Skip to main content

Advertisement

SpringerLink
Log in

Effects of aerobic training on markers of autophagy in the elderly

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Autophagy is a molecular process essential for the maintenance of cellular homeostasis, which appears to (i) decline with age and (ii) respond to physical exercise. In addition, recent evidence suggests a crosstalk between autophagy and toll-like receptor (TLR)-associated inflammatory responses. This study assessed the effects of aerobic exercise training on autophagy and TLR signaling in older subjects. Twenty-nine healthy women and men (age, 69.7 ± 1.0 year) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week aerobic training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and protein levels of protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1), beclin-1, phosphorylated unc-51-like kinase (ULK-1), ubiquitin-like autophagy-related (Atg)12, Atg16, and lysosome-associated membrane protein (LAMP)-2 were measured. TLR2 and TLR4 signaling pathways were also analyzed. Peak oxygen uptake increased in TG after the intervention. Protein expression of beclin-1, Atg12, Atg16, and the LC3II/I ratio increased following the training program (p < 0.05), while expression of p62/SQSTM1 and phosphorylation of ULK-1 at Ser757 were lower (p < 0.05). Protein content of TLR2, TLR4, myeloid differentiation primary response gen 88 (MyD88), and TIR domain-containing adaptor-inducing interferon (TRIF) were not significantly modified by exercise. The current data indicate that aerobic exercise training induces alterations in multiple markers of autophagy, which seem to be unrelated to changes in TLR2 and TLR4 signaling pathways. These results expand knowledge on exercise-induced autophagy adaptations in humans and suggest that the exercise type employed may be a key factor explaining the potential relationship between autophagy and TLR pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Barth S, Glick D, Macleod KF (2010) Autophagy: assays and artifacts. J Pathol 221:117–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bayod S, Del Valle J, Pelegri C, Vilaplana J, Canudas AM, Camins A, et al. (2014) Macroautophagic process was differentially modulated by long-term moderate exercise in rat brain and peripheral tissues. J Physiol Pharmacol 65:229–239

    CAS  PubMed  Google Scholar 

  • Bonilla DL, Bhattacharya A, Sha Y, Xu Y, Xiang Q, Kan A, Jagannath C, Komatsu M, Eissa NT (2013) Autophagy regulates phagocytosis by modulating the expression of scavenger receptors. Immunity 39:537–547

    Article  CAS  PubMed  Google Scholar 

  • Choi AM, Ryter SW, Levine B (2013) Autophagy in human health and disease. N Engl J Med 368:651–662

    Article  CAS  PubMed  Google Scholar 

  • Cuervo AM, Macian F (2014) Autophagy and the immune function in aging. Curr Opin Immunol 29:97–104

    Article  CAS  PubMed  Google Scholar 

  • Cuevas MJ, Almar M, García-Glez JC, García-López D, De Paz JA, Alvear-Ordenes I, et al. (2005) Changes in oxidative stress markers and NF-kappaB activation induced by sprint exercise. Free Radic Res 39:431–439

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Gonzalo R, De Paz JA, Rodriguez-Miguelez P, Cuevas MJ, González-Gallego J (2012) Effects of eccentric exercise on toll-like receptor 4 signaling pathway in peripheral blood mononuclear cells. J Appl Physiol 112:2011–2018

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Gonzalo R, De Paz JA, Rodriguez-Miguelez P, Cuevas MJ, González-Gallego J (2014) TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women. Mediat Inflamm 2014:479395

    Article  Google Scholar 

  • Gleeson M, McFarlin B, Flynn M (2006) Exercise and toll-like receptors. Exerc Immunol Rev 12:34–53

    PubMed  Google Scholar 

  • He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, Loh J, Fisher J, et al. (2012) Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 481:511–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang J, Xu J, Pang S, Bai B, Yan B (2012) Age-related decrease of the LAMP-2 gene expression in human leukocytes. Clin Biochem 45:1229–1232

    Article  CAS  PubMed  Google Scholar 

  • Into T, Inomata M, Niida S, Murakami Y, Shibata K (2010) Regulation of MyD88 aggregation and the MyD88-dependent signaling pathway by sequestosome 1 and histone deacetylase 6. J Biol Chem 285:35759–35769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Into T, Inomata M, Takayama E, Takigawa T (2012) Autophagy in regulation of toll-like receptor signaling. Cell Signal 24:1150–1162

    Article  CAS  PubMed  Google Scholar 

  • Jamart C, Francaux M, Millet GY, Deldicque L, Frère D, Féasson L (2012) Modulation of autophagy and ubiquitin–proteasome pathways during ultra-endurance running. J Appl Physiol 112:1529–1537

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Kundu M, Viollet B, Kam KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of ULK-1. Nat Cell Biol 13:132–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim YA, Kim YS, Oh SL, Kim HJ, Song W (2013) Autophagic response to exercise training in skeletal muscle with age. J Physiol Biochem 69:697–705

    Article  CAS  PubMed  Google Scholar 

  • Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al. (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Miao W, Ma J, Xv Z, Bo H, Li J, et al. (2016) Acute exercise-induced mithochondrial stress triggers an inflammatory responses in the myocardium via NLRP3 inflammasome activation with mitophagy. Oxidative Med Cell Longev. doi:10.1155/2016/1987149

    Google Scholar 

  • Lira VA, Okutsu M, Zhang M, Greene NP, Laker RC, Breen DS, et al. (2013) Autophagy is required for exercise training induced skeletal muscle adaptation and improvement of physical performance. FASEB J 27:4184–4193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217

    Article  PubMed  PubMed Central  Google Scholar 

  • Luo L, Lu AM, Wang Y, Hong A, Chen Y, Hu J, et al. (2013) Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, akt/mTOR and akt/FOXO3a signaling in aged rats. Exp Gerontol 48:427–436

    Article  CAS  PubMed  Google Scholar 

  • Moller AB, Vendelbo MH, Christensen B, Clasen BF, Bak AM, Jørgensen JO, et al. (2015) Physical exercise increases autophagic signaling through ULK-1 in human skeletal muscle. J Appl Physiol 118:971–979

    Article  PubMed  Google Scholar 

  • Nakatogawa H, Ichimura Y, Ohsumi Y (2007) Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130:165–178

    Article  CAS  PubMed  Google Scholar 

  • Netea-Maier RT, Plantinga TS, Van De Veerdonk FL, Smit JW, Netea MG (2015) Modulation of inflammation by autophagy: consequences for human disease. Autophagy. doi:10.1080/15548627.2015.1071759

    PubMed  Google Scholar 

  • Nickel T, Hanssen H, Emslander I, Drexel V, Hertel G, Schmidt-Trucksass A, et al. (2011) Immunomodulatory effects of aerobic training in obesity. Mediat Inflamm 2011:308965

    Article  Google Scholar 

  • Oh JE, Lee HK (2013) Autophagy as an immune modulator. Immun Netw 13:1–9

    Article  Google Scholar 

  • Pagano AF, Py G, Bernardi H, Candau RB, Sanchez AM (2014) Autophagy and protein turnover signaling in slow-twitch muscle during exercise. Med Sci Sports Exerc 46:1314–1325

    Article  CAS  PubMed  Google Scholar 

  • Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, et al. (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131–24145

    Article  CAS  PubMed  Google Scholar 

  • Peeri M, Amiri S (2015) Protective effects of exercise in metabolic disorders are mediated by inhibition of mitochondrial-derived sterile inflammation. Med Hypotheses 85:707–709

    Article  CAS  PubMed  Google Scholar 

  • Reyna SM, Tantiwong P, Cersosimo E, Defronzo RA, Sriwijitkamol A, Musi N (2013) Short-term exercise training improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells from insulin-resistant subjects. J Diabetes Res 2013:107805

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodriguez-Miguélez P, Fernandez-Gonzalo R, Almar M, Mejías Y, Rivas A, de Paz JA, et al. (2014) Role of toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects. Age (Dordr) 36:9734

    Article  Google Scholar 

  • Rodriguez-Miguelez P, Fernandez-Gonzalo R, Collado PS, Almar M, Martinez-Florez S, de Paz JA, et al. (2015) Whole-body vibration improves the anti-inflammatory status in elderly subjects through toll-like receptor 2 and 4 signaling pathways. Mech Ageing Dev 150:12–19

    Article  CAS  PubMed  Google Scholar 

  • Sanchez AM, Bernardi H, Py G, Candau RB (2014) Autophagy is essential to support skeletal muscle plasticity in response to endurance exercise. Am J Physiol Regul Integr Comp Physiol 307:R956–R969

    Article  CAS  PubMed  Google Scholar 

  • San-Miguel B, Crespo I, Sanchez DI, González-Fernández B, Ortiz de Urbina J, Tuñón MJ, et al. (2015) Melatonin inhibits autophagy and endoplasmic reticulum stress in mice with carbon tetrachloride-induced fibrosis. J Pineal Res 59:151–162

    Article  CAS  PubMed  Google Scholar 

  • San-Miguel B, Crespo I, Vallejo D, Ortiz de Urbina J, Álvarez M, Tuñón MJ, et al. (2014) Melatonin modulates the autophagic response in acute liver failure induced by the rabbit hemorrhagic disease virus. J Pineal Res 56:313–321

    Article  CAS  PubMed  Google Scholar 

  • Schwalm C, Jamart C, Benoit N, Naslain D, Premont C, Prevet J, et al. (2015) Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation. FASEB J 29:3515–3526

    Article  CAS  PubMed  Google Scholar 

  • Shi CS, Shenderov K, Huang NN, Kabat J, Abu-Asab M, Fitzgerald KA, Sher A, Kehrl JH (2012) Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 13:255–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tam BT, Siu PM (2014) Autophagic cellular responses to physical exercise in skeletal muscle. Sports Med 44:625–640

    Article  PubMed  Google Scholar 

  • Tam BT, Pei XM, Yu AP, Sin TK, Leung KK, Au KK, et al. (2015) Autophagic adaptation is associated with exercise-induced fibre-type shifting in skeletal muscle. Acta Physiol 214:221–236

    Article  CAS  Google Scholar 

  • Vainshtein A, Grumati P, Sandri M, Bonaldo P (2014) Skeletal muscle, autophagy, and physical activity: the ménage à trois of metabolic regulation in health and disease. J Mol Med (Berl) 92:127–137

    Article  CAS  Google Scholar 

  • Walczak M, Martens S (2013) Dissecting the role of the Atg12–Atg5–Atg16 complex during autophagosome formation. Autophagy 9:424–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weng TP, Huang SC, Chuang YF, Wang JS (2013) Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men. PLoS One 13:e80248

    Article  Google Scholar 

  • Wohlgemuth SE, Lees HA, Marzetti E, Manini TM, Aranda JM, Daniels MJ (2011) An exploratory analysis of the effects of a weight loss plus exercise program on cellular quality control mechanisms in older overweight women. Rejuvenation Res 14:315–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C (2010) Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol 45:138–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao J, Braultt JJ, Schild A, Cao P, Sandri M, Schiaffino S, et al. (2007) FoxO3 coordinately activates protein degradation by the autophagy/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 6:472–483

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Plan Nacional I + D + I DEP2013-47659-R, Spain. YM is a fellow from the University de Los Andes, Venezuela.

Author information

Authors and Affiliations

  1. Institute of Biomedicine (IBIOMED), University of León, Campus Vegazana s/n, 24071, León, Spain

    Yubisay Mejías-Peña, Susana Martínez-Flórez, Mar Almar, José A. de Paz, María J. Cuevas & Javier González-Gallego

  2. Divisions of Clinical and Translational Sciences, Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, USA

    Paula Rodriguez-Miguelez

  3. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Rodrigo Fernandez-Gonzalo

Authors
  1. Yubisay Mejías-Peña
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paula Rodriguez-Miguelez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rodrigo Fernandez-Gonzalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susana Martínez-Flórez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mar Almar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José A. de Paz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. María J. Cuevas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Javier González-Gallego
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Javier González-Gallego.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mejías-Peña, Y., Rodriguez-Miguelez, P., Fernandez-Gonzalo, R. et al. Effects of aerobic training on markers of autophagy in the elderly. AGE 38, 33 (2016). https://doi.org/10.1007/s11357-016-9897-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11357-016-9897-y

Keywords

Search

Navigation