Ulteriori strategie contro l’invecchiamento muscolare

Contrastare la perdita di forza, di massa muscolare e di funzionalità, rappresenta un’importante sfida per conservare la prestazione fisica e le condizioni generali di salute nel corso della vita. L’esercizio fisico, lo stile di vita e l’alimentazione hanno un ruolo decisivo per il mantenimento del patrimonio muscolare scheletrico e della sua efficienza.

Perdita di forza e massa muscolare

Intorno ai 50 anni d’età inizia una perdita di massa muscolare di circa l’8% per decade, fino a circa 70 anni. Successivamente, la perdita può aumentare fino al 15% per decade.

Il primo campanello d’allarme può essere la perdita di forza muscolare. Quando si riscontra anche una progressiva riduzione della massa muscolare, può trattarsi della condizione definita sarcopenia.

Nelle forme più gravi la sarcopenia causa la perdita delle prestazioni fisiche, ed ha un grave impatto sulla salute generale, con aumento del rischio di malattie croniche, ed incremento della mortalità.

La sarcopenia colpisce circa il 10-36% delle persone sopra i 60 anni d’età e circa il 30% degli over 80, con una prevalenza del 2-9% per le forme più gravi.

Sarcopenia: cause aggravanti

Oltre all’inarrestabile invecchiamento, tra le principali cause che possono aggravare il declino muscolare e l’insorgenza della sarcopenia, troviamo:

•   Malnutrizione, dovuta all’inadeguato apporto qualitativo e quantitativo  di carboidrati, proteine, grassi e micronutrienti (vitamine, minerali), ed all’insufficiente consumo di acqua / elettroliti (quantità raccomandate: donne 1,6 litri, uomini 2,0 litri /giorno).

•   Insufficiente attività fisica / sedentarietà, immobilità dovuta malattie ecc..

•   Sindrome metabolica, obesità, diabete, malattie renali e respiratorie croniche ecc..

•   Cambiamenti ormonali. Declino degli estrogeni nella donna, abbassamento del testosterone nell’uomo.  

La gestione della sarcopenia

La gestione della sarcopenia (1, 2) richiede un’approccio personalizzato, articolato sull’esercizio muscolare, l’appropriata alimentazione ed integrazione, es.: amino acidi essenziali, amino acidi ramificati come la leucina, creatina, acidi grassi omega 3, idrossi-metil-butirrato (HMB), proteine di alta qualità, probiotici, vitamine.

Nuove ricerche: ulteriori strategie per prevenire e attenuare la sarcopenia

Le crescenti conoscenze delle origini molecolari e cellulari del declino muscolare, delineano nuovi e promettenti sviluppi per ridurre i rischi della sarcopenia, con interventi sempre più mirati.

L’obiettivo consiste nell’ottimizzare: le attività delle cellule, la metabolizzazione dei nutrienti, la sintesi proteica e l’omeostasi muscolare, oltre a contribuire all’antiaging dell’intero organismo (1, 2, 3).

Questi effetti si possono raggiungere con l’uso di determinati antiossidanti / antinfiammatori, che riducono i fenomeni fisiopatologici alla base del declino muscolare (1, 2), oltre ad essere responsabili dell’invecchiamento generale dell’organismo (3, 4, 5, 6).

Infatti, anche per prevenire ed attenuare la sarcopenia, risulta vantaggioso combattere (1-10):

- infiammazione cronica / immunosenescenza (11-21);

- disfunzione mitocondriale / stress ossidativo (11, 58-67);

- senescenza cellulare ((1, 6, 11, 112-116);

- alterazioni del microbiota intestinale (1, 2, 6, 11, 126-133).

Inoltre, l’integrazione antiossidante / antinfiammatoria, ed un’adeguata alimentazione, permettono di aumentare le difese dell’organismo contro questi dannosi processi fisiopatologici (67-82).

Come  noto, queste difese fisiologiche subiscono un forte declino dovuto all’invecchiamento, che risulta più accentuato nelle persone affette da sarcopenia (10) e, ad esempio, in quelle sottoposte ad alcune terapie, come  le statine (70).

Un’ulteriore contributo deriva dal preservare l’integrità della barriera cutanea e la salute della pelle.

L’uso continuativo di specifici dermocosmetici contribuisce a ridurre significativamente l’infiammazione cronica e lo stress ossidativo a livello cutaneo e dell’intero organismo (54, 55, 56, 57).

L’integrazione alimentare per la salute muscolare

A marzo 2025 il British Medical Journal (BMJ) (83) ha pubblicato i risultati di una vasta indagine, oltre 19.000 soggetti, di cui l’8% affetti da sarcopenia, dove emergono i benefici dell’integrazione mirata per prevenirla e trattarla (83).

Antiossidanti, vitamine, oligoelementi (es.: magnesio, selenio, zinco) ecc. (2, 11, 83), forniscono un concreto supporto per la salute muscolare e per abbassare il rischio di complicazioni  (1, 2, 11, 83).

Ulteriori studi hanno messo in evidenza i benefici di varie sostanze, tra queste:

 - Polifenoli di origine vegetale, come: fisetina, curcumina, quercetina, resveratrolo (3, 22, 23).

Tra le molecole maggiormente studiate, il resveratrolo modula il sistema immunitario e le funzioni dei mitocondri, oltre a riequilibrare la composizione del microbiota intestinale, con positivi riflessi sul sistema osteomuscolare (1, 2, 3, 6, 11,  24-28, 98-104, 126-133).

Gli effetti simili agli estrogeni del resveratrolo contribuiscono a prevenire e attenuare in modo significativo la perdita di massa minerale ossea nel post-menopausa (27, 29).

- Vitamina C, D, E, complesso B contrastano i processi ossido-infiammatori, oltre a svolgere importanti attività immunomodulatrici e metaboliche (31, 32, 33, 34). Inoltre, contrastano la senescenza cellulare (1, 6, 112-116).

Queste vitamine sono indispensabili anche per il corretto funzionamento di vari meccanismi del microbiota intestinale (2, 134, 136, 137, 138).

Negli over 65 anni adeguati livelli sierici di vitamina B12 (35), dimostrano benefici anche sui seguenti parametri:

•   densità di massa ossea;

•   composizione corporea;

•   forza muscolare;

•   performance fisica.

Per questo, i livelli di B12 vengono considerati un valido indicatore della salute muscoloscheletrica (36-43).

La B12 regolarizza i livelli di omocisteina (36-43), un’azione svolta in sinergia con l’acido folico e la B6 (44, 45). Le alte concentrazioni ematiche di omocisteina alimentano i processi ossido-infiammatori, ed aumentano il rischio delle malattie cardiovascolari, neurologiche, metaboliche ecc. (44, 45). 

- Acidi grassi omega 3 oltre agli effetti antinfiammatori  (3, 40, 46, 47), dimostrano benefici per promuovere la sintesi proteica (48), attenuare la perdita di massa e migliorare la forza muscolare (1, 2, 48).

Inoltre, gli omega 3 contribuiscono a migliorare la performance fisica (2, 49, 50, 51, 52), ed a rallentare l’invecchiamento biologico (53).

- Coenzima Q10 è un potente antiossidante / antinfiammatorio, con un ruolo essenziale nella produzione di energia e per l’efficienza dei mitocondri (1, 11, 29, 30).

Adeguati livelli sierici di coenzima Q10 aiutano al mantenere e recuperare la salute muscolare (90, 91, 92), intervenendo a più livelli:

•   miglioramento delle funzioni vascolari e dello sfruttamento dell’ossigeno;

•   incremento della forza muscolare e della tolleranza allo sforzo;

•  accelerazione del recupero dopo l’esercizio fisico.

- Creatina ha una fondamentale funzione bioenergetica nei mitocondri. Inoltre, svolge importanti attività antiossidanti dirette ed indirette, significativi effetti sulla composizione corporea,  ed azioni immunoregolatrici e neuroregolatrici ecc. (11, 29). 

L’integrazione con creatina è ampiamente validata da molteplici studi, inclusi i significativi risultati conseguiti nei soggetti con declino muscolare, osteosarcopenia, deficit cognitivo e fragilità (93-97).

- N-acetilcisteina (NAC) permette di incrementare all’interno delle cellule la sintesi di glutatione, dotato di elevate capacità antiossidanti (10, 11, 90, 105),  oltre ad un diretto coinvolgimento nella funzionalità mitocondriale (106, 107).

La NAC contribuisce a migliorare l’insulino resistenza, le funzioni vascolari, la cognitività, la forza muscolare e la prestazione fisica, come  dimostrato alcuni studi clinici di lunga durata (90, 108, 109, 110).

A livello del microbiota intestinale ed in termini di prevenzione della sarcopenia, ricordiamo i benefici della dieta mediterranea (135), ed anche di alcune sostanze già citate:

glutatione, acidi grassi omega 3, coenzima Q10, creatina, oltre ai noti benefici di probiotici e prebiotici (2, 134, 136, 137, 138)

Antiossidanti ed ormoni sessuali

L’avanzamento dell’età, lo stile di vita, le malattie metaboliche ecc., influiscono sull’abbassamento delle concentrazioni degli ormoni sessuali femminili e maschili, creando condizioni predisponenti al declino muscolare ed osseo (65, 149-164).

Gli attuali orientamenti clinici non prevedono l’uso delle terapie ormonali (es.: testosterone) per la prevenzione ed il trattamento della sarcopenia, se non in casi accuratamente selezionati (11).

Mentre alcuni antiossidanti possono risultare utili per mitigare le problematiche di origine ormonali:

•   Nel peri- e post-menopausa, i fitoestrogeni, come  il resveratrolo, possono alleviare gli effetti del declino degli estrogeni, con positivi risultati contro l’osteoporosi, i disturbi metabolici e lo stress psicofisico (27, 65, 125, 171).

•   Nell’uomo l’integrazione di coenzima Q10 permette il significativo incremento dei livelli sierici di testosterone, come illustrato da una revisione della letteratura pubblicata a gennaio 2025 (172). 

•   Altre molecole bioattive, es.: vitamine C, D, E, B12, carnitina, polifenoli, NAC, acido folico, selenio, zinco,  possono contribuire a migliorare la sintesi cellulare di testosterone, il cui declino è minacciato anche in giovane età dai disturbi metabolici / sovrappesso, stile di vita, ecc. (1, 132, 133, 170).

INTEGRAZIONE ANTIAGING MIRATA E MULTIFUNZIONALE

Gli integratori studiati e commercializzati da Mitochon srl sono un prezioso supporto anche per preservare e recuperare la salute muscolare, oltre a rallentare l’invecchiamento biologico del nostro organismo.

•   L’integratore orosolubile Mitofast® con una associazione bilanciata (111) di ingredienti attivi: resveratrolo, coenzima Q10, N-acetilcisteina, N-acetilglucosamina, acido folico, vitamina C; incrementa le difese antiossidanti dell’organismo, riduce l’ossido-infiammazione ed i livelli di omocisteina, per combattere i disturbi dipendenti dall’età (175).

•  Mitofast B12  è integratore liquido di cianocobalamina per ottimizzare l’apporto di vitamina B12 (44, 45), che al bisogno può essere associato a Mitofast® per ottenere un’azione sinergica, finalizzata all’antiaging e per aumentare i livelli di energia, resistenza e benessere.

•   La linea cosmeceutica oltre ai significativi effetti antiaging, è un valido contributo per arginare l’infiammazione cronica dell’organismo, migliorando le difese della barriera cutanea (14, 30, 31, 45, 55-57). 

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54. Mini-review Pelle / Stress psicologico 2025 https://www.mitochon.it/linvecchiamento-della-pelle-causato-dallo-stress-psicologico/?v=0d149b90e739

55. Mini-Review AGEs - invecchiamento cutaneo 2025 https://www.mitochon.it/invecchiamento-cutaneo-e-prodotti-della-glicazione-avanzata-ages-4-possibili-strategie-per-combatterli/?v=0d149b90e739

56. Mini-Review Cellule cutanee - senescenza https://www.mitochon.it/le-ultime-scoperte-sullattivita-dei-mitocondri-cellule-cutanee-bersagli-e-risultati-dellantiaging-mitocondriale/

57. Mini-Review Precursori acido ascorbico https://www.mitochon.it/precursori-dellacido-ascorbico-per-massimizzare-lattivita-antiaging-per-via-topica-e-locale-ulteriori-acquisizioni-2024/

58. Kamarulzaman NT, Makpol S. The link between Mitochondria and Sarcopenia. J Physiol Biochem. 2025 Feb;81(1):1-20. doi: 10.1007/s13105-024-01062-7.

59. Liu D, Fan YB, Tao XH, Pan WL, Wu YX, Wang XH, He YQ, Xiao WF, Li YS. Mitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions. Aging Dis. 2021 Dec 1;12(8):2016-2030. doi: 10.14336/AD.2021.0427.

60. Marzetti E, Calvani R, Coelho-Junior HJ, Picca A. Mitochondrial pathways and sarcopenia in the geroscience era. J Nutr Health Aging. 2024 Dec;28(12):100397. doi: 10.1016/j.jnha.2024.100397. 

61. Affourtit C, Carré JE. Mitochondrial involvement in sarcopenia. Acta Physiol (Oxf). 2024 Mar;240(3):e14107. doi: 10.1111/apha.14107.

62. Blumer J, Le B. Rethinking sarcopenia and frailty of the elderly. Post Reprod Health. 2025 Apr 22:20533691251337173. doi: 10.1177/20533691251337173.

63. Wang, J.; Jia, D.; Zhang, Z.; Wang, D. Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis. Metabolites 2025, 15, 59. https://doi.org/10.3390/metabo15010059

64. Mini - Review Benessere e salute mitocodriale https://www.mitochon.it/obiettivo-benessere-partendo-dalla-salute-dei-mitocondri/

65. Tian X, Lou S and Shi R (2023) From mitochondria to sarcopenia: role of 17β-estradiol and testosterone. Front. Endocrinol. 14:1156583. doi: 10.3389/fendo.2023.1156583

66. Hongyang Xu, Jacob L. Brown, Shylesh Bhaskaran, Holly Van Remmen, Reactive oxygen species in the pathogenesis of sarcopenia, Free Radical Biology and Medicine, Vol. 227, 2025, Pages 446-458,

https://doi.org/10.1016/j.freeradbiomed.2024.11.046.

67. Bellanti, F.; Lo Buglio, A.; Quiete, S.; Dobrakowski, M.; Kasperczyk, A.; Kasperczyk, S.; Vendemiale, G. Sarcopenia Is Associated with Changes in Circulating Markers of Antioxidant/Oxidant Balance and Innate Immune Response. Antioxidants 2023, 12, 1992. https://doi.org/10.3390/antiox12111992

68. Yen CH, Chang PS, Chang YH, Lin PT. Identification of Coenzyme Q10 and Skeletal Muscle Protein Biomarkers as Potential Factors to Assist in the Diagnosis of Sarcopenia. Antioxidants (Basel). 2022 Apr 6;11(4):725. doi: 10.3390/antiox11040725.

69. Mini-Review Motivi per l’Integrazione Mirata https://www.mitochon.it/4-motivi-1-per-utilizzare-lintegrazione-mirata-contro-linvecchiamento-cutaneo-e-sistemico/

70. Mollazadeh H, Tavana E, Fanni G, Bo S, Banach M, Pirro M, von Haehling S, Jamialahmadi T, Sahebkar A. Effects of statins on mitochondrial pathways. J Cachexia Sarcopenia Muscle. 2021 Apr;12(2):237-251. doi: 10.1002/jcsm.12654. 

71. Ahmad K, Manongi NJ, Rajapandian R, Moti Wala S, Al Edani EM, Samuel EA, Arcia Franchini AP. Effectiveness of Coenzyme Q10 Supplementation in Statin-Induced Myopathy: A Systematic Review. Cureus. 2024 Aug 31;16(8):e68316. doi: 10.7759/cureus.68316.

72. Han X, Liu J, Gu Y, Li Y, Zhang W, Lv N, Dang A. Diabetes Risks of Statin Therapy-Coenzyme Q10 May Help. Rev Cardiovasc Med. 2025 Feb 19;26(2):26437. doi: 10.31083/RCM26437. 

73. Fogacci F, Giovannini M, Tocci G, Imbalzano E, Borghi C, Cicero AFG. Effect of Coenzyme Q10 on Physical Performance in Older Adults with Statin-Associated Asthenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Clin Med. 2024 Jun 26;13(13):3741. doi: 10.3390/jcm13133741. 

74. Yao Y, Yao J, Tang D, Wang H, Zhang H, Qiu J, Shu X. Dietary antioxidant capacity and sarcopenia: A study from US population. Nutrition. 2025 Feb;130:112613. doi: 10.1016/j.nut.2024.112613. 

75. Liu H, Xu Y, Li Q, Yang L, Yang X, Wang K, Gong Z, Zhang Q, Jia Y. Composite dietary antioxidant index of antioxidant vitamins and sarcopenia risk: insights from the UK biobank and NHANES cohorts. Nutr Metab (Lond). 2025 May 16;22(1):44. doi: 10.1186/s12986-025-00945-w. 

76. Lewis LN, Hayhoe RPG, Mulligan AA, Luben RN, Khaw KT, Welch AA. Lower Dietary and Circulating Vitamin C in Middle- and Older-Aged Men and Women Are Associated with Lower Estimated Skeletal Muscle Mass. J Nutr. 2020 Oct 12;150(10):2789-2798. doi: 10.1093/jn/nxaa221.

77. Liu L, Ding X, Zhang Y, Li T, Xu P, Ma Y, Xing H, Niu Q, Keerman M. Serum concentrations of different or multiple vitamins and Sarcopenia risk among US adults: insights from NHANES. BMC Public Health. 2024 Dec 4;24(1):3372. doi: 10.1186/s12889-024-20897-9.  

78. Zhang J, Fang W, Chen S, Wang L. Dietary total antioxidant capacity is closely associated with skeletal muscle mass: a cross-sectional study. Br J Nutr. 2024 Dec 28;132(12):1674-1683. doi: 10.1017/S0007114524002575. 

79. Aminianfar A, Hashemi R, Emami F, Heshmat R, Motlagh AD, Esmaillzadeh A. Associations between dietary total antioxidant capacity and sarcopenia: a cross-sectional study. Nutr J. 2024 Jul 31;23(1):87. doi: 10.1186/s12937-024-00933-5.

80. Yufan Wang, Li Liu, Shandi Yang, Bingquan Xiong, Xumin Xin. Association of Dietary Antioxidant Potential with Sarcopenia in Hypertension. Rev. Cardiovasc. Med. 2025, 26(4), 27138. https://doi.org/10.31083/RCM27138

81. Baharirad N, Pasdar Y, Nachvak M, Ghavamzadeh S, Soroush A, Saber A, Mostafai S, Naghipour A, Abdollahzad H. The relationship of dietary total antioxidant capacity with sarcopenia and cardiometabolic biomarkers in type 2 diabetes patients. Physiol Rep. 2022 Feb;10(3):e15190. doi: 10.14814/phy2.15190. 

82. van der Schaft N, Trajanoska K, Rivadeneira F, Ikram MA, Schoufour JD, Voortman T. Total Dietary Antioxidant Capacity and Longitudinal Trajectories of Body Composition. Antioxidants (Basel). 2020 Aug 10;9(8):728. doi: 10.3390/antiox9080728

83. Yun She, Lingling Zhu, Xiangyun Guo, Jinran Qin, Xiqiao Zhou, Jiangyi Yu, Qianhua Yan - Association between the composite dietary antioxidant index and sarcopenia risk in American adults: a cross-sectional NHANES study: BMJ Public Health 2025;3:e001447.

84. Hong WL, Huang H, Zeng X, Duan CY. Targeting mitochondrial quality control: new therapeutic strategies for major diseases. Mil Med Res. 2024 Aug 21;11(1):59. doi: 10.1186/s40779-024-00556-1.

85. Choi EH, Kim MH, Park SJ. Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment. Int J Mol Sci. 2024 Jul 21;25(14):7952. doi: 10.3390/ijms25147952.

86. Yang HM. Mitochondrial Dysfunction in Cardiovascular Diseases. Int J Mol Sci. 2025 Feb 23;26(5):1917. doi: 10.3390/ijms26051917.

87. Kathiresan DS, Balasubramani R, Marudhachalam K, Jaiswal P, Ramesh N, Sureshbabu SG, Puthamohan VM, Vijayan M. Role of Mitochondrial Dysfunctions in Neurodegenerative Disorders: Advances in Mitochondrial Biology. Mol Neurobiol. 2025 Jun;62(6):6827-6855. doi: 10.1007/s12035-024-04469-x.

88. Parmar UPS, Surico PL, Mori T, Singh RB, Cutrupi F, Premkishore P, Gallo Afflitto G, Di Zazzo A, Coassin M, Romano F. Antioxidants in Age-Related Macular Degeneration: Lights and Shadows. Antioxidants (Basel). 2025 Jan 27;14(2):152. doi: 10.3390/antiox14020152.

89. Pang M, Wang S, Shi T, Chen J. Overview of MitoQ on prevention and management of cardiometabolic diseases: a scoping review. Front Cardiovasc Med. 2025 Mar 11;12:1506460. doi: 10.3389/fcvm.2025.1506460.

90. Broome SC, Whitfield J, Karagounis LG, Hawley JA. Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing. Sports Med. 2024 Sep;54(9):2291-2309. doi: 10.1007/s40279-024-02072-7.

91. de la Bella-Garzón R, Fernández-Portero C, Alarcón D, Amián JG, López-Lluch G. Levels of Plasma Coenzyme Q10 Are Associated with Physical Capacity and Cardiovascular Risk in the Elderly. Antioxidants (Basel). 2022 Jan 29;11(2):279. doi: 10.3390/antiox11020279.

92. Bian Z, Wei L. The role of coenzyme Q10 in exercise tolerance and muscle strength. Arch Physiol Biochem. 2025 May 24:1-20. doi: 10.1080/13813455.2025.2507746.

93. Gutiérrez-Hellín J, Del Coso J, Franco-Andrés A, Gamonales JM, Espada MC, González-García J, López-Moreno M, Varillas-Delgado D. Creatine Supplementation Beyond Athletics: Benefits of Different Types of Creatine for Women, Vegans, and Clinical Populations-A Narrative Review. Nutrients. 2024 Dec 29;17(1):95. doi: 10.3390/nu17010095.

94. Candow DG, Moriarty T. Effects of Creatine Monohydrate Supplementation on Muscle, Bone and Brain- Hope or Hype for Older Adults? Curr Osteoporos Rep. 2024 Nov 1;23(1):1. doi: 10.1007/s11914-024-00895-x

95. Goes-Santos BR, Carson BP, da Fonseca GWP, von Haehling S. Nutritional strategies for improving sarcopenia outcomes in older adults: A narrative review. Pharmacol Res Perspect. 2024 Oct;12(5):e70019. doi: 10.1002/prp2.70019.

96. Candow DG, Kirk B, Chilibeck PD, Duque G. The potential of creatine monohydrate supplementation in the management of osteosarcopenia. Curr Opin Clin Nutr Metab Care. 2025 May 1;28(3):235-239. doi: 10.1097/MCO.0000000000001118. 

97. Kaufman MW, DeParis S, Oppezzo M, Mah C, Roche M, Frehlich L, Fredericson M. Nutritional Supplements for Healthy Aging: A Critical Analysis Review. Am J Lifestyle Med. 2024 Apr 9;19(3):346-360. doi: 10.1177/15598276241244725.

98. Russo, C.; Valle, M.S.; D’Angeli, F.; Surdo, S.; Malaguarnera, L. Resveratrol and Vitamin D: Eclectic Molecules Promoting Mitochondrial Health in Sarcopenia. Int. J. Mol. Sci. 2024, 25, 7503. https://doi.org/10.3390/ijms25147503

99. Pan C, Yang Y, Zhao Z, Hu J. Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction. Apoptosis. 2025 Apr;30(3-4):537-552. doi: 10.1007/s10495-024-02069-7.

100. Cano-Martínez A, Méndez-Castro JA, García-Vázquez VE, Carreón-Torres E, Díaz-Díaz E, Sánchez-Aguilar M, Castrejón-Téllez V, Rubio-Ruíz ME. A Combination of Resveratrol and Quercetin Prevents Sarcopenic Obesity: Its Role as a Signaling Inhibitor of Myostatin/ActRIIA and ActRIIB/Smad and as an Enhancer of Insulin Actions. Int J Mol Sci. 2025 May 21;26(10):4952. doi: 10.3390/ijms26104952.

101. Long Y, Wu Y, Zhong Y, Wu Y, Ye H, Luo Y, Xiao L, Ma Y, Wang M. Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments. Biomed Pharmacother. 2024 Oct;179:117396. doi: 10.1016/j.biopha.2024.117396.

102. Kondoh H, Kameda M. Metabolites in aging and aging-relevant diseases: Frailty, sarcopenia and cognitive decline. Geriatr Gerontol Int. 2024 Mar;24 Suppl 1(Suppl 1):44-48. doi: 10.1111/ggi.14684.

103. Shibata S, Kon S. Functional Ingredients Associated with the Prevention and Suppression of Locomotive Syndrome: A Review. Biol Pharm Bull. 2024;47(12):1978-1991. doi: 10.1248/bpb.b24-00443. 

104. Capozzi A, Saucier C, Bisbal C, Lambert K. Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises. Molecules. 2022 Oct 5;27(19):6594. doi: 10.3390/molecules27196594. 

105. Mini-Review Glutatione / NAC https://www.mitochon.it/glutatione-perche-proteggere-le-sue-concentrazioni-cellulari-nellantiaging/

106. Chen TH, Wang HC, Chang CJ, Lee SY. Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation. Int J Mol Sci. 2024 Jan 21;25(2):1314. doi: 10.3390/ijms25021314.

107. Liu Y, Liu S, Tomar A, Yen FS, Unlu G, Ropek N, Weber RA, Wang Y, Khan A, Gad M, Peng J, Terzi E, Alwaseem H, Pagano AE, Heissel S, Molina H, Allwein B, Kenny TC, Possemato RL, Zhao L, Hite RK, Vinogradova EV, Mansy SS, Birsoy K. Autoregulatory control of mitochondrial glutathione homeostasis. Science. 2023 Nov 17;382(6672):820-828. doi: 10.1126/science.adf4154.

108. Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, Sekhar RV. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clin Transl Med. 2021 Mar;11(3):e372. doi: 10.1002/ctm2.372.

109. Sekhar RV. GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging. J Nutr. 2021 Dec 3;151(12):3606-3616. doi: 10.1093/jn/nxab309.

110. Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):75-89. doi: 10.1093/gerona/glac135. 

111. Bellanti, F.; Coda, A.R.D.; Trecca, M.I.; Lo Buglio, A.; Serviddio, G.; Vendemiale, G. Redox Imbalance in Inflammation: The Interplay of Oxidative and Reductive Stress. Antioxidants 2025, 14, 656. https://doi.org/10.3390/antiox14060656

112. Falvino, A.; Gasperini, B.; Cariati, I.; Bonanni, R.; Chiavoghilefu, A.; Gasbarra, E.; Botta, A.; Tancredi, V.; Tarantino, U. Cellular Senescence: The Driving Force of Musculoskeletal Diseases. Biomedicines 2024, 12, 1948. https://doi.org/10.3390/biomedicines12091948

113. Sato R, Vatic M, Peixoto da Fonseca GW, Anker SD, von Haehling S. Biological basis and treatment of frailty and sarcopenia. Cardiovasc Res. 2024 Jul 31;120(9):982-998. doi: 10.1093/cvr/cvae073.

114. Kalykaki M, Rubio-Tomás T, Tavernarakis N. The role of mitochondria in cytokine and chemokine signalling during ageing. Mech Ageing Dev. 2024 Dec;222:111993. doi: 10.1016/j.mad.2024.111993. 

115. Lawton A, Tripodi N, Feehan J. Running on empty: Exploring stem cell exhaustion in geriatric musculoskeletal disease. Maturitas. 2024 Oct;188:108066. doi: 10.1016/j.maturitas.2024.108066. 

116. Xiong J, Guo Q, Luo X. Cellular senescence in age-related musculoskeletal diseases. Front Med. 2025 May 2. doi: 10.1007/s11684-025-1125-7. 

117. Ebrahimirad F, Mirmahdizade SE, Mahmoodieh B, Najafi S, Banihashemian SM, Nikakhtar S, Mobaraki H, Sadeghi A, Kossari N, SadatRafiei SK, Ghodsi Moghadam M, Mashkani A, Asadi Anar M and khosravi F (2025) Antioxidant strategies against cellular senescence: unveiling the power of synthetic versus natural antioxidants in a systematic review. Front. Aging 6:1543360. doi: 10.3389/fragi.2025.1543360

118. Santos TWD, Pereira QC, Fortunato IM, Oliveira FS, Alvarez MC, Ribeiro ML. Body Composition and Senescence: Impact of Polyphenols on Aging-Associated Events. Nutrients. 2024 Oct 25;16(21):3621. doi: 10.3390/nu16213621.

119. Varesi A, Chirumbolo S, Campagnoli LIM, Pierella E, Piccini GB, Carrara A, Ricevuti G, Scassellati C, Bonvicini C, Pascale A. The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence. Antioxidants (Basel). 2022 Jun 22;11(7):1224. doi: 10.3390/antiox11071224.

120. Emilio Sosa-Díaz, Estefani Yaquelin Hernández-Cruz, José Pedraza-Chaverri, The role of vitamin D on redox regulation and cellular senescence, Free Radical Biology and Medicine, Vol. 193, Part 1, 2022, Pages 253-273,

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121. Mariah F. Calubag, Paul D. Robbins, Dudley W. Lamming, A nutrigeroscience approach: Dietary macronutrients and cellular senescence, Cell Metabolism, Vol. 36, Issue 9, 2024, Pages 1914-1944, https://doi.org/10.1016/j.cmet.2024.07.025.

122. Guan L, Eisenmenger A, Crasta KC, Sandalova E, Maier AB. Therapeutic effect of dietary ingredients on cellular senescence in animals and humans: A systematic review. Ageing Res Rev. 2024 Mar;95:102238. doi: 10.1016/j.arr.2024.102238.

123. Simonenko SY, Bogdanova DA, Kuldyushev NA. Emerging Roles of Vitamin B12 in Aging and Inflammation. Int J Mol Sci. 2024 May 6;25(9):5044. doi: 10.3390/ijms25095044. 

124. Sah P, Rai AK, Syiem D. Sirtuin activators as an anti-aging intervention for longevity. Explor Drug Sci. 2025;3:100881. https://doi.org/10.37349/eds.2025.100881

125. Mini-Review Sovrappenso / Obesità - Resveratrolo - Antiossidanti 2025 https://www.mitochon.it/sovrappeso-obesita-quale-contributo-dal-resveratrolo-ed-altri-antiossidanti/?v=0d149b90e739

126. Jang DH, Shin JW, Shim E, Ohtani N, Jeon OH. The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review. Aging Cell. 2024 Oct;23(10):e14315. doi: 10.1111/acel.14315.

127. Jang DH, Shin JW, Shim E, Ohtani N, Jeon OH. The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review. Aging Cell. 2024 Oct;23(10):e14315. doi: 10.1111/acel.14315.

xx. Wang L, He X, Zhang Z, Chen N. Distinct gut microbiota signatures in older people with sarcopenic obesity and sarcopenia without obesity. Clin Nutr. 2025 Jun;49:77-89. doi: 10.1016/j.clnu.2025.04.004.

128. Wang G, Li Y, Liu H, Yu X. Gut microbiota in patients with sarcopenia: a systematic review and meta-analysis. Front Microbiol. 2025 Jan 22;16:1513253. doi: 10.3389/fmicb.2025.1513253.

129. José Neto N, Duarte Brito M, Gomes CDS, Corrêa LCAC, Guerra GCB, Guerra RO. Gut microbiota dysbiosis, sarcopenia, osteoporosis and osteosarcopenia in older people: A systematic review protocol. PLoS One. 2025 Jan 2;20(1):e0313193. doi: 10.1371/journal.pone.0313193.  

130. Hosseini FS, Behrouzi A, Shafaie E, Sharifi F, Ejtahed HS. Assessment of gut microbiota in the elderly with sarcopenic obesity: a case-control study. J Diabetes Metab Disord. 2025 Mar 15;24(1):83. doi: 10.1007/s40200-025-01584-x.

131. Barber, T.M.; Kabisch, S.; Pfeiffer, A.F.H.; Weickert, M.O. The Gut Microbiome as a Key Determinant of the Heritability of Body Mass Index. Nutrients 2025, 17, 1713. https://doi.org/10.3390/nu17101713

132. Mini-Review Sindrome Metabolica https://www.mitochon.it/sindrome-metabolica-2024-dalle-origini-molecolari-al-ruolo-dei-nutraceutici/

133. Mini-Review Steatosi Epatica https://www.mitochon.it/steatosi-epatica-novita-sui-meccanismi-dinsorgenza-ed-il-contributo-degli-antiossidanti/

134. Mini-Review Vitamine complesso B - microbiota https://www.mitochon.it/le-vitamine-del-gruppo-b-cosa-ce-di-nuovo-parte-2/

135. González-Rodríguez LG, Borrás Olivares I, Ghazi Y, Lozano Estevan MC, Ortega RM. Alimentación para mantener una adecuada salud muscular y ósea [Diet to maintain adequate muscle and bone health]. Nutr Hosp. 2024 Sep 23;41(Spec No3):12-15. Spanish. doi: 10.20960/nh.05449.

136. Das S, Preethi B, Kushwaha S, Shrivastava R. Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management. Histol Histopathol. 2024 Nov;39(11):1395-1425. doi: 10.14670/HH-18-730. 

137. Chang SS, Chen LH, Huang KC, Huang SW, Chang CC, Liao KW, Hu EC, Chen YP, Chen YW, Hsu PC, Huang HY. Plant-based polyphenol rich protein supplementation attenuated skeletal muscle loss and lowered the LDL level via gut microbiota remodeling in Taiwan's community-dwelling elderly. Food Funct. 2023 Oct 16;14(20):9407-9418. doi: 10.1039/d3fo02766j.

138. Sim M, Hong S, Jung MH, Choi EY, Hwang GS, Shin DM, Kim CS. Gut microbiota links vitamin C supplementation to enhanced mental vitality in healthy young adults with suboptimal vitamin C status: A randomized, double-blind, placebo-controlled trial. Brain Behav Immun. 2025 Apr 3;128:179-191. doi: 10.1016/j.bbi.2025.03.032. 

139. Kuczmarski, M.F.; Orsega-Smith, E.; Beydoun, M.A.; Evans, M.K.; Zonderman, A.B. Protein Intake and Diet Quality Mediate the Relationship Between Sleep and Handgrip Strength in Adults in the HANDLS Study. Nutrients 2025, 17, 1900. https://doi.org/10.3390/nu17111900

140. Polo-Ferrero, L.; Martin, M.J.; Puente-González, A.S.; Barbero-Iglesias, F.J.; González-Manzano, S.; Méndez-Sánchez, R. Efficacy of Power Training on Sarcopenic Obesity in Community-Dwelling Older Women: A 32-Week Randomized Clinical Trial. Nutrients 2025, 17, 1822. https://doi.org/10.3390/nu17111822

141. Podraza-Farhanieh A, Spinelli R, Zatterale F, Nerstedt A, Gogg S, Blüher M, Smith U. Physical training reduces cell senescence and associated insulin resistance in skeletal muscle. Mol Metab. 2025 May;95:102130. doi: 10.1016/j.molmet.2025.102130. 

142. Nilsson, M.I.; Xhuti, D.; de Maat, N.M.; Hettinga, B.P.; Tarnopolsky, M.A. Obesity and Metabolic Disease Impair the Anabolic Response to Protein Supplementation and Resistance Exercise: A Retrospective Analysis of a Randomized Clinical Trial with Implications for Aging, Sarcopenic Obesity, and Weight Management. Nutrients 2024, 16, 4407. https://doi.org/10.3390/nu16244407

143. Paulussen KJM, McKenna CF, Beals JW, Wilund KR, Salvador AF and Burd NA (2021) Anabolic Resistance of Muscle Protein Turnover Comes in Various Shapes and Sizes. Front. Nutr. 8:615849. doi: 10.3389/fnut.2021.615849

144. Liu S, Zhang L, Li S. Advances in nutritional supplementation for sarcopenia management. Front Nutr. 2023 Jul 10;10:1189522. doi: 10.3389/fnut.2023.1189522. 

145. Hinssen F, Mensink M, Huppertz T, van der Wielen N. Impact of aging on the digestive system related to protein digestion in vivo. Crit Rev Food Sci Nutr. 2024 Nov 27:1-17. doi: 10.1080/10408398.2024.2433598. Epub ahead of print. PMID: 39601792.

146. Fujihira K, Takahashi M, Wang C, Fuke S, Hayashi N. Consumption of hot protein-containing drink accelerates gastric emptying rate and is associated with higher hunger levels in older adults. Temperature (Austin). 2023 Nov 19;11(1):52-59. doi: 10.1080/23328940.2023.2278410. 

147. Garvey SM, Madden EN, Qu Y, Best CH, Tinker KM. The Effects of a Microbial Enzyme Mixture on Macronutrient Hydrolysis in a Static Simulation of Oro-Gastric Digestion That Models Human Digestive Senescence. Foods. 2025 Mar 10;14(6):937. doi: 10.3390/foods14060937.

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