingshock) e.g., when hikingdownhill.downhill.

Lindstedt et al., J. exp. Biol., 2002

Lengthening contractions -Lengthening contractions - clinical applications clinical applications

Unique PropertiesUnique PropertiesMaximum force production is Maximum force production is MUCH MUCH (2-3x) greater(2-3x) greater(stimulus for muscle hypertrophy)(stimulus for muscle hypertrophy)Energy cost to produce force is Energy cost to produce force is MUCHMUCH (1/5) lower (1/5) lower

Unique ApplicationUnique ApplicationChronic eccentric training may be ideal forChronic eccentric training may be ideal forimproving locomotor muscle size, strength andimproving locomotor muscle size, strength andperformance in individuals for whom exercise isperformance in individuals for whom exercise islimited by oxygen uptake or delivery (e.g., CHF,limited by oxygen uptake or delivery (e.g., CHF,COPD).COPD).

Eccentric ErgometerEccentric Ergometer

3 hp motor drives3 hp motor drivespedals in reversepedals in reversedirection, thedirection, thesubject resists thissubject resists thismovement whilemovement whileattempting to matchattempting to matchtarget on screentarget on screenLaStayo et al., Am. J. Physiol., 2000

Adverse Responses ?Adverse Responses ?II NoNo significant leg pain significant leg painII NoNo significant rise in serum significant rise in serum

creatinecreatine kinasekinaseII NoNo significant drop in significant drop in

isometric force productionisometric force production

Leg StrengthLeg StrengthII Isomeric leg strengthIsomeric leg strength

was measuredwas measuredweekly.weekly.

II To account forTo account forlearning, we usedlearning, we usedweek three values asweek three values as“baseline”“baseline”

II Concentric controlsConcentric controlsimproved by 18%improved by 18%

II Plyometric subjectsPlyometric subjectsimproved by 60%improved by 60%

Isometric Strength (N)150 200 250 300 350 400 450

Timed U

p

10

12

14

16

18

20

High Fall Risk

Strength and Fall-Risk

Regular Concentric Training

Isometric Strength (N)150 200 250 300 350 400 450

Timed U

p

10

12

14

16

18

20

High Fall Risk

Low Fall Risk

Strength and Fall-RiskStrength and Fall-Risk

Plyometric Training

Weeks of Training1 2 3 4 5 6 7 8 9 10 11

68

101214161820

Very Light

Fairly Light

Hard

Somewhat Hard

Very Very Light

Very Hard

Very Very Hard

Exercise Intensity (RPE)Exercise Intensity (RPE)

Weeks of Training1 2 3 4 5 6 7 8 9 10 11

68

101214161820

Very Light

Fairly Light

Hard

Somewhat Hard

Very Very Light

Very Hard

Very Very Hard

Exercise Intensity (RPE)

-0

-300

-150

Total Negative Torque (N

m)

-250

-200

-100

-50

Will plyometricWill plyometric(eccentric) exercises(eccentric) exercisesprove more effectiveprove more effectivethat typicalthat typicalconcentric exercisesconcentric exercisesin promoting musclein promoting musclehyperplasia hyperplasia bybyactivating satelliteactivating satellitecells?cells?

Muscular-Skeletal Strength,Muscular-Skeletal Strength,Flexibility & HealthFlexibility & Health

II Muscle Strength Can Increase In theMuscle Strength Can Increase In theAgedAged

II Exercise Has a Role in Developing andExercise Has a Role in Developing andMaintaining the “Bone Bank”Maintaining the “Bone Bank”

II Increased Strength and CoordinationIncreased Strength and CoordinationCan Help Prevent Falls and ConsequentCan Help Prevent Falls and ConsequentInjuriesInjuries

Cervical Cancer

Annual Incidence of Common Diseases In Women

Osteoporotic Fractures > 1,000,000Heart Attack 513, 000Stroke 228,000Breast Cancer 182,000Uterine Cancer 32,000Ovarian Cancer 26,000

15,800

OSTEOPOROSIS

Source: CDC & W. Evans

OSTEOPOROSIS

Associated with 1.3 million fractures each yearAssociated with 1.3 Million Fractures Each Year

> 250,000 hip fractures

>240,000 wrist fractures

> 500,000 spinal fractures

Source: CDC & W. Evans

Stress and Bone DensityStress and Bone Density

II 3 - 4% increase in3 - 4% increase inbone density in 6bone density in 6monthsmonths

II 50 heel drops per50 heel drops perdayday

Bassey, E. J., Increase in femoral boneBassey, E. J., Increase in femoral bonedensity in young women followingdensity in young women followinghigh-impact exercise, Osteoporosishigh-impact exercise, OsteoporosisInternational 1994 4:72-75International 1994 4:72-75

Source: W. Evans

Control Exercise0

10

20

30BaselineFinal

Tim

eTi

me

(sec

onds

)(s

econ

ds)

Effects of strength training on balance:Effects of strength training on balance:

Backward Tandem Walk TimeBackward Tandem Walk Time

Source: W. Evans

Freedom From InjuryFreedom From Injury

II Freedom From Injury =Freedom From Injury =Freedom of MovementFreedom of Movement

Antioxidant DefensesAntioxidant Defenses

II Regular Physical Exercise Helps to IncreaseRegular Physical Exercise Helps to Increaseor Maintain Control Age -Related Decreasesor Maintain Control Age -Related Decreasesin Muscle Mitochondrial Mass andin Muscle Mitochondrial Mass andAntioxidant DefensesAntioxidant Defenses

II Training can result in Training can result in 100% Increments100% Increments in inMitochondrial Mass, Oxidative (RespiratoryMitochondrial Mass, Oxidative (RespiratoryEnzymes) and Related Enzymes for DefenseEnzymes) and Related Enzymes for DefenseAgainst Oxygen-Free RadicalsAgainst Oxygen-Free Radicals

Figure 6-3 Cross sections of humanskeletal muscle tissue illustratingthe sampling design used for analyz-ing muscle respiratory structures.The low-level magnification is usedfor assessing capillarity and fibersize. The intermediate magnificationallows for estimating the volume den-sity of mitochondria and other sarco-plasmic components. The highest mag-nification allows measurementof mitochondria compartmental spacesand membrane surface areas(arrows = capillaries; c= capillary;e = erythrocyte; mc = central mito-chondria; mf = myofibrils; cr = cristae; g = glycogen; gm = mi-tochondrial granule; ma = matrix; im= intermembrane space; om = outer mitochondrial membrane. SOURCE: Hoppeler, 1986. Used withpermission.

Figure 6-4 Cross section of a portion of a human muscle fiber exposing the A-and I-band andthe Z-line regions. Lipid droplets (li) are seen in contact with mitochondria (m). It is evidentthat the mitochondria in this muscle fiber form an extensively branched tubular network, orreticulum. SOURCE: Hoppeler, 1986. Used with permission.

MuscleMitochondrialmass and theMn-SODantioxidantenzyme doublewith training.

Metabolic Fitness & HealthMetabolic Fitness & Health

II Regular Physical Exercise Helps to ControlRegular Physical Exercise Helps to ControlAge -Related Decreases in Lean BodyAge -Related Decreases in Lean Body(Muscle) Mass(Muscle) Mass

II Regular Physical Exercise Helps to IncreaseRegular Physical Exercise Helps to Increaseor Maintain Control Age -Related Decreasesor Maintain Control Age -Related Decreasesin Muscle Mitochondrial Mass andin Muscle Mitochondrial Mass andAntioxidant DefensesAntioxidant Defenses


HealthHealthII Freedom From InjuryFreedom From InjuryII Antioxidant DefensesAntioxidant DefensesII Sense of Well BeingSense of Well Being

Sense of Well BeingSense of Well Being

II Physical Exercise Improves MoodPhysical Exercise Improves MoodII Physical Exercise May Promote IncreasesPhysical Exercise May Promote Increases

in Levels of Brain-Derived Neurotrophicin Levels of Brain-Derived NeurotrophicFactor (BDNF) and other Growth FactorsFactor (BDNF) and other Growth Factors(IGF & FGF).(IGF & FGF).

II BDNF Expression Appears to Increase InBDNF Expression Appears to Increase InActivity- and Cognition-Related AreasActivity- and Cognition-Related Areassuch as the Hippocampus.such as the Hippocampus.

From: Carl W. Cotman & Nicole C. Bechtold, UC, IrvineTrends In Neurosci. 25: 295-301, 2002.

From: Carl W. Cotman & Nicole C. Bechtold, Institute for Brain Agingand Dementia and Department of Neurology, UC, Irvine

Though I look old, yet I am strong and lusty;Though I look old, yet I am strong and lusty;For in my youth I never did applyFor in my youth I never did applyHot and rebellious liquors in my bloodHot and rebellious liquors in my bloodNor did not with unbashful forehead wooNor did not with unbashful forehead wooThe means of weakness and debility;The means of weakness and debility;Therefore my age is as a lusty winter,Therefore my age is as a lusty winter,Frosty, but kindly. Let me go with you;Frosty, but kindly. Let me go with you;I’ll do the service of a younger manI’ll do the service of a younger manIn all your business and necessities.In all your business and necessities.

William ShakespeareWilliam Shakespeare, As you like it, As you like it, Act II,, Act II,Scene III, lines 46-55Scene III, lines 46-55

Exercise RecommendationsExercise Recommendations

Take a Hike!Take a Hike!


Take a Hike!Take a Hike!Take a Bike!Take a Bike!


Take a Hike!Take a Hike!Take a Bike!Take a Bike!Take a Boat!Take a Boat!


Take a Hike!Take a Hike!Take a Bike!Take a Bike!Take a Boat!Take a Boat!

Take a Rocket!Take a Rocket!

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