Obesity and type 2 diabetes account for a considerable proportion of the global burden of age-related metabolic diseases. In age-related metabolic diseases, tissue crosstalk and metabolic regulation have been primarily linked to endocrine processes. Skeletal muscle and adipose tissue are endocrine organs that release myokines and adipokines into the bloodstream, respectively. These cytokines regulate metabolic responses in a variety of tissues, including skeletal muscle and adipose tissue. However, the intricate mechanisms underlying adipose–muscle crosstalk in age-related metabolic diseases are not fully understood. Recent exciting evidence suggests that myokines act to control adipose tissue functions, including lipolysis, browning, and inflammation, whereas adipokines mediate the beneficial actions of adipose tissue in the muscle, such as glucose uptake and metabolism. In this review, we assess the mechanisms of adipose-muscle crosstalk in age-related disorders and propose that the adipokines adiponectin and spexin, as well as the myokines irisin and interleukin-6 (IL-6), are crucial for maintaining the body's metabolic balance in age-related metabolic disorders. In addition, these changes of adipose-muscle crosstalk in response to exercise or dietary flavonoid consumption are part of the mechanisms of both functions in the remission of age-related metabolic disorders. A better understanding of the intricate relationships between adipose tissue and skeletal muscle could lead to more potent therapeutic approaches to prolong life and prevent age-related metabolic diseases. • The disorder of adipose–muscle crosstalk plays a critical role in the development of age-associated metabolic diseases. • Ageing-related endocrine changes in muscle and adipose tissue result in dysregulation of myokines and adipokines. • Adipokines (adiponectin and spexin) elevate muscle glucose uptake and insulin sensitivity. • Myokines (irisin and IL-6) act to control adipose tissue functions, including lipolysis, browning and inflammation. • Exercise or dietary flavonoid intake could regulate adipose-muscle crosstalk in age-related metabolic diseases. [ABSTRACT FROM AUTHOR]