Diet and exercise in frailty and sarcopenia. Molecular aspects
Open accessAbstract
Function declines throughout life although phenotypical manifestations in terms of frailty or disability are only seen in the later periods of our life. The causes underlying lifelong function decline are the aging process "per se", chronic diseases, and lifestyle factors. These three etiological causes result in the deterioration of several organs and systems which act synergistically to finally produce frailty and disability. Regardless of the causes, the skeletal muscle is the main organ affected by developing sarcopenia. In the first section of the manuscript, as an introduction, we review the quantitative and qualitative age-associated skeletal muscle changes leading to frailty and sarcopenia and their impact in the quality of life and independence in the elderly. The reversibility of frailty and sarcopenia are discussed in the second and third sections of the manuscript. The most effective intervention to delay and even reverse frailty is exercise training. We review the role of different training programs (resistance exercise, cardiorespiratory exercise, multicomponent exercise, and real-life interventions) not only as a preventive but also as a therapeutical strategy to promote healthy aging. We also devote a section in the text to the sexual dimorphic effects of exercise training interventions in aging. How to optimize the skeletal muscle anabolic response to exercise training with nutrition is also discussed in our manuscript. The concept of anabolic resistance and the evidence of the role of high-quality protein, essential amino acids, creatine, vitamin D, β-hydroxy-β-methylbutyrate, and Omega-3 fatty acids, is reviewed. In the last section of the manuscript, the main genetic interventions to promote robustness in preclinical models are discussed. We aim to highlight the molecular pathways that are involved in frailty and sarcopenia. The possibility to effectively target these signaling pathways in clinical practice to delay muscle aging is also discussed.
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Mitochondrial dysfunction leads to decreased energy production in muscle cells, impairing their ability to maintain mass and function.
“Mitochondrial dysfunction leads to decreased energy production in muscle cells, impairing their ability to maintain mass and function [7,8].”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [8]
Sarcopenic obesity in older women arises from molecular mechanisms including mitochondrial dysfunction, oxidative stress, and inflammatory pathways that contribute to muscle atrophy and fat accumulation.
“Sarcopenic obesity in older women arises from a complex interplay of molecular mechanisms that affect both adipose and muscle tissues. As detailed by Millán-Domingo et al. [8], these mechanisms include mitochondrial dysfunction, oxidative stress, and inflammatory pathways that contribute to muscle atrophy and fat accumulation.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [8]
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- Authors
- Millan-Domingo, F., Garcia-Dominguez, E., Gambini, J., Olaso-Gonzalez, G., Viña, J., & Gomez-Cabrera, M. C.
- Affiliations
- Universitat de València (ES)
- Venue
- Molecular Aspects of Medicine
- Publisher
- Elsevier BV
- Published
- 2024-12
- Volume
- 100
- Pages
- 101322
- ISSN
- 0098-2997 (ISSN-L)
- OpenAlex
- W4404699999
- Cited by
- 31
- References
- 41
- Citations by year
- 2026: 20 · 2025: 11
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Aspects of Medicine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Instituto de Salud Carlos III (CB16/10/00435)
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (MICIU/AEI/10.13039/501100011033)
- Horizon 2020 Framework Programme (825546)
- State Agency of Research (RED2022-134800-T)
- Government of Valencia Ministry of Innovation Universities Science and Society
- European Regional Development Fund (CIPROM/2022/56)
- Generalitat Valenciana
- Spain Ministry of Science and Innovation (PID2022-142470OB-I00)
- Ministerio de Ciencia e Innovación
- European Commission
- Topics
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Keywords
- frailty, sarcopenia, skeletal muscle aging, exercise training, resistance training, cardiorespiratory exercise, multicomponent exercise, anabolic resistance, protein nutrition, essential amino acids, creatine, vitamin D, beta-hydroxy-beta-methylbutyrate, omega-3 fatty acids, sex differences in aging, healthy aging, molecular pathways, quality of life in old age
- MeSH terms
- Frailty, Aging, Animals, Diet, Humans, Exercise, Muscle, Skeletal, Sarcopenia
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