In this report we will provide additional insight on the individual features of age-related causes of mobility limitation, explaining why insulin resistance, related to lower muscle functioning, sub-inflammation and hormonal changes, may contribute to its onset and sustain it. According to the recent literature, the same factors playing a role in the onset and maintenance of insulin resistance are related to mobility limitation. Thus, the presence of insulin resistance can be considered a biomarker of susceptibility to mobility limitation among older persons. All described factors related to both conditions are strictly intertwined. Therefore, the identification and correction of a single factor is difficult to convert into clinical practice. Instead, insulin resistance may be considered not only an early biological marker, but also a predictive and modifiable marker of mobility limitation. Thus, interventions aimed at correcting insulin resistance may have a potential role in preventing or at least slowing down functional decline in the elderly population, promoting a better quality of life and potentially extending the “healthspan”.