© 2016 Elsevier Inc. The impact of calorie amount on aging has been extensively described; however, variation over time and among laboratories in animal diet, housing condition, and strains complicates discerning the true influence of calories (energy) versus nutrients on lifespan. Within the dietary restriction field, single macronutrient manipulations have historically been researched as a means to reduce calories while maintaining adequate levels of essential nutrients. Recent reports of nutritional geometry, including rodent models, highlight the impact macronutrients have on whole organismal aging outcomes. However, other environmental factors (e.g., ambient temperature) may alter nutrient preferences and requirements revealing context specific outcomes. Herein we highlight factors that influence the energetic and nutrient demands of organisms which oftentimes have underappreciated impacts on clarifying interventional effects on health and longevity in aging studies and subsequent translation to improve the human condition.