Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise
Abstract
1. Introduction
2. Literature Search Strategy
3. Natural Compounds
Natural Compound | Chemical Class | Molecular Target | Study Population | Evidence | Reference |
---|---|---|---|---|---|
Resveratrol | Polyphenolic phytoalexin | SIRT1/AMPK | MSCs isolated from 12-month-old Kunming mice treated with resveratrol for 48 h | - Reduced ROS - Improved cell viability - Promoted extracellular matrix calcification - Increased expression of ALP, OCN, OPN, Col-I, RUNX2 | [36] |
SIRT1/FoxO1 | - 8-week-old ovariectomized female mice treated with resveratrol intraperitoneally (40 mg/kg body weight) once daily for 8 weeks - Murine osteoblasts subjected to H2O2-induced oxidative stress, treated with 0.1 mM resveratrol for 1, 3, and 5 days | In vivo: - Improved bone microarchitecture - Increased expression of ALP, RUNX2, Osx In vitro: - Promoted cell proliferation - Increased ALP activity - Increased SOD expression - Reduced ROS | [12] | ||
SIRT1 | 25-month-old Sprague-Dawley rats treated with oral resveratrol (150 mg/kg/day) for 6 weeks | - Increased AMPK, SIRT1, and Bcl-2 - Reduced Bax and p53 | [37] | ||
Rapamycin | Macrocyclic lactone | mTOR | 30-month-old female HET3 mice treated with rapamycin intraperitoneally (6 mg/kg body weight) every other day for 8 weeks | - mTORC1 inhibition - Reduced GDF15 and STAT3 expression - Attenuation of oxidative stress - Reduced muscle atrophy | [42] |
15 wild-type female mice aged 8 weeks treated with 4 mg/kg rapamycin intraperitoneally every other day for 12 weeks | - Reduced femoral bone mineral content - Reduced BMD - Increased serum CTX-1 - Increased bone resorption | [43] | |||
- Chondrocytes isolated from osteoarthritic patients treated with 1 µM RPMs for 48 h - Wild-type C57BL/6 male mice with post-traumatic osteoarthritis treated with 1.8 µg RPMs by intramuscular injection on days 7, 24 and 42 in the prophylactic study, and on days 24 and 42 in the therapeutic study | In vitro: - Autophagy induction - Reduced cellular senescence - Maintenance of sulphated glycosaminoglycan production In vivo: - Reduction in cartilage damage and inflammation in both preventive and therapeutic phases | [44] | |||
Quercetin | Flavonoid | NF-κB/β-catenin | - 8–10-week-old ovariectomized female Sprague Dawley rats treated with 50 mg/kg quercetin per day for 8 weeks - BMSCs treated with 1 µM quercetin for 24 h after stimulation with 5 ng/mL TNF-α | In vivo: - Improved trabecular microarchitecture and bone biomechanical properties In vitro: - Increased cell viability - Promoted bone mineralization - Increased RUNX2, Osx and β-catenin expression | [50] |
ERK/p38 | BMSCs isolated from 4-week-old male rats treated with quercetin at concentrations of 0, 1, 2, 5, and 10 μM for 7 days | Optimal results at 2 μM concentration: - Increased cell proliferation - Increased ALP activity - Promoted calcium deposition and osteogenesis - Increased VEGF and ANG-1 expression | [51] | ||
ITGB1/FAK/paxillin, IGF-1R/Akt/mTOR | C2C12 mouse myoblasts treated with quercetin at concentrations of 0, 2.5, 12.5, 25 and 50 µM for 7 days every 48 h | Optimal results at 12.5 µM concentration: - Increased cell fusion and migration - Increased myogenic differentiation - Promoted muscle regeneration | [53] | ||
Curcumin | Polyphenol | NRF2 | 18 male F344xBN rats aged 32 months fed with 0.2% curcumin for 4 months | - Increased muscle mass and contractile function - Increased NRF2 expression - Reduced oxidative damage | [10] |
Vitamin E | Tocopherols/Tocotrienols | NF-kB/STAT3 | Human myoblasts treated with 10 µM TRF, 10 µM ATF, or 5 µM NAC for 24 h | - Improved cell morphology and reduced senescence after NAC treatment - Reduced ROS production and lipid peroxidation after RTF and ATF treatments - Increased SOD activity and GSH/GSSG ratio after TRF treatment | [58] |
Genistein | Isoflavone | ERRα | BMSCs isolated from 12-week-old ovariectomized female Sprague-Dawley rats treated with genistein at doses of 1 μM and 10−2 μM for 3 days | - Reduced p53, p16 and p21 expression - Improved mitochondrial function - Reduced oxidative damage - Increased SIRT3 and PGC-1α expression - Reduced bone loss | [14] |
Fisetin | Flavonol | SIRT1 | - Primary human chondrocytes pretreated with fisetin at doses of 1, 5, 10 μM for 2 h, followed by stimulation with or without 10 ng/mL IL-1β for 24 h - 10-week-old male wild-type C57BL/6 mice treated with 20 mg/kg fisetin orally every day for 8 weeks | In vitro: - Reduced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, MMP-3, MMP-13 and ADAMTS-5 - Greater increase in SIRT1 expression at a concentration of 10 μM fisetin In vivo: - Attenuation of joint degeneration - Reduced subchondral bone plaque thickness - Reduced severity of synovitis | [60] |
Epicatechin | Flavonol | Akt/mTOR | 23-month-old male Sprague Dawley rats treated with 1 mg/kg/day oral epicatechin for 8 weeks | - Improved strength, endurance, and muscle mass - Increased IGF-1 and follistatin - Reduced TNF-α, myostatin - Inhibited NF-κB signaling, MuRF1 and Atrogin-1 | [61] |
4. Synthetic Compounds
Synthetic Compound | Molecular Target | Study Population | Evidence | Reference |
---|---|---|---|---|
Dasatinib | NF-κB | 12-month-old female ovariectomized rats treated orally with 5 mg/kg dasatinib and 50 mg/kg quercetin for 2 and 4 months | - Reduced bone loss - Reduced senescent cell accumulation - Restoration of MSCs functionality - Reduced NF-kB expression | [6] |
- Male C57BL/6 mice with facet joint osteoarthritis aged between 8 and 10 weeks treated orally with 5 mg/kg dasatinib and 50 mg/kg quercetin for 10 weeks - Primary mouse chondrocytes treated with 200 nM dasatinib and 10 μm quercetin for 48 h | In vivo: - Improvement in joint degeneration - Reduced expression of p16, p21, p53, IL-1β, IL-6 In vitro: - Attenuation of senescence and release of SASPs | [64] | ||
Navitoclax | Bcl-2/Bcl-xL | - 20 male (n = 10) and female (n = 10) 24-month-old C57BL/6 mice treated orally with 50 mg/kg navitoclax once daily for 2 weeks - Mouse BMSCs treated with 5 μM navitoclax for 5 days | In vivo: - Trabecular bone loss - Reduced mineralized matrix production - Reduced Osx expression In vitro: - Reduced cellular senescence - Compromised bone formation - Increased cytotoxicity | [7] |
UBX0101 | p53/p21 | 10-week-old or 19-month-old male C57BL/6 mice with induced osteoarthritis treated with 1 mM UBX0101 via six intra-articular injections every two days | Reduction in the presence of oxidized proteins in cartilage and synovial fluid in 19-month-old mice | [8] |
Panobinostat | FoxO | - Primary murine chondrocytes and synoviocytes treated with panobinostat at doses of 10, 50, and 100 nM for 24 h after stimulation with 5 ng/mL IL-1β - C57BL/6J mice treated with panobinostat at doses of 100 μg/kg and 2.5 mg/kg intraperitoneally 3 times a week for 11 weeks | In vitro: - Increased FoxO1, PRG4, ACAN expression - Reduced NOS2 expression In vivo: - Attenuated histopathological alterations in cartilage, synovium and subchondral bone - Improved pain-related behavioral parameters | [15] |
Metformin | AMPK/SIRT1 | - Mouse osteoblasts and MC3T3-E1 cell line treated with metformin at concentrations of 0–800 µM for 0–72 h - 45 female Sprague–Dawley rats aged 8–10 weeks, ovariectomized and treated with 100 mg/kg metformin orally every day for two months | In vitro: - Stimulated OPG and reduced RANKL mRNA and protein expression In vivo: - Increased BMD - Prevented bone loss - Increased OPG expression - Decreased RANKL expression | [67] |
- 15 male C57BL/6 mice aged 8 weeks treated with 16.5 mg/mL metformin intra-articularly every three days for 8 weeks - Chondrocytes isolated from 6 to 8-week-old male C57BL/6 mice treated with 1 mM metformin administered one hour before stimulation with 10 ng/mL IL-1β | In vivo: - Restored overexpression of MMP-13 and underexpression of Col-II in articular cartilage In vitro: - Increased phosphorylation of AMPK and SIRT1 - Promoted autophagy - Reduced catabolism and apoptosis | [68] | ||
C2C12 myoblasts at advanced passages treated with metformin at doses of 75 µM and 500 µM every 24 h for 2 days | Optimal results at 75 µM dose: - Reduced cellular senescence - Improved autophagy - Promoted myogenic differentiation | [16] |
5. Physical Exercise as a Non-Pharmacological Intervention Against Musculoskeletal Aging
Molecular Target | Study Population | Evidence | Reference |
---|---|---|---|
AMPK | - 9-week-old and 19-month-old male C57/BL6 mice subjected to moderate treadmill running (8 m/min) for 2 days, followed by 4 weeks of exercise training, 30 min twice a day with 1 h of rest, 5 days/week - Differentiated C2C12 myoblasts pretreated with 100 μM AICAR for 30 min prior to administration of 1 μM doxorubicin for 15 min | In vivo: - Reduced cellular senescence and p16 and p21 expression in 19-month-old male In vitro: - Pretreatment with AICAR attenuates doxorubicin-induced AMPK phosphorylation and prevents the cellular senescence phenotype | [24] |
AMPK/FOXO3a | 4-month-old male Sprague-Dawley rats: - Group D: treated with D-gal (200 mg/kg/day) - Group DS: D-gal + spermidine (5 mg/kg/day) - Group DE: D-gal + exercise (60 min of swimming per day, 5 days per week, for 6 weeks) - Group DES: D-gal + exercise + spermidine | Optimal results in the DES group: - Reduced SA-β-gal - Increased SOD activity - Reduced MDA levels - Promoted autophagy | [76] |
SIRT1/PGC-1α | 3-, 12- and 18-month-old female Sprague-Dawley rats subjected to swimming training for 40 min/day, 5 days/week for 12 weeks | - Upregulation of SIRT1, PGC-1α, and AMPK in the gastrocnemius and soleus muscles - Improved muscle function | [83] |
SIRT1 | Male Wistar rats aged 3 and 26 months subjected to treadmill running for 2 weeks at a speed of 10 m/min and a 5% incline for 30 min, progressively increased to 60% of VO2max | - Increased SIRT1 activity - Restored NAD+ and NAMPT levels - Increased UCP3 expression - Reduced HIF-1α and VEGF expression - Reduced oxidative stress and mitochondrial damage | [84] |
NOX4/SIRT1/FNDC5 | Wild-type BALB/c male mice aged 4, 12 and 24 months subjected to a WBV protocol consisting of 3 series of 2 min and 30 s each, with 2 min and 30 s of recovery, 3 days a week for 12 weeks | - Increase bone volume and trabecular thickness - Up-regulation of SIRT1 and FNDC5 - Down-regulation of NOX4 | [85] |
SIRT3 | 23 young subjects (aged 18–30, 11 women and 12 men) and 20 elderly subjects (aged ≥65, 9 women and 11 men) underwent 8 weeks of cycling at 65% of peak oxygen consumption for 60 min | - Reduction in oxidative damage in the skeletal muscle of young subjects - Increased SIRT3, CAT and SOD2 in the skeletal muscle of elderly subjects | [91] |
Akt/PGC-1α/FoxO3a | 7-week-old male Wistar rats subjected to treadmill running for 60 min a day, 4 times a week for 8 weeks | - Increase in the phosphorylation of Akt, FoxO3a and PGC-1α in the gastrocnemius and soleus muscles - Reduced MuRF1 and Atrogin-1 expression - Attenuation of muscle atrophy | [98] |
Akt/mTOR, Akt/FoxO3a | 21-month-old male Wistar rats subjected to resistance exercise, which consisted of climbing an inclined ladder with progressive loads applied to their tails until reaching 80% of their body weight | - Reduced Atrogin-1, MuRF1, p62 and Bax expression - Promoted autophagy - Increased expression of Beclin1, Bcl-2 and LC3-II/LC3-I ratio - Improved mitochondrial function - Increased PGC-1α, Mfn2, Drp1 and PINK1 expression | [99] |
NRF2 | 22-month-old wild-type C57/BL6/J male mice and 22-month-old NRF2 knockout mice subjected to 20 min of treadmill running per day for 8 weeks, with 1 day of rest per week Senescent C2C12 myoblasts treated with sulforaphane at different concentrations (0, 1, 2, 3, 4, 5 and 6 μM) for 20 h | In vivo (wild-type mice): - Improved muscle function - Reverted sarcopenic phenotype - Increased NRF2 expression In vitro: - Increased NRF2 and Drp1 expression - Promoted mitochondrial fission - Reduced cellular senescence | [100] |
6. Clinical Evidence on the Efficacy and Safety of Senotherapeutics and/or Combined with Physical Exercise
Compound | Study Type | Study Population | Evidence | Adverse Events | Reference |
---|---|---|---|---|---|
Resveratrol | Double-blind RCT | n = 30 older adults aged 65–80 years underwent to resistance training for 12 weeks: - Placebo group (n = 6 males, n = 9 females) - Treated group (n = 6 males, n = 9 females): 500 mg/day resveratrol for 12 weeks | In the treated group: - Improved mitochondrial density and muscle fatigue resistance - Increased fiber area and number of myonuclei in the vastus lateralis muscle | No adverse events reported during the study | [102] |
Three-arm, two-site pilot RCT | n = 60 older adults ≥ 65 years with physical limitations underwent to two sessions a week for 12 weeks of center-based walking and whole-body resistance training: - EX0 group (n = 6 males, n = 14 females): placebo for 12 weeks - EX500 group (n = 7 males, n = 13 females): 500 mg/day resveratrol for 12 weeks - EX1000 group (n = 2 males, n = 18 females): 1000 mg/day resveratrol for 12 weeks | In the EX1000 group: - Clinically significant improvement in the walking endurance - Increased citrate synthase | 27 adverse events (EX0, n = 8; EX500, n = 12; EX1000, n = 7) related to gastrointestinal or musculoskeletal problems | [103] | |
Double-blind crossover RCT | n = 128 postmenopausal women ≥ 65 years - Placebo group (n = 65) - Treated group (n = 63): 75 mg/day resveratrol for 12 months | In the treated group: - Increased BMD in the lumbar spine, femoral neck and total hip - Reduced plasma CTX-1 | Treated group: 4 subjects developed itching, menses, prolapsed bladder, prescheduled eye operation | [104] | |
Double-blind RCT | n = 92 knee osteoarthritic patients, average age 58 years - Placebo group (n = 10 males, n = 32 females): 15 mg meloxicam + placebo, once daily for 90 days - Treated group (n = 13 males, n = 37 females): 15 mg meloxicam + 500 mg resveratrol, once daily for 90 days | In the treated group: - Improvement in pain and physical function | No serious adverse events reported during the study | [106] | |
Rapamycin | Double-blind RCT | n = 114 healthy individuals aged 50–85 years: - Placebo group (n = 24 males, n = 15 females) - 5 mg/week of rapamycin (n = 23 males, n = 17 females) for 48 weeks - 10 mg/week of rapamycin (n = 27 males, n = 8 females) for 48 weeks | - Improvement in lean body mass and self-reported pain in the 10 mg/week rapamycin group - Improvement in self-reported emotional well-being and overall health in the 5 mg/week rapamycin group | Similar adverse events between groups, with a higher frequency of gastrointestinal symptoms in the treated groups | [108] |
Double-blind RCT | 25 healthy older adults aged 70–95 years Phase 1: - Placebo group (n = 4 males) - Treated group (n = 4 males): 1 mg/die rapamycin for 4 months Phase 2: - Placebo group (n = 5 males, n = 5 females) - Treated group (n = 5 males, n = 2 females): 1 mg/die rapamycin for 8 weeks | No significant differences in cognitive function, physical performance, or self-perceived health status between the experimental groups | - Phase 1: one subject treated with rapamycin developed nocturnal diarrhea after 11 weeks of treatment Phase 2 - Placebo group: one subject with self-limiting stomatitis - Treated group: three subjects developed, respectively, self-limiting stomatitis, diarrhea, and facial rash | [109] | |
Dasatinib Quercetin | Double-blind RCT | n = 60 postmenopausal women aged 60–90 years: - Control group (n = 30) - Treated group (n = 30): 100 mg/day dasatinib for two consecutive days + 1000 mg/day quercetin for three consecutive days orally with an intermittent schedule repeated every 28 days for 20 weeks | - Increased serum P1NP at 2 and 4 weeks in the treated group - No significant differences in serum CTX-1 between the two groups | Headaches and gastrointestinal events were more frequent in the treated group | [113] |
Quercetin | Double-blind RCT | n = 33 postmenopausal women aged 45–75 years: - Placebo group (n = 18) - Treated group (n = 15): 500 mg/day quercetin for 90 days | In the treated group: - Increased serum levels of osteocalcin, P1NP and CTX-1 - Reduced serum levels of IL-6 and TNF-α | No adverse events reported during the study | [114] |
Double-blind RCT | n = 26 older adults aged 65–82 years undergoing to isometric knee extension resistance training on both legs three times a week for 6 weeks: - Placebo group (n = 5 males, n = 8 females) - Treated group (n = 6 males, n = 7 females): 200 mg/day quercetin glycosides for 6 weeks | In the treated group: - Increased MVF of the knee extensor muscle - Increased motor unit firing rates with recruitment thresholds between 20 and 40% of MVF and between 40 and 60% of MVF | No adverse events reported during the study | [115] | |
Curcumin | Double-blind RCT | n = 30 healthy older adults ≥ 65 years (n = 13 males, n = 17 females) - Placebo group (n = 15) - Treated group (n = 15): 500 mg/day curcumin for 3 months | In the treated group: - Increased handgrip strength and weight lift strength | No serious adverse events reported during the study | [117] |
Triple-blind RCT | n = 120 postmenopausal women aged 50–65 years treated with 70 mg alendronate: - Placebo group (n = 30): placebo of nanomicelle curcumin + placebo of Nigella sativa oil once a day for 6 months - CUR group (n = 30): 80 mg nanomicelle curcumin + placebo of Nigella sativa oil once a day for 6 months - NS group (n = 30): placebo of nanomicelle curcumin + 1000 mg Nigella sativa oil once a day for 6 months - CUR-NS group (n = 30): 80 mg nanomicelle curcumin + 1000 mg Nigella sativa oil once a day for 6 months | - Reduced serum ALP in the CUR-NS group | No adverse events reported during the study | [118] | |
Vitamin E | Double-blind RCT | n = 52 postmenopausal osteopenic women aged over 45-year-old: - Placebo group (n = 26) - Treated group (n = 26): 400 IU/day mixed-tocopherol for 12 weeks | - Significant increase of 35.3% in CTX-1 at 12 weeks of supplementation compared to baseline in the placebo group - No significant change in CTX-1 and P1NP levels in the treated group | Postmenopausal bleeding after 10 weeks of supplementation in one participant, with spontaneous relief | [120] |
Double-blind RCT | n = 60 sarcopenic older adult subjects aged 60–85 years: - Placebo group (n = 14 males, n = 16 females) - Treated group (n = 13 males, n = 17 females): 57.5% whey protein, 702 IU vitamin D and 109 mg vitamin E for 6 months | In the treated group: - Improved RSMI and handgrip strength - Reduced serum levels of IL-2 - Improved quality of life | - Difficulty defecating in 3 subjects in the treated group - Pain during urination in one subject in the placebo group and one subject in the treated group | [121] | |
Genistein | Post hoc analysis using data from a multicenter RCT | n = 121 postmenopausal osteoporotic women, average age 54 years: - Placebo group (n = 59) - Treated group (n = 62): 54 mg/day genistein for 24 months | In the treated group: - Increased BMD in the femoral neck, lumbar spine, and total hip at 1 year and 2 years - Increased ALP level | Gastrointestinal problems were the most common adverse event after treatment | [126,127] |
Epicatechin | Double-blind RCT | n = 62 sarcopenic elderly males aged 65–75 years: - Placebo group (n = 15) - RT group (n = 14): 3 sets of 8–12 repetitions consisting of 45 min of leg press, leg extension, leg curl, chest press, shoulder press, rowing, biceps curl, and sit-ups, with a 90 s rest between sets, for 8 weeks - EP group (n = 17): 1 mg/kg/day epicatechin for 8 weeks - RT + EP group (n = 15) | In the RT, EP, and RT + EP groups: - Reduced time to complete the TUG test - Increased plasma follistatin levels - Increased follistatin/myostatin ratio, with higher values in the RT + EP group In the RT and RT + EP groups: - Increased maximum strength of chest press and leg press - Reduced plasma myostatin levels | No adverse events reported during the study | [132] |
Metformin | RCT | n = 132 older adult males ≥ 70 years - Placebo group (n = 70) - Treated group (n = 62): 1700 mg metformin twice a day for 16 weeks | In the treated group: - Increased handgrip strength, gait speed, and physical performance - Reduced plasma levels of CAF22 and NfL | Treated group: - Metallic taste (n = 5) - Soft stools/diarrhea (n = 9) - Flatulence (n = 7) | [134] |
7. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
SASP | Senescence-associated secretory phenotype |
mTOR | Mechanistic target of rapamycin |
NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
SIRT1 | Sirtuin 1 |
ERRα | Estrogen-related receptor alpha |
FoxO1 | Forkhead box O1 |
MSCs | Mesenchymal stem cells |
AICAR | 5-aminoimidazole-4-carboxamide ribonucleotide |
TNF-α | Tumor necrosis factor-alfa |
AMPK | AMP-activated protein kinase |
RUNX2 | Runt-related transcription factor 2 |
FoxO3 | Forkhead box O3 |
ROS | Reactive oxygen species |
ALP | Alkaline phosphatase |
OCN | Osteocalcin |
OPN | Osteopontin |
Col-I | Type I collagen |
Osx | Osterix |
SOD | Superoxide dismutase |
Bcl-2 | B-cell lymphoma 2 |
Bax | Bcl-2-associated X protein |
mTORC1 | mTOR complex 1 |
GDF15 | Growth differentiation factor 15 |
STAT3 | Signal transduced and activator of transcription 3 |
BMD | Bone mineral density |
CTX-1 | C-terminal telopeptide of type 1 collagen |
RPMs | Rapamycin-loaded poly(lactic-co-glycolic acid) microparticles |
BMSCs | Bone marrow stem cells |
VEGF | Vascular endothelial growth factor |
ANG-1 | Angiopoietin-1 |
ERK | Extracellular signal-regulated kinase |
ITGB1 | Integrin subunit beta 1 |
FAK | Focal adhesion kinase |
IGF-1R | Insulin-like growth factor 1 receptor |
NRF2 | Nuclear factor erythroid 2-related factor 2 |
IL-4 | Interleukin-4 |
IL-10 | Interleukin-10 |
CD206 | Cluster of differentiation 206 |
IL-1β | Interleukin-1 beta |
CCR7 | C-C motif chemokine receptor 7 |
iNOS | Inducible nitric oxide synthase |
ATF | α-tocopherol |
TRF | Tocotrienol-rich fraction |
NAC | N-acetylcysteine |
GSH/GSSG | Reduced/oxidized glutathione |
SIRT3 | Sirtuin 3 |
PGC-1α | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha |
IL-6 | Interleukin-6 |
TGF-β | Transforming growth factor beta |
NO | Nitric oxide |
PGE2 | Prostaglandin E2 |
COX-2 | Cyclooxygenase-2 |
MMP-3 | Matrix metalloproteinase-3 |
MMP-13 | Matrix metalloproteinase-13 |
ADAMTS-5 | A disintegrin and metalloproteinase with thrombospondin motifs 5 |
IGF-1 | Insulin-like growth factor 1 |
MuRF1 | Muscle ring-finger protein-1 |
SMAD | Suppressor of mothers against decapentaplegic homolog |
PI3K | Phosphoinositide 3-kinase |
Bcl-xL | B-cell lymphoma-extra large |
BMP-2 | Morphogenetic protein 2 |
PRG4 | Proteoglycan 4 |
ACAN | Aggrecan |
NOS2 | Nitric oxide synthase |
OPG | Osteoprotegerin |
RANKL | Receptor activator of nuclear factor kappa-B ligand |
NAD+/NADH | Nicotinamide adenine dinucleotide/reduced NAD+ |
SA-β-gal | Senescence-associated β-galactosidase |
MDA | Malondialdehyde |
NAMPT | Nicotinamide phosphoribosyltransferase |
UCP3 | Uncoupling protein 3 |
HIF-1α | Hypoxia-inducible factor 1-alpha |
WBV | Whole body vibration |
FNDC5 | Fibronectin type III domain-containing protein 5 |
NOX4 | NADPH oxidase 4 |
CAT | Catalase |
SOD2 | Superoxide dismutase 2 |
BAIBA | β-aminoisobutyric acid |
BDNF | Brain-derived neurotrophic factor |
EGF | Epidermal growth factor |
LC3 | Microtubule-associated protein 1A/1B-light chain 3 |
Mfn2 | Mitofusin 2 |
Drp1 | Dynamin-related protein 1 |
PINK1 | PTEN-induced kinase 1 |
RCT | Randomized controlled trial |
NSAIDs | Non-steroidal anti-inflammatory drugs |
P1NP | Procollagen type 1 N-terminal propeptide |
MVF | Maximal voluntary force |
RSMI | Relative skeletal mass index |
IL-2 | Interleukin-2 |
TUG | Timed up and go |
SPPB | Short physical performance battery |
CAF22 | C-terminal agrin-fragment-22 |
NfL | Neurofilament light chain |
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Falvino, A.; Bonanni, R.; Tarantino, U.; Tancredi, V.; Cariati, I. Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise. Int. J. Mol. Sci. 2025, 26, 7573. https://doi.org/10.3390/ijms26157573
Falvino A, Bonanni R, Tarantino U, Tancredi V, Cariati I. Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise. International Journal of Molecular Sciences. 2025; 26(15):7573. https://doi.org/10.3390/ijms26157573
Chicago/Turabian StyleFalvino, Angela, Roberto Bonanni, Umberto Tarantino, Virginia Tancredi, and Ida Cariati. 2025. "Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise" International Journal of Molecular Sciences 26, no. 15: 7573. https://doi.org/10.3390/ijms26157573
APA StyleFalvino, A., Bonanni, R., Tarantino, U., Tancredi, V., & Cariati, I. (2025). Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise. International Journal of Molecular Sciences, 26(15), 7573. https://doi.org/10.3390/ijms26157573