Fig. 1

Hypothetical hierarchical model of frailty. (1) This figure shows the central role of inflammation in multiple pathways leading to frailty. Aging, DNA damage, metabolic stress and chronic diseases lead to a systematic inflammatory response in the skeletal muscle, which induces the inflammatory signaling pathway. Additionally, other important pathways, such as the PI3K/Akt/mTOR, PGC-1α and oxidative stress pathways, are involved. Hormones and mitochondria also contribute pathogenically to frailty. Inflammation probably plays the most significant role in contributing to frailty. (2) There are four stages in the frailty process: skeletal muscle physiology (cell response pathways), preclinical progression of frailty, frailty initiation and irreversible damage. In the third stage, primary prevention may reverse the process. In the fourth stage, secondary prevention may delay the progression of frailty. Biomarkers can be found in the second, third and fourth stages. The identification of earlier biomarkers will allow better prognosis through prevention and intervention in elderly patients. Abbreviations: IL, interleukin; TNF, tissue necrosis factor; CRP, c-reactive protein; SASP, senescence-associated secretory phenotype; RNOS, Reactive nitrogen oxygen species; IGF-1, Insulin-like growth factor 1; PI3K, Phosphoinositide 3-kinase; Akt, Protein kinase B; mTOR, mammalian target of rapamycin; PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator − 1 α; 11βHSDα, 11β-Hydroxysteroid dehydrogenase α