












































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































































ANNALES KINESIOLOGIAE • 8 • 2017 • 1

23

Review article       UDC: 796.011:616-053.9
received: 2017-07-03

EXERCISE AND THE AGEING IMMUNE SYSTEM

Ana PETELIN1, Nina MOHORKO1

1University of Primorska, Faculty of Health Sciences, Polje 42, SI-6310 Izola, Slovenia

Corresponding author: 
Nina MOHORKO 

University of Primorska, Faculty of Health Sciences, 
Polje 42, 6310 Izola, Slovenia. 

Tel.: +386 5 66 35 802
e-mail: nina.mohorko@fvz.upr.si

ABSTRACT

Life expectancy in the developed world has increased exponentially over the last 
century. There is now a strong body of evidence demonstrating that aging is accom-
panied by severe alterations in the immune system, a process known as “immunosene-
scence”, commonly defined as the functional decline of the adaptive immune system 
with age. Inflamm-aging, a chronic progressive increase in the inflammatory status 
has attracted great attention in recent years in age-related research field. This process 
plays an important role in the age-related diseases, such as heart disease, atheroscle-
rosis, Alzheimer’s disease, type II diabetes, among others. Exercise impacts immune 
function both acutely and chronically. This article describes how exercise activates the 
release of hormones, myokines and cytokines, as well as modulates the expression of 
various immune-reactive molecules, which all contribute to anti-inflammatory effects 
and possible attenuation of immunosenescence.

Keywords: immunosenescence, inflamm-aging, exercise 

GIBANJE IN IMUNSKI SISTEM MED PROCESOM STARANJA 

IZVLEČEK

V zadnjem stoletju je pričakovana življenjska doba v zahodnem svetu eksponentno 
narasla. Staranje spremljajo velike spremembe v imunskem sistemu. Ta proces, ime-



24

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

ANNALES KINESIOLOGIAE • 8 • 2017 • 1

novan imunosenescenca, je definiran kot funkcionalni upad adaptivnega imunskega 
sistema s staranjem. Za staranje je značilno tudi progresivno naraščanje vnetja, ki ima 
pomembno vlogo pri s staranjem povezanih boleznih, kot so bolezni srca, aterosklero-
za, Alzheimerjeva bolezen, sladkorna bolezen tipa 2 in druge. Gibanje vpliva na imun-
ski sistem tako akutno kot kronično. Gibanje povzroči sproščanje hormonov, miokinov 
in citokinov in spremeni ekspresijo različnih z imunostjo povezanih molekul, kar vpliva 
na protivnetne učinke in zmanjšanje imunosenescence, kar opisuje članek.

Ključne besede: imunosenescenca, s staranjem povezano kronično vnetje, gibanje

INTRODUCTION

Life expectancy in the developed world has increased exponentially over the last 
century. There is now a strong body of evidence demonstrating that aging is accompa-
nied by severe alterations in the immune system, a process known as “immunosene-
scence”, commonly defined as the functional decline of the adaptive immune system 
with age. Indeed, according to Arnold et al. (2011), the assurance of longevity and 
healthy aging occurs by maintaining the integrity of immunity. The worldwide increase 
of the proportion of people older than 65 years has led to the rising costs of age-related 
diseases; therefore, a better understanding of immunosenescence could help us to limit 
the development and progression of age-related diseases.

Immunosenescence results from the accumulation of molecular and cellular defects 
due to thymic involution (the age-related reduction in thymus size and activity), oxi-
dative damage, and hyper stimulation of both the innate and adaptive immune system. 
Thymic involution results in significant exhaustion of naive T cells, and the shrinkage 
of the T-cell repertoire (Nguyen, Mendelsohn, & Larrick, 2017). Moreover, the progres-
sive functional B lymphocyte deficits have also been suggested as the main responsible 
factors for age-associated disorders (Gruver, Hudson, & Sempowski 2007). However, 
in general, all immune cells are affected by aging, but the adaptive response seems to be 
more affected by the age-related changes in the immune system (Franceschi, Bonafè, & 
Valensin, 2000). Poor immune function in elderly combined with continued exposure 
to antigens, results in chronic activation of macrophages and other pro-inflammatory 
cells and contributes to chronic low-level systemic inflammation common in older age 
(Franceschi et al., 2000). 

INFLAMMATION, OXIDATIVE STRESS AND AGING

Chronic low-grade systemic inflammation is a common manifestation of aging. 
While acute inflammation is normally tightly controlled and is a part of the common 
physiological healing processes, low-grade systemic inflammation describes a chronic, 



ANNALES KINESIOLOGIAE • 8 • 2017 • 1

25

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

mostly asymptomatic, low-grade inflammatory state that can eventually lead to chronic 
illness in the elderly such as cardiovascular diseases (CVD), diabetes, osteoarthritis, 
obesity, physical disability, Alzheimer’s disease (AD), sarcopenia, among others (Sin-
gh & Newman, 2011). But, as with all other physiological systems, with aging there are 
also significant declines in the immune function that promote inflammation (Chung et 
al., 2009). Age-related chronic inflammation is often attributed to the immune system 
(Franceschi et al., 2000; Vasto et al., 2007), because as we age, we accumulate an “an-
tigenic burden,” the sum of all the antigenic stresses (both internal and external) that 
we unavoidably encounter throughout life, which causes the progressive activation of 
macrophages and other immune-cell types. This low-level chronic activation leads to 
the continuous production of inflammatory factors such as cytokines and chemokines, 
which raises the basal levels of these factors throughout the body. This process, termed 
“inflamm-aging” has been thoroughly described elsewhere and is supported by a sub-
stantial body of data (Franceschi et al., 2000; Singh & Newman, 2011). Indeed, 2-4 fold 
increase in the primarily serum levels of pro-inflammatory cytokines such as interleu-
kine-7 (IL-7), IL-6, tumor necrosis factor-α (TNF-α) and acute phase proteins such as 
C-reactive protein (CRP) are typical for aged individuals when compared to younger 
individuals, even in the absence of chronic diseases (Bruunsgaard, 2006; Vasto et al., 
2007; Xia et al., 2016). Thus, circulating levels of inflammatory mediators such as IL-6 
and CRP have been found to be useful prognostic markers in very old people (Jylhä et 
al., 2007; Singh & Newman, 2011). Indeed, elevated levels of IL-6 and TNF-α in the 
serum of elderly have been found to be associated with some diseases (De Martinis, 
Franceschi, Monti, & Ginaldi, 2005). IL-6 is a pro- and anti-inflammatory cytokine 
produced by the cells of the immune system, vascular endothelial cells, adipocytes, and 
skeletal muscles. Another cytokine, TNF-α is produced mainly by macrophages, but 
also by vascular endothelial cells, adipocytes, and some others, and has been shown to 
increase muscle protein degradation and impair muscle protein synthesis. Its elevated 
levels have been observed in many inflammatory diseases, such as osteoarthritis, rhe-
umatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, 
metabolic syndrome, type 2 diabetes mellitus and congestive heart failure (Thomas, 
2013). CRP is an acute phase protein produced by the liver and its levels are up-regu-
lated in response to elevation in IL-6 (Singh & Newman, 2011). The exact mechanism 
for the increase in pro-inflammatory cytokines with age is still not fully understood.

Accumulating evidence indicates that obesity and systemic inflammation are highly 
interrelated. Obesity is associated with diabetes and CVD as well as growing num-
ber of other diseases with inflammatory components including dementia and cancer 
(Knight, 2011). Adipose tissue (AT) acts as an endocrine organ by releasing some pro- 
and anti-inflammatory cytokines, which originate from adipose cells and/or infiltrated 
macrophages (Ouchi, Parker, Lugus, & Walsh, 2011). AT is infiltrated with macropha-
ges in two separate polarization states: M1, which produce pro-inflammatory cytokines 
and M2, producing anti-inflammatory cytokines. Therefore, it has been proposed that 
in AT a phenotypic switch takes place toward macrophages of the M1-phenotype, pro-
moting the inflammatory state (reviewed in Müller & Pawelec, 2014).



26

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

ANNALES KINESIOLOGIAE • 8 • 2017 • 1

Moreover, increases in oxidative stress with aging may also contribute to the deve-
lopment of chronic inflammation and disease (Cannizzo et al., 2011). There are several 
potential mechanisms linking oxidative stress to inflammation (Xia et al., 2016). Aging 
is associated with increases in both tissue and circulating levels of reactive oxygen 
species (ROS) as well as a decline in antioxidant capacity (Kregel & Zhang, 2007). To 
protect itself, organisms have developed various antioxidative defenses that include 
superoxide dismutase (SOD), glutathione (GSH) peroxidase, and catalase, as well as 
non-enzymatic ROS scavengers, vitamin E, vitamin C, and uric acid (Lykkesfeldt, Ha-
gen, Vinarsky, & Ames, 1998). Among all this, GSH is the most abundant and effective 
biological anti-oxidative reductant (Cross et al., 1997). ROS cause both oxidative da-
mage and elicit release of additional “inflamm-aging-cytokines” perpetuating a vicious 
cycle. Recently, it has been shown that ROS activation of toll-like receptors on a variety 
of immune cells play an important role in activating the inflammatory cascade (Gill, 
Tsung, & Billiar, 2010). Therefore, the continual presence of circulating pro-inflamma-
tory factors may keep the immune system in a state of chronic low-level activation and 
eventually this chronic immune activation causes immunosenesence.

Moreover, low-grade chronic inflammation has also been related to frailty, defined 
as an increased vulnerability to stress in old age (Hubbard, O'Mahony, Savva, Calver, 
& Woodhouse, 2009). Frailty results from the accumulation of functional declines in 
multiple systems that decrease overall physiological reserve leading to weight loss, 
especially loss of muscle, reduced strength and endurance, and overall poor physical 
function (Fried et al., 2001). Sarcopenia, one of the most noticeable changes occurring 
in elderly, is defined as the age-related loss of muscle mass, strength and function and 
is a major component of frailty and a risk factor for disability outcomes (Lang et al., 
2010). It has been shown by Visser et al. (2002) that older people with high cytokine 
levels (IL-6 and TNF-α) have a tendency to develop sarcopenia (Visser et al., 2002). 
In addition, a growing body of literature indicates that inflammatory processes are also 
related to cognitive decline and the development of dementia, including the vascular 
and Alzheimer’s types (Yaffe et al., 2003; Engelhart et al., 2004).

ACUTE EFFECTS OF EXERCISE

As aging is an inevitable process, there is a lot of interest in certain strategies that 
would reduce age-related inflammation and may therefore improve the quality of life in 
older adults. As such, there has been recent interest in the manipulation of certain life-
style factors like increasing physical activity levels, as a way of moderating the effects 
of aging on the immune system. Regular exercise is recommended for older people for 
a variety of reasons including increasing muscle mass and reducing risk for chronic 
diseases of the heart and metabolic systems. 

Acutely, exercise induces local and systemic cytokine responses in skeletal muscle. 
Effects of different types of exercise and different intensities on inflammation in in-
flammatory conditions were reviewed by Thomas (2013). Eccentric exercise causes 



ANNALES KINESIOLOGIAE • 8 • 2017 • 1

27

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

greater muscle damage than concentric and seems to be associated with higher inter-
leukine-6 expression, higher serum creatine kinase and greater recruitment of mono-
cytes, dendritic cells, and memory T cells to sites of infection and injury, although 
results vary due to differences in the participants' training status, exercise protocols and 
sampling times. Furthermore, exercise intensity governs the amount of the inflamma-
tory response that follows the exercise bout: while strenuous high-intensity exercise 
increases TNF-α level, low intensity exercise, if sustained over time, decreases TNF-α 
level (Thomas, 2013). In a study of acute effect of walking for four consecutive days at 
a self-selected pace for 30 km a day in twenty octogenarians, changes in immune cell 
numbers and functions were observed with an emphasis on response of CD4+ T cells, 
rather than CD8+ T cells or NK cells (van der Geest et al., 2017), with naïve CD4+ 
subsets dominating the CD4+ T cell compartment.

IMPACT OF CHRONIC PHYSICAL ACTIVITY ON INFLAMMATORY AND 
OXIDATIVE STATUS

It has been shown that lifelong physical activity is associated with increased life-
span, lower risk of functional and cognitive impairment, and lower levels of inflamma-
tory markers in older adults (Simpson & Guy, 2010). Exercise has also been reported to 
favorably impact immune function (Simpson & Guy, 2010). Repeated bouts of exercise 
seem to have a protective effect on the inflammatory response in patients with inflam-
matory conditions, which might have an important role in skeletal muscle adaptation 
(Thomas, 2013). Therefore, reducing inflamm-aging via exercise could be an efficient 
therapeutic approach to either prevent or delay the onset of those chronic diseases as-
sociated with low-grade chronic inflammation and thus reduce frailty and mortality in 
the elderly.

Some cross sectional studies have shown an association between low-grade inflam-
mation and physical inactivity in healthy older subjects (Pedersen & Bruusgard, 2003; 
Colbert et al., 2004). In our study of complete inactivity, we observed increased in-
flammation after 14 days of bed rest (Jurdana et al., 2015). The inflammatory response 
differed between elderly and young subjects: the elderly group responded to 14-days 
complete inactivity by pronounced increases in IL-6 and TNF-α while for the young 
subjects the TNF-α levels did not change and IL-6 levels decreased. Moreover, regu-
lar exercise training has been shown to reduce circulating levels of TNF-α, IL-6, and 
CRP in a population of healthy older adults (Colbert et al., 2004, Nicklas et al., 2008; 
Phillips, Flynn, McFarlin, Stewart, & Timmerman, 2010; Woods, Wilund, Martin, & 
Kistler, 2012).

The exact mechanism for reducing the levels of inflammatory markers by physical 
activity is not clear, but some possible mechanisms have been proposed for the anti-
-inflammatory effects of exercise (Gleeson et al., 2011). The anti-inflammatory effects 
of regular exercise may be mediated via reduction in visceral fat mass. Regular exercise 
reduces fat mass and AT inflammation, both known to contribute to systemic inflamma-



28

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

ANNALES KINESIOLOGIAE • 8 • 2017 • 1

tion (Calder et al., 2011). Independently of losses of fat mass, exercise also increases 
muscle production of IL-6. In contrast to what occurs in sepsis, contracting muscle 
produces IL-6 independently of TNF-α (there is, in fact, no TNF-α increase during 
exercise), which suggests the cytokine cascades in the contracting muscle are markedly 
different from those during infection (Pedersen & Febbraio, 2008). Exercise derived 
IL-6 is considered to possess a central role in anti-inflammatory activities and to be re-
sponsible for reducing TNF-α production – and increase anti-inflammatory cytokines, 
as for example anti-inflammatory adiponectin (Starkie, Ostrowski, Jauffred, Febbraio, 
& Pedersen, 2003). In addition, the anti-inflammatory effects of regular exercise may 
be mediated via increased production and release of anti-inflammatory cytokines, or 
reduced expression of toll-like receptors on monocytes and macrophages (Gleeson et 
al., 2011; Singh & Newman, 2011). Moreover, increases in antioxidant capabilities 
with regular exercise may prevent cellular DNA and structural damage from attacking 
ROS thus preventing premature biological aging of specific immune cells (Mota et al., 
2010). For example, it has been shown that proper physical exercise blunts the age-re-
lated decrease of GSH the body’s major anti-oxidative reductant (Carter at al., 2007).

As mentioned above, AD is also associated with chronic low-grade inflammati-
on. Physical activity influences inflammation, and both affect brain structure and AD. 
Indeed, higher levels of physical activity have been associated with al lower risk of 
developing AD (Luck et al., 2013). Although the main mechanism for this reduced risk 
is still unclear, physical activity may be associated with lower brain amyloid levels in 
humans (Liang et al., 2010; Head et al., 2012; Brown et al., 2013). Further, while ima-
ging techniques in humans showed that exercise positively correlated with brain-deri-
ved neurotrophic factor (a marker of adult neurogenesis), spatial memory, and various 
cognitive functions (Voss, Vivar, Kramer, & van Praag, 2013), enhanced neurogenesis 
due to exercise was directly shown in rodent studies (Voss et al, 2013).

Although it is possible that exercise as part of lifestyle acts to prevent or treat immu-
nosenescence, there is no clear answer to this question thus far. However, several inter-
ventions, including different types of exercises, have been proposed to restore immune 
function in elderly people. It has been shown that moderate exercise training might 
up-regulate monocytes and dendritic cells, thereby possibly improving T-cell mediated 
immunity in elderly (Shimizu et al., 2008; Schimizu et al., 2011). Moreover, it has been 
shown, that regular exercise is associated with improved immune responsiveness to 
influenza vaccination in elderly (Kohut & Senchina, 2004; Woods et al., 2009). Thus, 
the accumulated data thus far suggest that exercise may be a powerful approach to re-
storing immune function in elderly people.

CONCLUSIONS

Taken together, we conclude that physical activity, such as regular exercise, activa-
tes the release of hormones, myokines and cytokines, as well as modulates the expres-
sion of various immune-reactive molecules, which all contribute to anti-inflammatory 



ANNALES KINESIOLOGIAE • 8 • 2017 • 1

29

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

effects and possible the attenuation of immunosenescence. Moreover, the reduction of 
visceral fat mass alone already leads to a decreased production and release of pro-in-
flammatory adipokines from fat tissue. Therefore, lifestyle attitudes, particularly aero-
bic exercise in the elderly may provide low cost and long-term ways to limit inflamma-
tion and slow declines in the elderly.

REFERENCES

Arnold, C. R., Wolf, J., Brunner, S., Herndler-Brandstetter, D., & Grubeck-Loeben-
stein, B. (2011). Gain and loss of T cell subsets in old age--age-related reshaping of the 
T cell repertoire. Journal of Clinical Immunology, 31(2), 137-146. doi 10.1007/s10875-
010-9499-x. VIEW ITEM

Brown, B. M., Peiffer, J. J., Taddei, K., Lui, J. K., Laws, S. M., Gupta, V. B., … Mar-
tins, R. N. (2013). Physical activity and amyloid-β plasma and brain levels: results from 
the Australian Imaging, Biomarkers and Lifestyle Study of Ageing. Molecular Psychia-
try, 18(8), 875-881. doi:10.1038/mp.2012.107. VIEW ITEM

Bruunsgaard, H. (2006). The clinical impact of systemic low-level inflammation in elderly 
populations. With special reference to cardiovascular disease, dementia and mortality. 
Danish Medical Bulletin, 53(3), 285-309.

Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., 
… Winklhofer-Roob, B. M. (2011). Dietary factors and low-grade inflammation in 
relation to overweight and obesity. British Journal of Nutrition, 106(3), S5-S78. doi: 
10.1017/S0007114511005460. VIEW ITEM

Cannizzo, E. S., Clement, C. C., Sahu, R., Follo, C., & Santambrogio, L. (2011). Oxida-
tive stress, inflamm-aging and immunosenescence. Journal of Proteomics, 74(11), 2313-
2323. doi: 10.1016/j.jprot.2011.06.005. VIEW ITEM

Carter, C. S., Hofer, T., Seo, A. Y., & Leeuwenburgh, C. (2007). Molecular mechanisms 
of life- and health-span extension: role of calorie restriction and exercise intervention. 
Applied Physiology, Nutrition and Metabolism, 32(5), 954-966. doi: 10.1139/H07-085. 
VIEW ITEM

Chung, H. Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A. Y., ... Leeu-
wenburgh, C. (2009). Molecular inflammation: underpinnings of aging and age-related 
diseases. Ageing Research Reviews, 8(1), 18-30. doi: 10.1016/j.arr.2008.07.002. VIEW 
ITEM

Colbert, L. H., Visser, M., Simonsick, E. M., Tracy, R. P., Newman, A. B., Kritchevsky, 
S. B., … Harris, T. B. (2004). Physical activity, exercise, and inflammatory markers in 
older adults: findings from the Health, Aging and Body Composition Study. Journal of the 
American Geriatric Society, 52(7), 1098-1104. doi: 10.1111/j.1532-5415.2004.52307.x. 
VIEW ITEM

Cross, C. E., Hasegawa, G., Reddy, K. A., & Omaye, S. T. (1977). Enhanced lung toxicity 
of O2 in selenium-deficient rats. Research Communications in Chemical Pathology and 
Pharmacology, 16(4), 695-706.

De Martinis, M., Franceschi, C., Monti, D., & Ginaldi, L. (2005). Inflamm-ageing and 
lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Let-
ters, 579(10), 2035-2039. doi: 10.1016/j.febslet.2005.02.055. VIEW ITEM

http://www.ncbi.nlm.nih.gov/pubmed/?term=arnold+wolf+brunner
https://doi.org/10.1007/s10875-010-9499-x
http://www.ncbi.nlm.nih.gov/pubmed?term=Laws%20SM%5BAuthor%5D&cauthor=true&cauthor_uid=22889922
http://www.ncbi.nlm.nih.gov/pubmed?term=Gupta%20VB%5BAuthor%5D&cauthor=true&cauthor_uid=22889922
http://www.ncbi.nlm.nih.gov/pubmed/22889922
http://www.ncbi.nlm.nih.gov/pubmed/22889922
https://doi.org/10.1038/mp.2012.107
http://www.ncbi.nlm.nih.gov/pubmed/?term=bruunsgard+the+clinical+impact
http://www.ncbi.nlm.nih.gov/pubmed/22133051
http://www.ncbi.nlm.nih.gov/pubmed/22133051
https://doi.org/10.1017/S0007114511005460
https://doi.org/10.1016/j.jprot.2011.06.005
http://www.ncbi.nlm.nih.gov/pubmed/?term=carter+hofer+seo
https://doi.org/10.1139/H07-085
http://www.ncbi.nlm.nih.gov/pubmed?term=Carter%20C%5BAuthor%5D&cauthor=true&cauthor_uid=18692159
http://www.ncbi.nlm.nih.gov/pubmed/?term=chung+cesari+anton+inflammation
https://doi.org/10.1016/j.arr.2008.07.002
https://doi.org/10.1016/j.arr.2008.07.002
http://www.ncbi.nlm.nih.gov/pubmed/15209647
http://www.ncbi.nlm.nih.gov/pubmed/15209647
https://doi.org/10.1111/j.1532-5415.2004.52307.x
http://www.ncbi.nlm.nih.gov/pubmed/860085
http://www.ncbi.nlm.nih.gov/pubmed/860085
https://doi.org/10.1016/j.febslet.2005.02.055


30

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

ANNALES KINESIOLOGIAE • 8 • 2017 • 1

Engelhart, M. J., Geerlings, M. I., Meijer, J., Kiliaan, A., Ruitenberg, A., van Swi-
eten, J. C., ... Breteler, M. M. B. (2004). Inflammatory proteins in plasma and the risk 
of dementia: the rotterdam study. Archives of Neurology, 61(5), 668-672. doi:10.1001/
archneur.61.5.668. VIEW ITEM

Franceschi, C., Bonafè, M., & Valensin, S. (2000). Human immunosenescence: the pre-
vailing of innate immunity, the failing of clonotypic immunity, and the filling of immu-
nological space. Vaccine, 18(16), 1717-1720. doi: 10.1016/S0264-410X(99)00513-7. 
VIEW ITEM

Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., ... 
McBurnie, M. A. (2001). Frailty in older adults: evidence for a phenotype. The journals 
of gerontology. Series A, Biological sciences and medical sciences, 56(3). M146-m157. 
doi: 10.1093/gerona/56.3.M146. VIEW ITEM

Gill, R., Tsung, A., & Billiar, T. (2010). Linking oxidative stress to inflammation: Toll-
like receptors. Free Radical Biology and Medicine, 48(9), 1121-1132. doi: 10.1016/j.
freeradbiomed.2010.01.006. VIEW ITEM

Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S., & Nimmo, M. 
A. (2011). The anti-inflammatory effects of exercise: mechanisms and implications for 
the prevention and treatment of disease. Nature Reviews Immunology, 11(9), 607-615. 
doi:10.1038/nri3041. VIEW ITEM

Gruver, A. L., Hudson, L. L., & Sempowski, G. D. (2007). Immunosenescence of ageing. 
The Journal of Pathology, 211(2), 144-156. doi: 10.1002/path.2104. VIEW ITEM

Head, D., Bugg, J. M., Goate, A. M., Fagan, A. M., Mintun, M. A., Benzinger, T., ... 
Morris, J. C. (2012). Exercise engagement as a moderator of the effects of APOE geno-
type on amyloid deposition. Archives of Neurology, 69(5), 636-643. doi:10.1001/arch-
neurol.2011.845. VIEW ITEM

Hubbard, R. E., O’Mahony, M. S., Savva, G. M., Calver, B. L., & Woodhouse, K. W. 
(2009). Inflammation and frailty measures in older people. Journal of Cellular and Mo-
lecular Medicine, 13(9B), 3103-3109. doi: 10.1111/j.1582-4934.2009.00733.x. VIEW 
ITEM

Jurdana, M., Jenko-Pražnikar, Z., Mohorko, N., Petelin, A., Jakus, T., Šimunič, B., 
Pišot, R. (2015). Impact of 14-day bed rest on serum adipokines and low-grade inflam-
mation in younger and older adults. Age, 37(6), 116. doi: 10.1007/s11357-015-9848-z. 
VIEW ITEM

Jylhä, M., Paavilainen, P., Lehtimäki, T., Goebeler, S., Karhunen, P. J., Hervonen, A., 
& Hurme, M. (2007). Interleukin-1 receptor antagonist, interleukin-6, and C-reactive 
protein as predictors of mortality in nonagenarians: the vitality 90+ study. The journals 
of gerontology. Series A, Biological sciences and medical sciences, 62(9), 1016-1021. 
doi: 10.1093/gerona/62.9.1016. VIEW ITEM

Knight, J. A. (2011). Diseases and disorders associated with excess body weight. Annals of 
Clinical & Laboratory Science, 41(2), 107-121. VIEW ITEM

Kohut, M. L., & Senchina, D. S. (2004). Reversing age-associated immunosenescence via 
exercise. Exercise Immunology Review, 10, 6-41. 

Kregel, K. C., & Zhang, H. J. (2007). An integrated view of oxidative stress in aging: ba-
sic mechanisms, functional effects, and pathological considerations. American Journal 
of Physiology, Regulatory, Integrative and Comparative Physiology, 292(1), R18-R36. 
doi: 10.1152/ajpregu.00327.2006. VIEW ITEM

http://www.ncbi.nlm.nih.gov/pubmed/15148142
https://doi.org/10.1001/archneur.61.5.668
http://www.ncbi.nlm.nih.gov/pubmed/10689155
https://doi.org/10.1016/S0264-410X(99)00513-7
https://doi.org/10.1093/gerona/56.3.M146
http://www.ncbi.nlm.nih.gov/pubmed/?term=Gill+R%2C+Tsung+A+and+Billiar+T+(2010).+Linking+oxidative+stress+to+inflammation%3A+Toll-like+receptors.+Free+radical+biology+%26+medicine%2C+48%3A+1121-1132
https://doi.org/10.1016/j.freeradbiomed.2010.01.006
http://www.ncbi.nlm.nih.gov/pubmed/21818123
https://doi.org/10.1038/nri3041
http://www.ncbi.nlm.nih.gov/pubmed/?term=gruver+hudson+sempowski
https://doi.org/10.1002/path.2104
http://www.ncbi.nlm.nih.gov/pubmed/22232206
https://doi.org/10.1001/archneurol.2011.845
http://www.ncbi.nlm.nih.gov/pubmed/19438806
http://www.ncbi.nlm.nih.gov/pubmed/19438806
https://doi.org/0.1111/j.1582-4934.2009.00733.x
https://doi.org/0.1111/j.1582-4934.2009.00733.x
https://doi.org/10.1007/s11357-015-9848-z
https://doi.org/10.1093/gerona/62.9.1016
http://www.ncbi.nlm.nih.gov/pubmed/?term=Knight+2011+AND+diseases+and+disorders+associated+with+excess+body+weight
http://www.ncbi.nlm.nih.gov/pubmed/?term=Knight+2011+AND+diseases+and+disorders+associated+with+excess+body+weight
http://www.annclinlabsci.org/content/41/2/107.full.pdf+html
http://www.ncbi.nlm.nih.gov/pubmed/15633584
http://www.ncbi.nlm.nih.gov/pubmed/?term=Kregel+and+Zhang+AND+2007+AND+ROS+AND+aging
http://www.ncbi.nlm.nih.gov/pubmed/?term=Kregel+and+Zhang+AND+2007+AND+ROS+AND+aging
https://doi.org/10.1152/ajpregu.00327.2006


ANNALES KINESIOLOGIAE • 8 • 2017 • 1

31

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

Lang, T., Streeper, T., Cawthon, P., Baldwin, K., Taaffe, D. R., & Harris, T. B. (2010). 
Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporosis 
International, 21(4), 543-559. doi: 10.1007/s00198-009-1059-y. VIEW ITEM

Liang, K. Y., Mintun, M. A., Fagan, A. M., Goate, A. M., Bugg, J. M., Holtzman, D. M., 
… Head, D. (2010). Exercise and Alzheimer’s disease biomarkers in cognitively nor-
mal older adults. Annals of Neurology, 68(3), 311-318. doi: 10.1002/ana.22096. VIEW 
ITEM

Luck, T., Riedel-Heller, S. G., Luppa, M., Wiese, B., Köhler, M., Jessen, F., ... Mai-
er, W. (2013). Apolipoprotein E epsilon 4 genotype and a physically active lifestyle 
in late life: analysis of gene-environment interaction for the risk of dementia and Al-
zheimer’s disease dementia. Psychological Medicine, 44(6), 1319-1329. doi: 10.1017/
S0033291713001918. VIEW ITEM

Lykkesfeldt, J., Hagen, T. M., Vinarsky, V., & Ames, B. N. (1998). Age-associated de-
cline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--re-
versal with (R)-alpha-lipoic acid supplementation. FASEB Journal, 12(12), 1183-1189. 
VIEW ITEM

Mota, M. P., Peixoto, F. M., Soares, J. F., Figueiredo, P. A., Leitão, J. C., Gaivão, I., 
& Duarte, J. A. (2010). Influence of aerobic fitness on age-related lymphocyte DNA 
damage in humans: relationship with mitochondria respiratory chain and hydrogen pe-
roxide production. Age, 32(3), 337-346. doi 10.1007/s11357-010-9138-8. VIEW ITEM

Müller, L., & Pawelec, G. (2014). Aging and immunity - Impact of behavioral intervention. 
Brain Behavour and Immunity, 39, 8-22. doi: 10.1016/j.bbi.2013.11.015. VIEW ITEM

Nguyen, V., Mendelsohn, A., & Larrick, J. W. (2017). Interleukin-7 and Immunosene-
scence. Journal of Immunology Research, 2017:4807853. doi: 10.1155/2017/4807853. 
VIEW ITEM

Nicklas, B. J., Hsu, F. C., Brinkley, T. J., Church, T., Goodpaster, B. H., Kritchevsky, 
S. B., & Pahor, M. (2008). Exercise training and plasma C-reactive protein and interle-
ukin-6 in elderly people. Journal of the American Geriatric Society, 56(11), 2045-2052. 
doi: 10.1111/j.1532-5415.2008.01994.x. VIEW ITEM

Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011). Adipokines in inflamma-
tion and metabolic disease. Nature Reviews Immunology, 11(2), 85-97. doi:10.1038/
nri2921. VIEW ITEM

Pedersen, B. K., & Bruunsgaard, H. (2003). Possible beneficial role of exercise in mo-
dulating low-grade inflammation in the elderly. Scandinavian Journal of Medicine & 
Science in Sports, 13(1), 56-62. doi: 10.1034/j.1600-0838.2003.20218.x. VIEW ITEM

Pedersen, B. K., & Febbraio, M. A. (2008). Muscle as an endocrine organ: focus on 
muscle-derived interleukin-6. Physiological Review, 88(4), 1379-1406. doi: 10.1152/
physrev.90100.2007. VIEW ITEM

Phillips, M. D., Flynn, M. G., McFarlin, B. K., Stewart, L. K., & Timmerman, K. L. 
(2010). Resistance training at eight-repetition maximum reduces the inflammatory mili-
eu in elderly women. Medicine and Science in Sports & Exercise, 42(2), 314-325. doi: 
10.1249/MSS.0b013e3181b11ab7. VIEW ITEM

Shimizu, K., Kimura, F., Akimoto, T., Akama, T., Tanabe, K., Nishijima, T., … Kono, 
I. (2008). Effect of moderate exercise training on T-helper cell subpopulations in elderly 
people. Exercise Immunology Review, 14, 24-37.

Shimizu, K., Suzuki, N,. Imai, T., Aizawa, K., Nanba, H., Hanaoka, Y., … Akama, 
T. (2011). Monocyte and T-cell responses to exercise training in elderly subjects. 

http://www.ncbi.nlm.nih.gov/pubmed/?term=Streeper+AND+sarcopenia
http://www.ncbi.nlm.nih.gov/pubmed/?term=Streeper+AND+sarcopenia
https://doi.org/10.1007/s00198-009-1059-y
http://www.ncbi.nlm.nih.gov/pubmed/?term=liang+mintun+fagan
https://doi.org/10.1002/ana.22096
https://doi.org/10.1002/ana.22096
http://www.ncbi.nlm.nih.gov/pubmed/23883793
https://doi.org/10.1017/S0033291713001918
http://www.ncbi.nlm.nih.gov/pubmed/9737721
http://www.fasebj.org/content/12/12/1183.full
http://www.ncbi.nlm.nih.gov/pubmed/20640548
https://doi.org/10.1007/s11357-010-9138-8
https://doi.org/10.1016/j.bbi.2013.11.015
https://doi.org/10.1155/2017/4807853
http://www.ncbi.nlm.nih.gov/pubmed/19016938
https://doi.org/10.1111/j.1532-5415.2008.01994.x
http://www.ncbi.nlm.nih.gov/pubmed/21252989
https://doi.org/10.1038/nri2921
http://www.ncbi.nlm.nih.gov/pubmed/12535318
http://www.ncbi.nlm.nih.gov/pubmed/12535318
https://doi.org/10.1034/j.1600-0838.2003.20218.x
https://doi.org/10.1152/physrev.90100.2007
https://doi.org/10.1249/MSS.0b013e3181b11ab7
http://www.ncbi.nlm.nih.gov/pubmed/19203082


32

Ana PETELIN, Nina MOHORKO: EXERCISE AND THE AGEING IMMUNE SYSTEM ..., 23–32

ANNALES KINESIOLOGIAE • 8 • 2017 • 1

The Journal of Strength & Conditioning Research, 25(9), 2565-2572. doi: 10.1519/
JSC.0b013e3181fc5e67. VIEW ITEM

Simpson, R. J., & Guy, K. (2010). Coupling aging immunity with a sedentary lifestyle: has 
the damage already been done? Gerontology, 56(5), 449-458. doi: 10.1159/000270905. 
VIEW ITEM

Singh, T., & Newman, A. B. (2011). Inflammatory markers in population studies of ag-
ing. Ageing Research Reviews, 10(3), 319-329. doi: 10.1016/j.arr.2010.11.002. VIEW 
ITEM

Starkie, R., Ostrowski, S. R., Jauffred, S., Febbraio, M., & Pedersen, B. K. (2003). 
Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. 
FASEB Journal, 17(8), 884-886. doi: 10.1096/fj.02-0670fje. VIEW ITEM

Thomas, J. L. (2013). Helpful or harmful? Potential effects of exercise on select inflamma-
tory conditions. Physician Sportsmed, 41(4), 93-100. doi: 10.3810/psm.2013.11.2040. 
VIEW ITEM

van der Geest, K. S. M., Wang, Q., Eijsvogels, T. M. H., Koenen, H. J. P., Joosten, I., 
Brouwer, E., … Boots, A. M. H. (2017). Changes in peripheral immune cell numbers 
and functions in octogenarian walkers - an acute exercise study. Immunity & ageing. 
14(5). doi: 10.1186/s12979-017-0087-2. VIEW ITEM

Vasto, S., Candore, G., Balistreri, C. R., Caruso, M., Colonna-Romano, G., Grimaldi, 
M. P., … Caruso, C. (2007). Inflammatory networks in ageing, age-related diseases 
and longevity. Mechanism of Ageing and Development, 128(1), 83-91. doi: 10.1016/j.
mad.2006.11.015. VIEW ITEM

Visser, M., Pahor, M., Taaffe, D. R., Goodpaster, B. H., Simonsick, E. M., Newman, A. 
B., … Harris, T. B. (2002). Relationship of interleukin-6 and tumor necrosis factor-al-
pha with muscle mass and muscle strength in elderly men and women: the Health ABC 
Study.  The journals of gerontology. Series A, Biological sciences and medical sciences, 
57(5), M326-332. doi: 10.1093/gerona/57.5.M326. VIEW ITEM

Voss, M. W., Vivar, C., Kramer, A. F., & van Praag, H. (2013). Bridging animal and hu-
man models of exercise-induced brain plasticity. Trends in Cognitive Sciences, 17(10), 
525-544. doi: 10.1016/j.tics.2013.08.001. VIEW ITEM

Woods, J. A., Keylock, K. T., Lowder, T., Vieira, V. J., Zelkovich, W., Dumich, S., 
… McAuley, E. (2009). Cardiovascular exercise training extends influenza vac-
cine seroprotection in sedentary older adults: the immune function intervention trial. 
Journal of the American Geriatric Society, 57(12), 2183-2191. doi: 10.1111/j.1532-
5415.2009.02563.x. VIEW ITEM

Woods, J. A., Wilund, K. R., Martin, S. A., & Kistler, B. M. (2012). Exercise, inflamma-
tion and aging. Aging and Disease, 3(1), 130-140. VIEW ITEM

Yaffe, K., Lindquist, K., Penninx, B. W., Simonsick, E. M., Pahor, M., Kritchevsky, 
S., … Harris, T. (2003). Inflammatory markers and cognition in well-function-
ing African-American and white elders. Neurology, 61(1), 76-80. doi: 10.1212/01.
WNL.0000073620.42047.D7. VIEW ITEM

Xia, S., Zhang, X., Zheng, S., Khanabdali, R., Kalionis, B., Wu, J., … Tai, X. (2016). An 
update on inflamm-aging: mechanisms, prevention, and treatment. Journal of Immunol-
ogy Research, 2016:8426874. doi: 10.1155/2016/8426874. VIEW ITEM

https://doi.org/10.1519/JSC.0b013e3181fc5e67
http://www.ncbi.nlm.nih.gov/pubmed/20029165
https://doi.org/10.1159/000270905
https://doi.org/10.1016/j.arr.2010.11.002
https://doi.org/10.1016/j.arr.2010.11.002
http://www.ncbi.nlm.nih.gov/pubmed/12626436
https://doi.org/10.1096/fj.02-0670fje
http://dx.doi.org/10.3810/psm.2013.11.2040
https://doi.org/10.1186/s12979-017-0087-2
http://www.ncbi.nlm.nih.gov/pubmed/17118425
https://doi.org/10.1016/j.mad.2006.11.015
http://www.ncbi.nlm.nih.gov/pubmed/11983728
https://doi.org/10.1093/gerona/57.5.M326
https://doi.org/10.1016/j.tics.2013.08.001
http://www.ncbi.nlm.nih.gov/pubmed/20121985
http://onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2009.02563.x/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320801/pdf/ad-3-1-130.pdf
http://dx.doi.org/10.1212/01.WNL.0000073620.42047.D7
http://dx.doi.org/10.1155/2016/8426874

	_GoBack
	_GoBack
	_GoBack
	_Hlk501362470
	_Hlk501363405
	_Hlk501369360

