Program Director/Principal Investigator (Last, First, Middle): Project Summary Reduced skeletal muscle mitochondrial oxidative capacity of skeletal muscle has been implicated in aging- related declines in cardiorespiratory fitness, physical functioning, and cardiometabolic health. Although exercise training in older adults increases mitochondrial capacity, virtually all of the data is reported in terms of average responses within groups. Yet within groups, there is enormous inter-individual variation in these responses. Two specific questions remain regarding the significance and implications of exercise-induced changes in mitochondrial capacity. 1) Does exercise improve mitochondrial capacity similarly in older and younger adults? 2) What are the molecular signatures within skeletal muscle that associate with improvements in mitochondrial capacity in older and younger adults? We will address these major gaps in knowledge by objectively assessing the spectrum of mitochondrial capacity responses to exercise in vivo, investigating the underlying molecular regulation of exercise responses, and relating the mitochondrial responses and molecular factors to clinically-relevant outcomes such as exercise-induced improvements in cardiorespiratory fitness (VO2max). The NIH-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC) funds collection of comprehensive molecular signatures from biospecimens before and after 12 weeks of aerobic and resistance exercise training in healthy adults spanning the adult age span. This ancillary study will synergize with MoTrPAC and will add measurements of mitochondrial capacity of the skeletal muscle via non-invasive 31P magnetic resonance spectroscopy (31P-MRS) before and after training in 420 individuals across a wide age range (18 to 60+). Aim 1 is to assess differences in the mitochondrial capacity response to exercise training across the agespan and between aerobic and resistance training. Aim 2 is to identify molecular transducers of mitochondrial capacity induced by exercise. Primary hypotheses are that a proportion of individuals will not improve mitochondrial capacity following exercise training regardless of modality; age per se will not correlate with mitochondrial capacity responses; that greater improvements in mitochondrial capacity will associate similarly with greater improvements in cardiorespiratory fitness in younger and older adults; and that mitochondrial capacity responses will be greater with aerobic training compared to resistance training but aerobic-resistance differences will be similar across age groups. The impact of the project is that it will leverage the high-throughput `omics' technologies and exercise studies provided by MoTrPAC to shed light on mechanisms underlying the variation in mitochondrial capacity responses linked to health benefits of physical activity in older adults. OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page