The Ageing Adipose Paradox: Implications for Metabolic Health.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Preadipocyte commitment to the adipogenic lineage declines markedly with advancing age, while triglyceride accumulation in hypertrophied existing adipocytes persists or expands. This creates a dissociation between adipogenic capacity and lipid-buffering demand, progressively weakening depot metabolic competence and contributing to systemic insulin resistance. This review examines the molecular mechanisms linking impaired adipose tissue plasticity during ageing to metabolic decline, and appraises therapeutic strategies that may restore adipose progenitor competence or limit downstream metabolic dysfunction. Ageing adipose tissue is characterized by four interlocking defects. First, transcriptional reprogramming, including induction of the inhibitory CCAAT/enhancer-binding protein β-LIP isoform through CUG triplet repeat-binding protein 1, together with reduced C/EBPα and peroxisome proliferator-activated receptor γ activity, shifts progenitors away from differentiation and toward hypertrophic lipid storage. Second, SIRT7 opposes SIRT1 in regulating adipogenic commitment, implicating sirtuin and NAD + dysregulation in the age-related adipogenic deficit. Third, nuclear lamina remodelling restricts chromatin accessibility at adipogenic loci. Fourth, senescent cells accumulate in ageing depots and generate a senescence-associated secretory phenotype enriched in interleukin-6, tumour

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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