Deletion of ghrelin prevents aging‐associated obesity and muscle dysfunction without affecting longevity

Abstract

SummaryDuring aging, decreases in energy expenditure and locomotor activity lead to body weight and fat gain. Aging is also associated with decreases in muscle strength and endurance leading to functional decline. Here, we show that lifelong deletion of ghrelin prevents development of obesity associated with aging by modulating food intake and energy expenditure. Ghrelin deletion also attenuated the decrease in phosphorylated adenosine monophosphate‐activated protein kinase (pAMPK) and downstream mediators in muscle, and increased the number of type IIa (fatigue resistant, oxidative) muscle fibers, preventing the decline in muscle strength and endurance seen with aging. Longevity was not affected by ghrelin deletion. Treatment of old mice with pharmacologic doses of ghrelin increased food intake, body weight, and muscle strength in both ghrelin wild‐type and knockout mice. These findings highlight the relevance of ghrelin during aging and identify a novel AMPK‐dependent mechanism for ghrelin action in muscle.

Ghrelin mediates exercise endurance and the feeding response post-exercise

“…The reduced exercise endurance that we observe here in GHSR-nulls contrasts with an increase in exercise endurance reported in a recent study using ghrelin-knockout mice [95] . Notable differences that might help explain these divergent results include age of mice (6–9 months-of-age and 21–24 months-of age as compared to the 2.5–4 month-old mice studied here) and intensity of exercise protocol (a high intensity endurance protocol incorporating relatively rapid increases in the treadmill speed as well as a 10° incline, leading to exhaustion before 20 min as compared to the less intense progressive endurance protocol without an incline used here, in which exhaustion was not reached until after 90 min and was associated with depletion of glycogen stores).…”

Efficacy of Exercise Time Models in Weight-Loss and Coronary Risk Panel of Middle-Aged Females

“…Weight loss parameters, consisting of body weight and coronary risk panel, changed at the post-test in comparison with the pre-test in both groups, indicating the efficacy of the interventions. Age advancement is associated with overweight and obesity (3,4), and these conditions are an independent risk factor for the development and progression of CHD (19,(22)(23)(24) because of hyperlipidemia (25,26). Earlier research shows that the coronary risk panel can be heavily influenced by weight loss (6,19,23).…”

“…Higher morbidity/mortality and higher social insurance costs are some effects of obesity among elderly grown-ups (1,2). Aging is associated with obesity (3). Around 70% of the populations of middle age or older (≥ 45 years of age) have an abnormal weight pick-up and these people are at a raised peril for obesity (4).…”

MicroRNA‐188 regulates aging‐associated metabolic phenotype

“…Aging is often accompanied by an irreversible decline in physiological function, especially metabolic function. The age‐associated metabolic phenotype, including decreased energy expenditure, increased fat mass accumulation, and insulin sensitivity deterioration (Guillory et al, ), can ultimately lead to age‐associated metabolic dysfunction, which correlates closely with several disease, such as type 2 diabetes (Lin et al, ), fatty liver (Gong, Tas, Yakar, & Muzumdar, ; Sheedfar et al, ), cardiovascular diseases (Dou et al, ), neurodegenerative diseases (Martocchia et al, ), and cancer (Topuz et al, ). Thus, exploring the underlying mechanisms of the age‐associated metabolic phenotype and developing drugs to treat aging‐associated metabolic dysfunction are of paramount importance.…”