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VOL. 8, ISSUE 3 (2026)
Metabolic remodeling and multi-system health management in middle-aged and older adults: Pathophysiology and clinical evidence
Authors
Lung Tan Lu
Abstract
Against the backdrop of global population ageing, the metabolic
transition occurring after age 45 represents a critical biological window
shifting the human body from homeostasis to multi-system decompensation. This
systemic remodeling is driven by basal metabolic shifts, skeletal muscle
anabolic resistance, endocrine axis alterations, mitochondrial attrition, gut
microbiota dysbiosis, and inflammaging. These factors sequentially induce
insulin resistance, glucolipid disturbances, hyperuricemia, metabolic dysfunction-associated
steatotic liver disease (MASLD), chronic kidney disease (CKD), and sarcopenic
obesity, amplifying risks of disability and mortality. While traditional models
assumed a linear decline in basal metabolism, recent doubly labeled water studies
reveal that total energy expenditure remains stable between ages 20 and 60,
with significant decline initiating only post-60 at roughly 0.7% annually.
Nonetheless, latent pathological changes—including ectopic visceral fat
accumulation and subclinical inflammation—accumulate during middle age,
erupting later in life. Synthesizing landmark trials (e.g., DPP, IMPROVE-IT,
DAPA-CKD, CANTOS, CALERIE) alongside high-quality cohorts and meta-analyses,
this review examines the underlying mechanisms, screening thresholds, and
risk-stratified interventions across six core axes: glucose, lipids, uric acid,
thyroid, liver, and kidney. We further dissect skeletal muscle–bone coupling,
mitochondrial ageing, SASP, and inflammaging cross-tissue networks. Based on these
findings, we establish an integrated management framework centered on
"stratified assessment, precision intervention, and dynamic
monitoring," prioritizing lifestyle foundations, risk stratification, and
the preservation of functional independence. An expert commentary outlines
real-world clinical dilemmas, Asian population localization challenges, and
overdiagnosis risks. Finally, we discuss translational prospects for
anti-ageing therapeutics, senolytics, and microbiota interventions, delivering
high-level evidence to support clinical practice in geriatrics, endocrinology,
and public health policy.
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Pages:89-96
How to cite this article:
Lung Tan Lu "Metabolic remodeling and multi-system health management in middle-aged and older adults: Pathophysiology and clinical evidence". International Journal of Medical Science and Clinical Research, Vol 8, Issue 3, 2026, Pages 89-96
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