How Inflammaging Drives Age-Related Obesity in Cats — and What It Reveals About Human Aging

Aging fundamentally disrupts the body's ability to resolve inflammation, tipping the balance toward a persistent low-grade pro-inflammatory state called inflammaging. First coined by Franceschi et al. in 2000, inflammaging is driven largely by the senescence-associated secretory phenotype (SASP) — a dynamic secretome released by senescent cells that includes pro-inflammatory cytokines (notably IL-6 and IL-8), chemokines, matrix metalloproteases, growth factors, and extracellular vesicles. SASP regulation occurs at transcriptional and post-transcriptional levels, with NF-κB serving as the master regulator. The mature SASP phase is reached within 4–10 days of DNA damage induction and, when chronically sustained, disrupts tissue function and accelerates aging pathologies including obesity, type 2 diabetes, cardiovascular disease, neurodegeneration, and certain cancers.

Cats are highlighted as a particularly relevant model for studying age-related metabolic disease because their glucose and lipid metabolism diverges significantly from dogs and parallels human susceptibility. Feline livers lack glucokinase — the rate-limiting glycolytic enzyme — while gluconeogenic enzyme activity is paradoxically elevated. Critically, cats basally express significantly lower mRNA levels of key insulin signaling components including IRS-1, IRS-2, and PI3K P-85α compared to dogs, and expression of IRS-2 and PI3K mRNA decreases further in obese cats' liver and skeletal muscle. Adiponectin, the anti-inflammatory insulin-sensitizing adipokine, is already lower in cats at baseline and falls further with weight gain, making cats inherently predisposed to insulin resistance and visceral obesity.

Obesity prevalence in cats is estimated at 30–40%, rising with age — mirroring human obesity epidemics. The review draws on studies using Body Condition Score (BCS) as the primary assessment tool, a 9-point scale where 5 is ideal and 9 is severely obese. Severely obese cats (BCS 9) exhibit excessive visceral fat accumulation with significantly increased plasma concentrations of triglycerides, free fatty acids, and TNF-α, alongside a significant decrease in adiponectin. Adipose tissue mRNA expression of lipogenic genes FAS and SREBP-1 is significantly elevated in obese cat abdominal fat and liver, accelerating ectopic lipid deposition. Aged obese cats consistently show fatty liver and enlarged adipocytes with macrophage infiltration — histological hallmarks of inflammaging-driven metabolic dysfunction.

Table 2 in the review consolidates the adipokine and cytokine profile shifts in obese cats across multiple studies: adiponectin is consistently decreased; leptin, resistin, TNF-α, IL-1β, IL-6, MCP-1, SAA, FFA, and triglycerides are all elevated. Serum amyloid A (SAA), an acute-phase reactant increasingly implicated in chronic metabolic disease and autoimmune conditions, is positively associated with visceral adiposity, suggesting visceral fat as a major SAA source — a direct SASP manifestation. These circulating adipokine shifts are explicitly characterized by the authors as SASP in action.

The review closes by emphasizing that while aging is inevitable, the onset of age-related disease can be delayed through early intervention. Adequate nutrition (macronutrient composition appropriate for obligate carnivores), moderate exercise to preserve lean mass and metabolic rate, and psychological enrichment to reduce stress-induced cortisol-driven adipogenesis are identified as the primary levers. The authors frame cats not merely as veterinary patients but as valuable translational models for investigating human inflammaging and metabolic syndrome, given their spontaneous development of obesity, insulin resistance, and fatty liver with age — without requiring genetic manipulation.