Proteostasis describes the control of, and balance between tissues rates of protein synthesis and breakdown. The two main external factors governing skeletal muscle proteostasis are nutrition and loading patterns, as can be illustrated by the muscle catabolism that occurs with starvation and unloading (atrophy), or in contrast, the anabolic effects of loading (hypertrophy). The principal means by which nutrition and loading regulate proteostasis is through controlling both arms of protein turnover i.e. protein synthesis (PS) and protein breakdown (PB). For instance, in periods of inactivity and nutritional deficiency- such as when sleeping- there exists a disequilibrium (PB>PS) which is reversible only upon restoration of activity and nutritional supply in the waking hours (PS>PB). It follows that maintenance of this dynamic equilibrium (and thus muscle mass) requires ‘regular’ physical activity and nutrition. Of all nutrients, it is solely the essential amino acids (EAA) (1) which cause the large (~3-fold) albeit brief (~1.5 h saturable at ~10 g EAA (2, 3)) rise in MPS after feeding. The related increase in insulin orchestrates a more minor role, suppressing PB ~50% but having no functional role in EAA-induced increases in MPS (4). Loading of muscle (i.e. exercise) stimulates MPS to a similar amplitude to that of EAA supply, with the difference being that raised MPS persists for longer durations (4-24 h) depending upon the strength of the exercise stimulus and nutrient status (5). Intracellular signalling pathways governing increases in PS with nutrition and exercise are complex and in the latter case involve integration of extracellular cues (e.g. growth factors), ions (e.g. Ca2+), mechano-transduction and synergy with nutrient signalling. Nonetheless, to a large extent, nutrient and exercise-induced signalling converge on the mammalian-target of rapamycin (mTOR). It has been long known that ageing is associated with declines in muscle mass and function; termed sarcopenia and dynapenia, respectively. Age-related loss of muscle mass and strength are incipient processes leading to frailty, increased risk of metabolic disease, loss of mobility and increased mortality; often precipitated principally by falls (an estimated 25% to 39% of adults >65 y fall each year with a 20% <2 y mortality rate). However, until recently there had been no explanation available in terms of the underlying dysregulation of proteostasis underpinning sarcopenia since there exists no depressions in PS, or increases in PB, at least where comparisons have been between younger and older humans under postabsorptive, rested conditions (3). On this basis it is of great interest that the concept of “anabolic resistance” has been an emerging feature of metabolic dysregulation in ageing muscles (3, 6-8). In a nutshell, anabolic resistance manifests as an acute blunting in PS and PB responses to the anabolic cues of physical activity and nutrition. This points toward an age-related nutrient and exercise resistance in protein metabolism (e.g. analogous to insulin resistance in glucose metabolism in type II Diabetes) and likely represents a key facet in the failure of ageing muscle to sustain a dynamic equilibrium in proteostasis such that over-time, sarcopenia develops. Consolidating the role of anabolic resistance as a causative and pervasive feature of muscle atrophy are reports of: (i) age-related blunting of hypertrophy after exercise-training (9), (ii) pre-clinical models reporting its existence and identifying an underlying mechanism as inflammation on the premise that cyclooxygenase inhibitors ameliorate sarcopenia commensurate with the reversal of anabolic resistance (10), and (iii) its extension beyond ageing into other conditions of muscle atrophy (e.g. immobilisation, type II Diabetes, Cancer cachexia, chronic heart failure (11-13). Nevertheless, work is needed to define the mechanistic basis of anabolic resistance in humans, the contribution of physical inactivity, and to find effective interventions with which to “overcome” it.