**1. Introduction**

Aging is often associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, frequently leading to a loss of independence and increased risk of mortality. The life expectancy of adults in many industrialized countries continues to increase [1], with persons aged ≥65 years representing the fastest growing segmen<sup>t</sup> of the US population [2]. While prolongation of life remains an important public health goal, of even greater significance is the extension of healthspan, often defined as continued intact functional capacity, and delay of the physiological changes that result in disease and disability [3,4]. For these reasons, there is a longstanding interest in understanding the biopsychosocial and functional determinants of successful aging [5]. Although many factors can contribute to functional decline, loss of muscle mass (sarcopenia) in particular, has been consistently linked to functional decline during aging [6].

Globally, sarcopenia has become a major health challenge, and is now recognized as a medical condition across the world [7,8]. In a recent multi-ethnic study (MEMOSA—Multi-Ethnic Molecular determinants of Sarcopenia) involving participants from Singapore, the UK, and Jamaica [9], the genome-wide transcriptomic profiles of skeletal muscle biopsies in 119 older men diagnosed with sarcopenia compared with age-matched controls were examined using high-coverage RNA sequencing. The novel and important finding of this study was that mitochondrial bioenergetic dysfunction was the strongest molecular signature of sarcopenia in men irrespective of ethnicity. Specifically, sarcopenia was associated with major impairments of oxidative phosphorylation, mitochondrial dynamics, and mitochondrial quality. Such findings strongly sugges<sup>t</sup> links between mitochondrial health, muscle quality, and physical function in older adults.

Exercise is widely known to improve mitochondrial health, potentially by providing a hormetic challenge that induces mitochondrial biogenesis [10]. Another potential intervention strategy for enhancing the metabolic flexibility of the mitochondria is intermittent fasting (IF), or more specifically, time-restricted feeding (TRF) [11]. This type of eating pattern involves a cessation in caloric intake commonly for 12–18 hours daily and has been shown to be su fficient to induce the metabolic switch from glucose to ketones as a source of energy for the mitochondria [12–14]. Specifically, this shift in metabolism takes place when nutrient availability is low and occurs at the point of negative energy balance when liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 h after cessation of caloric intake) [15,16].

In contrast to traditional caloric restriction paradigms, food is not consumed during designated fasting time periods but is typically not restricted during designated eating time periods. The length of the fasting time period can also vary but is frequently 12 or more continuous hours. There are many types of intermittent fasting approaches, but the two most popular and well-studied approaches are alternate day fasting (ADF) or alternate day modified fasting (ADMF) and TRF. Alternate day or alternate day modified fasting involves consuming no or very little food on fasting days and then alternating with a day of unrestricted food intake or a "feast" day. Time-restricted feeding interventions di ffer from ADF interventions in that individuals engage in daily fasts between 14 and 18 hours. Findings from a recent review indicate participants generally have high levels of adherence (range = 77% to 98%) with no serious adverse events to fasting regimens ranging in duration from two weeks to one year [17].

Several clinical trials now indicate that a TRF eating pattern can reduce fat mass with retention of lean mass in younger and middle-aged adults [18–21]; however, the e ffects of TRF are not well understood in adults aged 65 and older. We recently reported that a four-week TRF eating pattern was su fficient to induce weight loss and produce small but clinically meaningful improvements in physical function in overweight older adults [22]. Although these findings are promising, they are limited by the short duration of the intervention. Therefore, the present study aimed to better understand factors affecting adherence and feasibility of TRF in an older adult population.
