Ghrelin may be an effective treatment for age-related muscle loss

Sep 2020

The hormone, ghrelin, may help protect the elderly population from muscle loss, according to a study being presented at e-ECE 2020. The study found that administering a particular form of ghrelin to older mice helped to restore muscle mass and strength. As muscle-related diseases are a serious health concern in the elderly population, these findings suggest a potential new treatment strategy for muscle loss to enable the aging population to remain fit and healthy.

The hormone, ghrelin, may help protect the elderly population from muscle loss, according to a study being presented at e-ECE 2020. The study found that administering a particular form of ghrelin to older mice helped to restore muscle mass and strength. As muscle-related diseases are a serious health concern in the elderly population, these findings suggest a potential new treatment strategy for muscle loss to enable the aging population to remain fit and healthy.

Age-related skeletal muscle mass loss, in absence of any underlying disease, is defined as sarcopenia, which leads to deterioration of elderly people’s quality of life. It causes a decline in muscle mass and functionality, often resulting in poor balance, higher risk of falls or fractures, immobilisation and loss of independence.

Ghrelin is a hormone involved in metabolic regulation and energy balance through activation of appetite, but also plays an important role in protecting against muscle wasting. Both acylated (AG) and unacylated (UnAG) forms are present in the body, but UnAG does not bind to the AG receptor (GHSR-1a), so does not increase appetite. A growing body of evidence indicates that UnAG is acting at an unidentified receptor, which also mediates some common AG and UnAG biological activities, including a strikingly protective effect against muscle wasting. Ghrelin levels decline as we age and may be involved in the development of sarcopenia, but the role of AG versus UnAG in this process has not been investigated previously.

Dr Emanuela Agosti, and her team at the University of Piemonte Orientale in Italy, investigated how ghrelin affected age-related decline of muscle mass and function, by either deleting the ghrelin gene in mice, or overexpressing unAG. Muscle function as they aged was assessed through a wire hanging test, during which “falling” and “reaching” scores were recorded, to assess whole body strength and endurance. Both the deletion of the ghrelin gene and the lifelong overexpression of UnAG reduced age-associated decline in muscle mass and function. Despite both groups of animals displaying similar aging tendencies in body weight and muscle mass, the mice overexpressing UnAG maintained better muscle structure, performance and metabolism, more typical of muscle in younger mice.

“Understanding the causes and effects of sarcopenia will improve our ability to prevent, detect, and hopefully manage this disease. These findings provide novel understanding and point to UnAG, or analogues, as a possible therapeutic target for future treatment,” Dr Agosti comments.

The study indicates that UnAG, or possibly drugs that mimic it, can preserve muscle function and reduce the risk of age-related sarcopenia, without causing weight gain and obesity.

“Due to the worldwide increase in the elderly population, sarcopenia has an important social impact greatly affecting both aged people’s quality of life and government health care costs. Therefore, therapeutic strategies aimed at preventing and/or reducing sarcopenia are of pivotal importance.” Dr Agosti adds.

Dr Agosti and her colleagues now plan to identify the receptor mediating UnAG biological activities. This will help better define the molecular pathways involved in AG/UnAG actions and to design treatments that may reduce loss of muscle mass in sarcopenia and other similar conditions.



Both ghrelin deletion and unacylated ghrelin overexpression preserve muscles in aging mice
Emanuela Agosti, Marilisa De Feudis, Elia Angelino, Roberta Belli, Maraiza Alves Teixeira, Ivan Zaggia, Tommaso Raiteri, Andrea Scircoli, Andrea Graziani, Flavia Prodam, Maurilio Sanpaolesi, Paola Costelli, Elisabetta Ferraro, Simone Reano, Nicoletta Filigheddu

Sarcopenia, the decline in muscle mass and functionality during aging, might arise from age-associated endocrine dysfunction. Indeed, muscle wasting follows the general decline in trophic hormones and the establishment of a chronic mild inflammatory status characteristic of aging. Ghrelin is a gastric hormone peptide circulating in both acylated (AG) and unacylated (UnAG) forms that have anti-atrophic activity on skeletal muscle. AG is the endogenous ligand of the growth hormone secretagogue receptor (GHSR-1a), and it is involved in metabolic regulation and energetic balance through induction of appetite, food intake, and adiposity. UnAG does not induce GH release and has no direct effects on food intake, but it shares with AG several biological activities on cell types lacking AG receptor. In particular, both AG and UnAG have direct biological activities on skeletal muscle, including promotion of myoblast differentiation and protection from atrophy, in all likelihood by activating a common receptor. Also, UnAG promotes muscle regeneration, stimulation of muscle satellite cell activity, and activates autophagy and mitophagy at higher extent than AG in muscles of nephrectomyzed mice. Age-dependent hypoghrelinemia could participate in the establishment of sarcopenia by facilitating the progression of muscle atrophy and limiting skeletal muscle regeneration capability. Here, we show that both the deletion of the ghrelin gene (Ghrl KO) and the lifelong overexpression of UnAG (Tg) in mice attenuated the age-associated decline in muscle mass and functionality, seen as larger myofiber areas, lower levels of Atrogin-1, an increased mitochondrial functionality compared to old WT animals. Also, both Ghrl KO and Tg animals displayed reduced systemic inflammation and maintenance of brown adipose tissue functionality. While old Tg mice apparently preserved the characteristics of young animals, Ghrl KO mice features deteriorate with aging. However, young Ghrl KO mice show more favorable features compared to WT animals that result, on the whole, in better performances in aged Ghrl KO mice. Altogether, the data collected suggest that, in Ghrl KO mice, it is the lack of AG the major determinant factor of their overall better conditions and advocate for the design of analogs to UnAG rather than AG to therapeutically treat sarcopenia in humans.

Notes for Editors

The presentation, “Both ghrelin deletion and unacylated ghrelin overexpression preserve muscles in aging mice” was presented on Tuesday 8 September 2020 at 13:15 CET, online during e-ECE 2020.

e-ECE 2020 was held online on the 5-9 September. Catch up on ESE On-Demand.

The European Society of Endocrinology was created to promote research, education and clinical practice in endocrinology by the organisation of conferences, training courses and publications, by raising public awareness, liaison with national and international legislators, and by any other appropriate means.


Obesity is linked to heavy periods and impaired womb repair
COVID-19 infection may impair fertility in men
Vitamin D levels in the blood can predict future health risks & death
Skin lightening products linked to altered steroid hormone levels
Probiotics may help manage childhood obesity
Ghrelin may be an effective treatment for age-related muscle loss
Evaluating hormone-related targets & risks associated with COVID-19
Thyroid inflammation linked to anxiety disorders
COVID-19 severity is increased in patients with mild obesity
Larger thighs associated with lower risk of heart disease in obesity
Mindfulness helps obese children lose weight
Common anti-inflammatory may increase risk of diabetes
Vitamin B12 deficiency linked to obesity during pregnancy
Impaired liver function during pregnancy may increase risk of childhood obesity
Stress with disrupted body clock increases risk of metabolic disease
New insights into cause and treatments for aggressive form of breast cancer
Age is not a barrier to the benefits of weight-loss surgery
Limiting mealtimes may increase your motivation for exercise
Probiotic supplements may enhance weight loss in obese children
Smoking during pregnancy may damage daughters’ future fertility
Protective effect of breastfeeding on childhood obesity risk linked to leptin gene modification
Men ignore serious health risks of steroid abuse in pursuit of the body beautiful
Sleep problems in teenagers reversed in just one week by limiting screen use
Environmental toxins can impair sexual development and fertility of future generations
Setting fair regulations for top female athletes that have naturally higher testosterone levels
Breastfeeding reduces long-term risk of heart disease in mothers
Obesity risk may be increased by exposure to common environmental chemicals
Mentally tiring work may increase diabetes risk in women
Antioxidants may prevent cognitive impairment in diabetes
Skin inflammation may increase your risk of type-2 diabetes
Debate - Is the gut or the brain more important in regulating appetite and metabolism?
Routine vitamin B12 screening may prevent irreversible nerve damage in type-2 diabetes
Good nutrition could protect children from cognitive difficulties caused by early-life stress
Women more resilient to extreme physical activity than previously reported
Oestrogens in cows’ milk are unlikely to pose a threat to adult health
Diabetic patients are more at risk of death from alcohol, accidents and suicide
Too much vitamin A may increase risk of bone fractures
Vitamin D supplements may promote weight loss in obese children
Vitamin B supplements may protect kidney function in children with diabetes
Bad habits in childhood may lead to an ‘unhealthy’ balance of gut bacteria and increase health risks in later life
Lord Robert Winston cautions that advances in infertility therapies may be hindered by over-regulation
New link identified between inflammation and depression in type-1 diabetes
Walking a tightrope: universal thyroid testing could reduce pregnancy problems in some cases, but interfere with healthy pregnancies in others
Transgender brains are more like their desired gender from an early age
Larger waistlines are linked to higher risk of vitamin D deficiency
Brain stimulation may reduce food cravings as obesity treatment
Minimising exposure to common hormone-disrupting chemicals may reduce obesity rates
Could intermittent fasting diets increase diabetes risk?
Brain development disorders in children linked to common environmental toxin exposures
Children born to mothers with low vitamin D levels may develop autism-like behaviours
Over-the-counter antihistamines linked to impaired fertility in men
Arthritis drug can lower sugar levels in diabetes
Potential new target for reducing osteoporosis risk in men
Successful male infertility treatment does not lower fertility of sons
Warm temperatures can lead to misdiagnosis of diabetes in pregnancy
Guidelines for management of recurrent pituitary tumours recommend new drug as first line treatment
Taking paracetamol during pregnancy may reduce fertility of daughters
Link found between morning sickness, smoking and healthy pregnancies
High fat diet during childhood may increase PCOS risk later in life
Early pregnancy test for cows improves welfare and food production
International collaboration release revised guideline for improved management of Turner syndrome
Treating PCOS with a combination of oral contraceptives and spironolactone does not increase the risk of diabetes or heart disease
Vitamin D supplements could help pain management
Breast cancer risk is more affected by total body fat than abdominal fat
New nanotechnology application for difficult-to-treat cancers
Just six months of frequent exercise improves men’s sperm quality
Consuming more than two soft drinks a day can double risk of diabetes
Age-related scarring in ovaries may explain reproductive decline
Happy cows make more nutritious milk
Third of pregnant women iron deficient; risk thyroid-related pregnancy complications
New recommendations for the diagnosis and treatment of Adrenal Incidentalomas published in the European Journal of Endocrinology
Sitting down for long periods when pregnant linked to weight gain and depression
New drug provides safer alternative to conventional IVF treatment
Enzyme potential target for fight against obesity and diabetes
Bursts of high-intensity exercise could help diabetes patients manage low blood sugar levels
Soybean foods may protect menopausal women against osteoporosis
Vitamin D pill a day may improve exercise performance and lower risk of heart disease
Diabetes associated with increased risk of serious bacterial blood infection
Breast cancer risk higher in women with overactive thyroid
Injection of appetite gene may offer a more effective alternative to dieting
Hyperthyroidism could be great cost to countries in disability benefits
Mother’s hormone levels predict child’s ability to do maths