Anorexia of Ageing

Definition. In many older adults the decrease in energy intake is greater than the decrease in energy expenditure, so body weight is lost. This physiological, age-related reduction in energy intake is termed the anorexia of ageing (Morley, 1997).

It is a geriatric syndrome. Pathy’s depicts it as a multifactorial geriatric syndrome with poor outcomes, arising from four groups of factors — physiological changes, changes due to chronic disease, social determinants/environment, and iatrogenic causes/polypharmacy.

Physiological vs pathological. The physiological component is intrinsic to ageing; the pathological component (disease, drugs, depression, dementia) is superimposed and is at least partly treatable — hence recognition matters.

Magnitude of intake decline. Energy intake falls by ~30% between ages 20 and 80. NHANES III: decline of 1321 kcal/day in men and 629 kcal/day in women. New Mexico longitudinal study: −25.1 kcal/day/year in men, −19.3 in women. Swedish cohort (ages 70→76): −610 kcal/day in men, −440 in women. Older people eat smaller meals, more slowly, with fewer snacks, and consistently report less hunger.

Prevalence. Anorexia occurs in 3.3% of community-dwelling elders rising to 33% in nursing homes. About 16– 18% of community elders consume <1000 kcal/day. Loss of appetite is the single key predictor of malnutrition in older adults.

(i) Loss of homeostatic regulation. In Roberts’ classic experiment, young and old men were underfed by ~750 kcal/day for 21 days; on refeeding ad libitum, young men over-ate and regained weight, whereas old men returned only to baseline intake and never regained the lost weight. Consequently, after an anorectic insult (e.g. surgery), older adults stay undernourished longer and are more susceptible to superimposed illness.

(ii) The ageing gut. Cell loss in the oesophageal myenteric plexus and slowed visceral nerve conduction reduce sensory feeding stimuli. Impaired receptive relaxation of the gastric fundus — possibly due to increased fundic nitric oxide — causes more rapid antral filling and distension → earlier satiety, and contributes to slower gastric emptying; postprandial hunger is inversely related to the rate of gastric emptying.

(iii) Declining senses. Smell declines markedly after age 50 — over 60% aged 65–80 and over 80% aged ≥80 have major reductions (thinning epithelium, reduced mucus, poor regeneration of olfactory receptor cells). 46% of older adults with olfactory dysfunction report a change in appetite or weight. Ageing also reduces sensory-specific satiety (the normal decline in pleasantness of a food after eating it), favouring a less varied, monotonous diet and hence micronutrient deficiency.

(iv) Central neurotransmitters. Noradrenaline stimulates, serotonin inhibits, and dopamine has region-specific effects on feeding. Ageing is associated with increased satiating effects of serotonin, without clear changes in dopamine or noradrenaline.

Opioids — reduced feeding drive. Elderly patients with idiopathic senile anorexia have lower plasma and CSF β-endorphin than age-matched controls. Morphine increases food intake in young but not old mice; naloxone reduces intake in young but not old rats; older men are less sensitive to naloxone’s inhibitory effect on fluid intake. The stimulatory opioid drive declines with age.

Cholecystokinin (CCK) — the strongest candidate. CCK is a physiological satiety hormone released by intestinal fat and protein, which also slows gastric emptying. Plasma CCK is higher in healthy older than young adults, and significantly higher in elderly people with idiopathic anorexia. Crucially, IV CCK-8 suppressed food intake twice as much in older than young adults (31% vs 15%, p = 0.02). The combination of higher levels plus enhanced sensitivity suggests CCK may cause the anorexia of ageing and raises the possibility of CCK antagonists as therapy.

Other gut peptides — largely negative evidence. GLP-1: increases fullness and reduces intake; ageing studies show no change or increased levels — unproven as a cause. PYY: reduces intake by ~30% acutely, but no difference in fasting or postprandial PYY between young and old — no convincing role. Ghrelin: the only orexigenic gut hormone; the effect of healthy ageing on circulating ghrelin is unclarified Nutrition in the Elderly — MD Geriatric Medicine Revision Page 15 of 25 but probably minimal; ghrelin resistance may occur (older subjects are less sensitive to its GH-releasing effect). Ghrelin is positively associated with testosterone, so falling androgens may lower it. Insulin: rises with ageing, but this is mainly due to adiposity-related insulin resistance; peripheral insulin infusion does not alter appetite — unlikely to contribute.

NPY, galanin, orexins and CART. NPY strongly stimulates feeding and falls with age in male rodents, but human data show increased, not decreased, NPY — hence no convincing human role. Galanin levels are unchanged. Orexin A levels actually increase with age. CART (inhibitory) rises in old male rats, mediated by the age-related fall in testosterone — but human data are absent.

Leptin and testosterone. Leptin suppresses appetite and rises with fat mass. In men — but not women — ageing raises leptin even after adjusting for fat mass, because of the age-related fall in testosterone (leptin is inversely related to testosterone). Leptin resistance may also develop with age. Testosterone therapy in frail older men improves muscle strength, grip, function and rehabilitation outcomes (Amory, Bakhshi, Srinivas-Shankar) and reduced hospitalisation when combined with a nutritional supplement (Chapman) — but does not reliably increase appetite.

Cytokines — “ageing as a form of stress.” IL-1, IL-6 and TNF-α reduce food intake and body weight via central and peripheral pathways and are raised in cancer/AIDS cachexia. Ageing produces stress-like hormonal changes — raised cortisol and catecholamines, falling sex hormones and growth hormone. Cortisol and catecholamines stimulate IL-6 and TNF-α, while sex hormones inhibit IL-6. Plasma IL-6 rises with normal ageing and correlates inversely with functional ability; raised CRP and cytokine receptors independently predict physical dysfunction.

Chronic disease. Depression (2–10% in community, far more in institutions — the commonest treatable cause; treating it produces weight gain), dementia (~2-fold risk of anorexia; up to 50% of institutionalised dementia patients have PEM; apraxia of swallowing, pocketing, spitting; weight loss may precede dementia as a preclinical marker), COPD (catabolic state, nicotine, opioids, dysmotility), CHF (anorexia in >40% of end-stage; raised catecholamines, cortisol, renin, aldosterone; hypoxia-driven TNF-α → raised leptin), CKD (30–40% of dialysis patients, with four-fold increased mortality; uraemic toxins; more frequent haemodialysis improves appetite), plus cancer, rheumatoid arthritis, infection, hyperthyroidism and malabsorption.

Physical, social and iatrogenic factors. Poor dentition and ill-fitting dentures (denture wearers had poorer protein intake), dysphagia, immobility (stroke), tremor (Parkinson’s), poor vision; poverty and food insecurity; ~29.3% of non-institutionalised elders live alone, and older people eat up to 50% more in company than alone; institutions often fail to cater to ethnic food preferences. Iatrogenic: more than 250 prescribed drugs alter taste; digoxin and chemotherapy cause nausea and anorexia; aluminium/magnesium antacids deplete phosphate and potassium; penicillamine causes zinc depletion and loss of taste acuity; high-fibre diets cause early satiety.

Consequences. Anorexia of ageing leads to impaired muscle function (↓mass, strength, relaxation), decreased bone mass and fracture risk, immune dysfunction and infection, anaemia, poor wound healing, cognitive impairment, delayed recovery from surgery, more falls, more admissions, longer stays and increased mortality. Protein-energy malnutrition is a strong independent predictor of mortality in community, nursing-home, hospital and recently discharged elders, and the risk is amplified by renal failure, cardiac failure and cerebrovascular disease.

Assessment. Screen appetite with the SNAQ — four items on appetite, early satiety, taste of food and number of meals, scored 1–5; a score <14 indicates significant risk of weight loss. Also use MNA/MNA-SF item A (decline in food intake over 3 months). Differentiate from cachexia (inflammation-driven, CRP raised), starvation, primary depression, malabsorption and hyperthyroidism. Apply the “MEALS ON WHEELS” mnemonic to uncover treatable causes.

Management. First, treat the pathological component: depression, dementia-related feeding problems, drugs, dentition, dysphagia, constipation, pain, infection, thyroid disease. Food-first measures: flavour enhancement (improves intake and nutritional status in nursing-home residents), eating in company, small frequent nutrient-dense meals, texture modification, oral and dental care, feeding assistance, meals-on-wheels. Oral nutritional supplements — mortality benefit when ≥400 kcal/day for ≥35 days in malnourished, unwell elders aged ≥75. Resistance exercise — the primary intervention for the associated sarcopenia. Nutrition in the Elderly — MD Geriatric Medicine Revision Page 16 of 25 Orexigenic drugs (palliative only): megestrol acetate is the most studied (increases appetite, weight and quality of life; oedema the significant adverse effect); corticosteroids improve appetite without weight gain; cyproheptadine increases appetite without weight gain; cannabinoids (dronabinol, nabilone) and thalidomide (anti-TNF) have limited evidence. CCK antagonists remain theoretical.

Prevalence now quantified globally. A meta-analysis of 36 studies found the overall pooled prevalence of anorexia of ageing to be 22.7% with an incidence of 3.78%, stable from 2011 to 2024; the highest prevalence was in inpatients at 34.7%, the most-used tool was the SNAQ, and the authors concluded that a global consensus on diagnosis is needed. (Maturitas. 2025.)

SNAQ-based estimates are higher still. Across 62 studies from 24 countries (n = 80,176), the pooled prevalence of anorexia/appetite loss was 29% (95% CI 26–34%), ranging from 22% in South America to 55% in Africa; by setting it was 25% in the community, 38% in nursing homes and 42% in hospitals, and higher rates were associated with female sex, lower educational level, eating alone, oral problems and depression. Note how the “eating alone” and “oral problems” findings validate the textbook’s social and dental factors. (Li W, et al. Age Ageing. 2025;54:afaf249.)

Formal link with frailty. In a systematic review of 4,657 community-dwelling older adults, anorexia of ageing was present in 11.3% overall but in 20.5% of frail and pre-frail participants; robust status was associated with a 63% lower probability of concomitant anorexia of ageing (OR 0.37, 95% CI 0.21–0.65, p = 0.0005). (Nutrients.

Ghrelin agonism has become a real therapy. Anamorelin, an oral ghrelin receptor agonist, was approved in Japan in 2021 for cancer cachexia in lung, gastric, colorectal and pancreatic cancers, acting mainly through stimulation of growth hormone secretion and appetite enhancement. In several randomised, double-blind, placebo-controlled trials it significantly improved lean body mass and appetite in cancer cachexia. Examination point: the textbook’s proposed ghrelin/CCK pathways have now produced a licensed drug. (Anticancer Res. 2025;45:865; eClinicalMedicine.

GDF-15 identified as a new driver of anorexia-cachexia. In a phase 2 randomised double-blind 12-week trial, patients with cancer cachexia and elevated GDF-15 (≥1500 pg/mL) receiving ponsegromab, a humanised anti-GDF-15 monoclonal antibody, had significantly greater weight gain than placebo — a median between-group difference of 2.81 kg in the 400-mg group — with improvements in appetite, cachexia symptoms and physical activity, confirming GDF-15 as a driver of cachexia. This is a mechanism not present in the textbook at all. (Groarke JD, et al. N Engl J Med. 2024;391:2291–2303.)

Mirtazapine — promising in oncology, disappointing in geriatrics. A randomised trial supported mirtazapine as an appetite stimulant in NSCLC-related anorexia (JAMA Oncol 2024), but in a multi-site propensity-matched cohort of adults ≥65 started on mirtazapine 7.5 mg, appetite improvement did not differ from controls (20% vs 23%; OR 0.89, 95% CI 0.43–1.82), mean weight change was −1.22 kg, and oversedation prompted discontinuation in 6.3%. (JAMA Oncol. 2024;10:305–314; companion geriatric cohort. 2026.)

Cannabinoids should not be recommended. Randomised controlled trials and meta-analyses in patients with cancer showed that medicinal cannabis did not improve appetite or weight gain, and in the absence of high-quality evidence cannabinoids cannot presently be recommended for cancer-associated cachexia. (J Thorac Dis. 2025;17:3478– 3483.)

Megestrol is now contraindicated in older adults. The 2023 AGS Beers Criteria grades it avoid (strong recommendation, moderate quality) — minimal effect on weight, with increased risk of thrombotic events and possibly death in older adults. (AGS Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2023;71.)

Screening is now mandated. ESPEN recommends that all older persons shall routinely be screened for malnutrition to identify existing risk early, with oral intake supported by nursing interventions, education, nutritional counselling, food modification and oral nutritional supplements. A dedicated ESPEN dementia update followed in 2024. (Volkert D, et al. Clin Nutr. 2022;41:958–989; Volkert D, et al. Clin Nutr. 2024.)

A new iatrogenic cause — the GLP-1 era. The textbook lists GLP-1 as an unproven endogenous contributor; exogenous GLP-1 receptor agonists are now a common prescribed cause of anorexia and weight loss in older adults, with concomitant muscle mass loss raising concerns about sarcopenia and sarcopenic obesity. (Curr Nutr Rep. 2026.)