Allostasis, Homeostasis, and Fluidomechanic Effect of Exercise

in Maintaining Health Condition

Damayanti Tinduh

Division of Sport Injury Rehabilitation, Department of Physical Medicine & Rehabilitation,

Dr. Soetomo General Hospital, Faculty of Medicine, Univeristy of Airlangga, Surabaya, Indonesia

daniellarosita@yahoo.com

Keywords: Health Related Physical Fitness, Homeostasis, Allostatic State, Exercise, Fluidomechanic

Abstract: Noncommunicable diseases (NCDs) are responsible for more than 68-75% of deaths. Leading risk factors

for premature death include physically inactivity, obesity, hypertension and smoking. Health related

physical fitness (Hr-Pf) is the way to prevent these comorbidities, consist of cardiorespiratory endurance,

body composition, muscular strength, muscular endurance and flexibility. The principle of maintaining Hr-

Pf are maintaining homeostasis state, stabilizing the body system during changes, strengthening body

system to bear the allostatic load and achieving the better homeostasis state. This article will discuss about

how the body response to the changes of homestasis, allostatic state and allostatic load during life and the

role of fluidomechanic adaptation during exercise affects the allostatic state in cellular to tissue level.

1 INTRODUCTION

Noncommunicable diseases (NCDs), such as

diabetes, cardiovascular diseases, cancer, chronic

respiratory diseases, and mental disorders are

responsible for more than 68% of deaths worldwide

and 75% of deaths in low- and middle-income

countries. Leading risk factors for premature death

include physical inactivity, obesity, hypertension,

and smoking. Physical fitness from exercise can

prevent the reduced cardiorespiratory fitness, which

represents a global public health problem, that in

turn leads to morbidity, disability and mortality of

some diseases. Health-related physical fitness (Hr-Pf)

components consists of cardiorespi-ratory endurance,

body composition, muscular strength, muscular

endurance and joint flexibility.

The principle of maintaining Hr-Pf are

maintaining homeostasis state, stabilizing the body

system during changes, strengthening body system

to bear the allostatic load and achieving the better

homeostasis state. Homeostasis is an ability of the

body to seek and maintain a condition of equilibrium

or stability within its internal environment when

dealing with external changes, a dynamic process

continuously. This process clamps each internal

parameter at a “set point” by sensing errors and

correcting them with negative feedback (Berntson

and Cacioppo, 2007).

2 DISCUSSION

2.1 Homeostasis: Adjustment to

Failure.

Homeostasis refers to the processes by which the

constancy of the fluid matrix is maintained. During

maintaining the equilibrium, there are conditions

ranged from adjustments (health state) to failures

(illness/injured state), which can occur progressively

(Figure 1). Homeostasis processes may continue to

operate at the basic regulatory level, being sensitive

to internal physiological stimuli that signal

deviations from a regulated set point. Exogenous

stimuli may reset regulatory levels, either directly or

via a humoral route, to facilitate resistance or

adaptation to the exogenous stressor. Such

readjustments of set-point deviate from homeostatic

or hemodynamic processes, as they represent active

alterations of the regulatory level, named

Heterostasis. Heterostatic regulation could be

affected by the changes of hormones and the

Tinduh, D.

Allostasis, Homeostasis, and Fluidomechanic Effect of Exercise in Maintaining Health Condition.

DOI: 10.5220/0009090203210330

In Proceedings of the 11th National Congress and the 18th Annual Scientiﬁc Meeting of Indonesian Physical Medicine and Rehabilitation Association (KONAS XI and PIT XVIII PERDOSRI

2019), pages 321-330

ISBN: 978-989-758-409-1

321

chemical environment of the body (Bertnson and

Cacioppo, 2007).

Figure 1: Adjustment to failure (Berntson and Cacioppo,

2007)

2.2 Allostasis : Stability Through

Change.

Regulatory levels are not fixed, but may be flexibly

adjusted to meet changing demands. The

uncompensated condition is occurred when the

stressors overcome ability of the body to compensate

the changes. This condition is called allostasis.

Allostasis is a wide range of functioning of the

coping/adaptation systems, depending on a variety

of factors. Many visceral dimensions are regulated

by multiple interacting mechanisms that are subject

to a wide range of modulatory influences, that

reflecting the natural adaptive readjustment of

regulatory levels in changing physiological demands.

It reflects the operations of higher neural systems

that control and integrate a broad range of more

basic “homeostatic” reflexes (Berntson and

Cacioppo, 2007).

Sympathetic-Adrenal-Medullary (SAM) axis

(which release catecholamines) and Hypothalamus-

Pitutary-Adrenal (HPA) axis (which produce

glucocorticoids) are regulatory systems involved in

allostasis (Bertson and Cacioppo, 2007).The goal of

this process is not constancy, but rather fitness under

natural selection, with strategies of preventing errors

and minimizing costs, using prior information to

predict demand and then adjusting all parameters to

meet it. This process is triggered by allostasis

load/stress, which has consequences of cost (coping

or adaptation), wear and tear on the brain and body,

and if the ongoing stress continues, the stress

responses never turn off and lead to illness and

disease.

2.3 Allostatic Load

Generalized model of stress response, shifted the

focus from the autonomic nervous system to the

pituitary adrenocortical system, termed the General

Adaptation Syndrome (GAS) (2). General adaptation

syndrome is the sum of all non-specific, systemic

reactions of the body which ensue upon long

continued exposure to stress, giving the predictable

pattern of physical response. It consists of alarm

reaction, resistance stage and stage of exhaustion.

Alarm reaction is an initial shock response from

autonomic nervous system activation within first 6-

48 hours after stress (reduced activity). After few

days (48 hours – 1 months after stress) of prolonged

stress, the organism entering the resistance stage

(adrenocorticosteroid response), seems to adapt to

the stress and return to normal. In the stage of

exhaustion, the acquired adaptation to the stress is

lost because of depletion of defensive resources

within 1-3 months after stress (Bertnson and

Cacioppo, 2007).

Allostatic load can be measured by parameters :

1) Systolic and diastolic blood pressure (indices of

cardiovascular activity); 2) Waist-hip ratio (an index

of more chronic levels of metabolism and adipose

tissue deposition, thought to be influenced by

increased glucocorticoid activity); 3) Serum HDL

and Total Cholesterol (related to the development of

atherosclerosis – increased risks being seen with

higher levels in the case of total cholesterol and

lower levels in the case of HDL; 4) Glycosylated

hemoglobin plasma (an integrated measure of

glucose metabolism over several day times); 5)

Dihydroepiandrosterone sulfate (DHEA-S) serum (a

functional HPA axis antagonist); 6) Overnight

urinary cortisol excretion (an integrated measure of

12-hr HPA axis activity); 7) Overnight urinary

noradrenalin and adrenalin excretion (integrated

indices of 12-hr sympathetic nervous systems

activity)

Allostasis causes the allostatic states within

tissues and cells, giving load (allostatic load) that

affect physical and mental health (Figure 2).

Allostatic states reflect tissue and cell’s response to

allostatic changes (Pederson, 2019 see Table 1

KONAS XI and PIT XVIII PERDOSRI 2019 - The 11th National Congress and The 18th Annual Scientiﬁc Meeting of Indonesian Physical

Medicine and Rehabilitation Association

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Figure 2: Allostasis, allostatic states and allostatic load (Juster et al, 2016)

Table 1: How the body function response to the stress

2.4 Mitochondrial Allostatic Load

(MAL)

Chronic stress perturbs adaptive glucocorticoid

signaling and glucose levels that in turn alter

mitochondrial structure and function, generating

oxidative stress and cellular damage. This process

cumulatively worsens risk factors, which

consequently leads to disease. In this multilevel

cascade, mitochondrial dysfunction is depicted as an

early event mediating the relationship between

primary mediators of chronic stress and disease

trajectories (Figure 3) (Juster, 2016).

Mitochondrial allostatic load (MAL) leads to

mitochondrial dysfunction, with the manifestations

of decreased energy production, increased oxidative

stress, pro-apoptotic signaling, mitochondrial DNA

copy number alteration, mitochondrial fragmentation,

pro-inflammation signaling and transcriptional

changes. Physical activity and healthy diet inhibit

the allostatic load become MAL, but poor sleep and

physical inactivity leads MAL trigger the

Allostasis, Homeostasis, and Fluidomechanic Effect of Exercise in Maintaining Health Condition

323

dysfunction of specific tissue/organ, that in turn

leads to comorbidity that can be seen as clinical

phenotype (Juster, 2016).

Figure 3: The stress-disease cascade and mitochondrial alloastatic load (Juster, 2016)

2.5 Physiological Toughness Model

Shorter duration of the stress response could reduce

the allostatic load and overall wear and tear on the

body. Evidence suggests that fitness or exercise

training may provide a more rapid recovery from the

stressor once it is no longer present. Exercise can

reduce the immediate effects of stress and enhance

the recovery process from stressors. Intermittent but

regular exposure to stressors (e.g., regular exercise)

lead to psychological coping, emotional stability,

and physiological changes, giving adaptive

performance in challenge/threat situations,

enhancement of immune system function, and

greater stress tolerance. Physical activity and

exercise give the benefits such as lowering the risk

of death from any cause and in improving longevity,

comparable to drug intervention (Pedersen, 2019).

2.6 Exercise and Blood Flow

Popliteal artery was impaired after 5 days of reduced

daily physical activity (from >10,000 steps/day to

<5,000 steps/day), because decrease in blood flow

and thus shear stress, which is an important stimulus

for maintaining endothelial health. This impairment

can be abrogated by increasing leg vascular shear

stress with leg muscle contraction (Teixeira et al,

2017). Muscle contraction during exercise increases

the muscular blood flow from muscle pump effect,

vasodilator mechanisms and blunting of sympathetic

vasoconstriction in contracting muscles (Joyner and

Casey, 2015). Muscle blood flow is closely matched

to the metabolic demands of contraction, which

occurs across a range of intensities from rest to

heavy exercise and during both small and large

muscle mass exercise, in response to both single

contractions and more prolonged exercise lasting for

hours (Joyner and Casey, 2017). In human subject,

exercise training for 4 weeks increase blood flow

capacity (BFC) as measured by reactive hyperemic

responses to occlusion of blood flow on limbs. The

increase of BFC depends on mode of training and

interaction of muscle fiber-type composition with

muscle fiber recruitment pattern during exercise.

Sprint training has been shown to increase

contractile activity in fast-twitch, white skeletal

muscle. In contrast, endurance training has been

shown increase in contractile activity slow-twitch,

red skeletal muscle. Both modes increase oxidative

capacity, capillary density and BFC, but sprint mode

also triggers changes in vascular cells (Laughilin and

Roseguini, 2008).

Increased oxygen demand in exercise is reflected

as VO2max, an important factor that increases the

blood flow. The variability of VO2max is affected

by body composition, level of physical activity,

blood volume, hemoglobin mass, stroke volume and

“genetic” factors (Joyner and Casey, 2015).

Treadmill exercise is one of exercise mimicking

natural walking activity, recruits the small and large

muscle mass to contract. As the type of exercise,

Treadmill exercise should have the specific dose,

which the goal is improving the overall fitness

which is reflected by VO2max. Uda’a et al reported

that in untrained healthy young males, VO2max

increased 17% (p=0.000) after 4 weeks of moderate-

intensity Treadmill exercises with the modes of

KONAS XI and PIT XVIII PERDOSRI 2019 - The 11th National Congress and The 18th Annual Scientiﬁc Meeting of Indonesian Physical

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graded increase in speed and graded increase in

inclination, and no significant differences between

these two modes (Uda’a et al, 2019), but they

showed the different heart rate response due to the

different modes (graded increase in inclination vs

speed) of moderate intensity Treadmill exercise

(Figure 4) (Hendrarati,et.al,2019).

A B

Figure 4: Heart rate response of untrained healthy young males exercise with moderate intensity (70% maximal heart rate)

graded increased inclination Treadmill exercise (A) and graded increase speed Treadmill exercise (B) for 30 minutes

(Hendrarati et al, 2019).

The peak of target heart rate is achieved earlier

in the mode of graded increase in speed (start on

minute 3) than graded increase in inclination (start

on minute 11) (p=0.006). The duration in

maintaining the target heart rate longer in increased

speed mode (19 minutes) compared to increased

inclination mode (11 minutes) (p=0.000) (Hendrarati

et al, 2019). Longer duration to maintain the muscle

exercise, more oxygen and metabolism demand

occur, more increase in mitochondrial activity and

cellular expression.

Increased blood flow will increase shear force on

tissue to cell (Figure 5). Force is transferred across

multiple length scales (left) while tissues adapt to

the dynamic mechanical environment (right).

Together, the transfer of force from the environment,

and subsequent structure-function adaptation of the

system constitute the dynamic process of functional

adaptation, also referred to as mechanoadaptation

(Ng JL et al, 2017).

Figure 5: Adaptation to force in tissue to cell (Ng JL et al, 2017).

Time (minutes)

Heart Rate (bpm)

Allostasis, Homeostasis, and Fluidomechanic Effect of Exercise in Maintaining Health Condition

325

Blood cellular mechanoadaptation affect the

hemorheology. Human blood is a non-Newtonian

fluid, so viscosity is not constant at different flow

rates. Whole blood viscosity (WBV) is dependent on

the shear rate and changes in a non-linear

relationship (WBV decreases with higher shear rate)

and the temperature (WBV decreases with high

temperatures). The principal determinants of WBV

are hematocrit, red blood cell (RBC) deformability

and plasma viscosity (Cowan et al, 2012).

Hematocrit and plasma viscosity rose with exercise,

while erythrocyte elongation index is lowered. Acute

response of submaximal aerobic exercise (70%

HRmax) for 1 hour does not change the blood

viscosity, erythrocyte aggregation and ﬁbrinogen, in

both young people and adults (Romagnolia et al,

2014). But regular (chronic) exercise decrease

hematrocrit (I

=96.46%), red blood cell aggregation

=94.95%) & plasma viscosity (I

=99.25%)

(Figure 6)(Romain et al, 2011).

Figure 7. Physical activity and endothelial function (1Kim

B et al, 2014)

Figure 6: Shear rate and Whole Blood Viscosity.

Shear force/stress is needed for functioning

vascular endothelial. Increased in intensity and

duration of shear stress from increased blood flow,

will increase endothelial Nitric Oxide Species

(eNOS) expression and in turn affect the longevity

(anti-apoptotic, anti-inflammatory) and function of

endothel (vasodilatation, anticoagulation,

antiadhesion, fibrinolysis). This mechanism is

showed in Figure 7 (Thosar et al, 2012).

2.7 Exercise and Cellular Mechanical

Forces.

Mechanical forces (MF) working in cell consist of

external and internal MF. External MF is defined as

forces, such as tensile, compressive or shear stresses

that are applied to cells from their environment,

specifically. Internal MF referred to intercellular

tension, which can be done by cross bridging of

actomyosin, focal adhesion (cell traction

forces/CTFs) and substrate stiffness (Wang and Li,

2010).

Figure 8: Schematic illustration of the mechanical nature

of cellular mechanotransduction mechanism (Wang and Li,

2010).

MF can induce mechanotransduction by directly

altering conformation of an extracellular matrix

(ECM) protein and integrin configuration and

KONAS XI and PIT XVIII PERDOSRI 2019 - The 11th National Congress and The 18th Annual Scientiﬁc Meeting of Indonesian Physical

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326

transmitting forces to the cytoskeleton and nucleus,

then eventually affecting transcription and

translation. MF can unfold a domain of the

extracellular protein (M) and expose a cryptic site

that may serve an activating ligand for a cell surface

receptor, resulting in a series of signaling events.

When MF is applied to force receptor (FR), such as

integrin and G protein, they initiate signal

transduction, lead to transcription followed by

translation. As a result, soluble factors are secreted

into the ECM, which act on the receptor (R) and

then initiate a cascade of signaling events (Wang

and Li, 2010).

In vivo cells integrate and interact with a

microenvironment comprised of a milieu of

biochemical, biomechanical, and bioelectrical

signals derived from surrounding cells, ECM and

soluble factors. These components vary in both time

and space and are integral to the regulation of

cellular behaviors. The biological, chemical, and

mechanical properties of biomaterials can also be

tuned to further control the cellular

microenvironment (Selimovi et al, 2013).

2.8 Exercise and Extracellular Matrix

In contracting skeletal muscle, lower levels of

extracellular matrix (ECM) crosslinking reduce the

stiffness of skeletal muscle, resulting in improved

mechanical properties and mechanotransduction to

the resident stem cells. Resistance training (RT)

reduces fat inﬁltration in aging skeletal muscle and

is an effective strategy to maintain skeletal muscle

mass and cross-sectional area with age. RT blunted

the age-induced accumulation of connective tissue

concomitant to the up regulation of genes related to

the synthesis (COL-1A1/COL-3A1; TGFβ and

CTGF) and degradation (MMP-2/MMP-9; TIMP-

1/TIMP-2) of the ECM network. Exercise training

can potently stimulate stem cell activation and

positively inﬂuence skeletal muscle ECM

remodeling in a manner that suggests both factors

are important and perhaps codependent in their

ability to improve and/or maintain muscle structure

and function following a physiological stimulus

(Uda’a et al, 2019).

Figure 9: Schematic representation of the skeletal muscle stem cell niche (A) and its alteration postexercise (B). Exercise

results in increased mesenchymal stem cell (MSC) accumulation and ECM reorganization facilitated by matrix

metalloproteinases (MMPs) (Modified with permission from Taylor & Francis Ltd. (http://www.tandfonline.com) (Garg

and Boppart, 2016)

2.9 Exercise and Endocrine Effects

Activated muscle contraction during exercise, act as

endocrine organ and communicate with other organs.

Brain-derived neurotropic factor (BDNF) and

Interleukin (IL)-6 are involved in 5’-AMP-activated

protein kinase (AMPK)-mediated fat oxidation. IL-6

stimulates lipolysis, involved in glucose and lipid

metabolism and stimulates cortisol production (only

during exercise), neutrocytosis and lymphopenia.

Irisin is involved in the “browning” of white adipose

tissue (Pedersen, 2019). In untrained young healthy

males, Irisin serum significantly increase acutely

after 1 session of moderate intensity Treadmill

exercise with graded increase in speed mode

(p=0.002), but not in graded increase in inclination

mode. The baseline Irisin serum increased 5% after

2 weeks exercise (Uda’a et al, 2019). In the same

subjects, baseline BDNF serum increased

significantly (111%) after 2 weeks of moderate

intensity Treadmill exercise with graded increase in

Allostasis, Homeostasis, and Fluidomechanic Effect of Exercise in Maintaining Health Condition

327

speed mode (p=0.001), but not in graded increase in

inclination mode. There was no significant acute

response in BDNF after exercise (Yulinta et al,

2019). This facts showed that each myokine have

specific response in term of mode of exercise and its

role on the specific target organ.

The muscle secretome consists of several

hundred secreted peptides, as communicator with

other organ. IL-4, IL-6, IL-7, IL-15 and LIF

(Leukemia Inhibitory Factor) promote muscle

hypertrophy. Myostatin inhibits muscle hypertrophy

and exercise leads to liver secretion of the myostatin

inhibitor follistatin. IL-6 also increases insulin

secretion by inducing the expression of Glucagon

Like Peptide (GLP)-1 by the L cells of the intestine.

IL-6 has anti-inflammatory effects because it

inhibits TNF production and stimulates the

production of IL-1ra and IL-10. Duration, intensity

of exercise, muscle mass engaged during exercise,

the muscular glycogen level and whether or not

carbohydrate is ingested during the exercise

determine the magnitude of the systemic IL-6

response. IL-6 inhibits lipopolysaccharide-induced

TNF-alpha production in monocytes (Pedersen,

2019). Baseline of IL-6 serum reduced significantly

after 2 weeks of moderate intensity Treadmill

exercise in untrained young healthy males, reflected

the potency of exercise to reduce the baseline

inflammatory status in these subjects (Wulan et al,

2019).

Figure 10: Skeletal muscle is an endocrine organ (Pedersen, 2019)

2.10 Adaptation Process of Physical

Exercise

Exercise can reduce the immediate effects of stress

and enhance the recovery process from allostatic

load, as a role of fluidomechanic during muscle

contraction as stated above (Teixeira et al, 2017. The

dose response of exercise is very important thing

and should be adjusted to achieve optimal exercise

response, to meet the allostatic state demand.

Depend on the exercise intensity, the body reactions

can be classified as in the table 2 below. High

activation state is the safe and efficient state to get

benefit of the exercise for maintaining the fitness

and health status, and we should pay attention

carefully if the exercise is in overactivation state. It

should be done in brief and be controlled to increase

the toughness of body systems. The longer period of

overactivation state would lead to more allostatic

load, and reduce the survival capability of cells.

KONAS XI and PIT XVIII PERDOSRI 2019 - The 11th National Congress and The 18th Annual Scientiﬁc Meeting of Indonesian Physical

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Table 2: Body Response to Exercise.

3 CONCLUSION

Human body underwent the changes in every time

and situations, which can help the body system to

surpass the stress condition. For maintaining normal

body function, toughness of physiological response

is very important factors. Exercise is a nice

orchestration of muscle contraction and

fluidomechanic to activate the cellular to organ

system for giving the best response to every change

and prevent the body from adaptation failure (injury

or disease).

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Medicine and Rehabilitation Association

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