Exercise attenuates the major hallmarks of aging

Abstract

Regular exercise has multi-system anti-aging effects. Here we summarize how exercise impacts the major hallmarks of aging. We propose that, besides searching for novel pharmaceutical targets of the aging process, more research efforts should be devoted to gaining insights into the molecular mediators of the benefits of exercise and to implement effective exercise interventions for elderly people.

FIG. 1.

Summary of the main anti-aging effects of regular exercise vs. aging effects at the multi-systemic (left; see Chodzko-Zajko et al. for an in-depth review) and cellular level (right; see text). AKT, protein kinase B; AMPK, AMP-activated protein kinase; ASC, apoptosis-associated speck-like protein caspase; AUF1, AU-binding factor 1; BDNF, brain-derived neurotrophic factor; FoxO3a, human protein encoded by the FOXO3 gene; Glut 4, glucose transporter type 4; HATs, histone acetyltransferases; HDACs, histone deacetylases; HRV, heart rate variability; IGF-1, insulin-like growth factor 1; IL, interleukin; jmjC, jumonji C proteins; LSD, lysine-specific histone demethylase; miR, micro-RNA; mtDNA, mitochondrial DNA; mTOR, mammalian target of rapamycin; NK cell, natural killer cell; NLRP3, NOD-like receptor protein 3; PBMCs, peripheral blood mononucleated cells; PDK4, pyruvate dehydrogenase kinase isoenzyme 4; PGC-1, peroxisome proliferator-activated receptor gamma coactivator 1; PPAR-δ, peroxisome proliferator-activated receptor δ; PTMs, post-translational modifications; Qmax, maximal cardiac output; ROM, range of motion; SIRT, sirtuin; TERT, human telomerase reverse transcriptase. Color images available online at www.liebertpub.com/rej

FIG. 2.

Main signaling pathways involved in the exercise effects in the skeletal muscle tissue. 4E-BP1, eukaryotic translation initiation factor 4E (eIF4E) binding protein; AKT, protein kinase B; AMP, adenosine monophosphate; AMPK, AMP activated protein kinase; ATF2, activating transcription factor 2; ATP, adenosine triphosphate; CaMKII, calmodulin-dependent protein kinase II; CREB, cAMP response-element-binding protein; ERK1/2, extracellular signal-regulated kinase 1 and 2; FAK, focal adhesion kinase; FoxO1, human protein encoded by the FOXO gene; FOXOs, Forkhead box-O transcription factors; HDACs, histone deacetylases; HIF, hypoxia-inducible factor; JNK, c-Jun NH₂-terminal kinase; MAFbx, or Atrogin-1; MuRF-1, muscle RING-finger protein-1; mTOR, mammalian target of rapamycin; mTORC1, mTOR complex 1; NAD, nicotinamide adenine dinucleotide; PA, phosphatidic acid; p70S6K, ribosomal protein S6K; PDH, prolyl hydroxylase; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; PI13K, phosphatidylinositol 3-kinase; Rheb, Ras homolog enriched in brain gene; ROS, reactive oxygen species; SIRT, sirtuin; Tsc1, tuberous sclerosis complex 1; Tsc2, tuberous sclerosis complex 2. Color images available online at www.liebertpub.com/rej

FIG. 3.

Main signaling pathways involved in the exercise effects in neurodegeneration, especially with regard to Alzheimer's disease. 4-HNE, 4-hydroxynonenal; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; Aβ, amyloid-pβ; BACE, β-secretase; BDNF, brain-derived-neurotrophic factor; IGF-1, insulin-like growth factor 1; LTP, long-term potentiation; MDA, malondialdehyde; RCD, reactive carbonyl derivative; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor. Color images available online at www.liebertpub.com/rej