Aging in humans is associated with chronic low-grade inflammation (systemic), and this condition is sometimes referred to as “inflammaging”. In general, canines also age similarly to humans, and such aging is associated with a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Each of these conditions is also associated with an increase in pro-inflammatory cytokines. An inflammatory state characterized by an increase in pro-inflammatory markers including but not restricted to tumor necrosis factor-α, interleukin-6, IL-1β, and C-reactive protein (CRP) is believed to contribute to or worsen a general decline in biological mechanisms responsible for physical function with aging. Nutritional management of inflammation in aging dogs is important in maintaining health. In particular, natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and, when included in the diet, may contribute to a reduction in inflammation. While there are scientific data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals, the clinical data are limited and more studies are needed to validate the efficacy of these ingredients. This review will summarize the role of dietary ingredients in reducing inflammatory molecules as well as review the evidence available to support the role of diet and nutrition in reducing chronic low-grade systemic inflammation in animal and human studies with a special reference to canines, where possible.

Chronic low-grade inflammation is a key contributor to the progression of kidney disease. The release of cytokines and other pro-inflammatory proteins may further contribute to detrimental kidney health by increasing interstitial edema and renal fibrosis. The aim of the present study was to investigate the inflammatory markers in canines who developed renal disease naturally and were diagnosed with renal disease either during life or following necropsy, as assessed by a veterinarian. RNA was isolated from canine blood obtained at necropsy and stored as bioarchived samples from ten canines with renal disease (9.6–14.7 yr) and ten controls (10.1–14.8 yr). At the time of death, the mean blood creatinine concentration and BUN were elevated in dogs with renal disease compared to control (both p < 0.01). Samples were assessed for changes in gene expression using the Canine cytokine RT² Profiler PCR Array for inflammation. There was a significant increase in C-C Motif Chemokine Ligand 16 (CCL16), C-X-C Motif Chemokine Ligand 5 (CXCL5), Interleukin 16 (IL-16), and Complement Component 5 (C5) (all p < 0.05 vs. con). In addition, there was also a statistically non-significant increase in 49 genes and a down-regulation in 35 genes from a panel of total 84 genes. Pro-inflammatory genes including CCL16, CXCL5, IL-16, and C5 can all contribute to renal inflammation and fibrosis through different signaling pathways and may lead to a progressive impairment of kidney function. Blockade of their activation may be important in ameliorating the initiation and/or the progression of renal disease.

One of the significant organ systems which decline in aging is the kidney. While the causes of age-associated decline in renal function are likely multifactorial, oxidative stress and inflammation are hypothesized to play important roles in the structural and functional changes of the kidney. During aging there is a general decline in the glomerular filtration rate (GFR), a primary measurement used to assess kidney function. Inflammation and oxidative stress have been hypothesized to have a significant detrimental effect on renal function in aging and this may be attenuated by renal protective dietary ingredients. These dietary ingredients may affect renal function directly or through a microbiome-mediated secondary product. Likewise, structural changes including renal tubular atrophy, interstitial fibrosis, and glomerulosclerosis have all been described in aging. Such detrimental changes may benefit from dietary ingredients that may delay or attenuate the occurrence of such changes. This review will describe the physiology and pathophysiology of aging in renal function with an emphasis on dogs and cats that develop a decline in kidney function naturally. In addition, the varying biomarkers of health and renal dysfunction will be discussed. Finally, we will evaluate the aid in the management of this normal decline through dietary intervention in animal models.

The need to maintain body lean as cats age is shown in both health and disease. In healthy cats, body lean is associated with enhanced movement and overall longevity. In many disease states (i.e., renal disease, obesity), an enhanced or minimally maximal support of body lean is associated with quality of life and is a nutritional goal in aiding in the management of the disease. This study was designed to investigate the effect of these two dietary components and their combination on body composition and circulating factors of health, including metabolomics analysis and cytokine concentration. The foods that were fed for 169 days to four groups of cats and consisted of control food (formulated to meet the nutritional needs of all adult cats), carnitine-enhanced food (control food plus 300 mg/kg L-carnitine), carnosine-enhanced food (control food plus 1000 mg/kg carnosine), and food enhanced with both (control plus 300 mg/kg carnitine and 1000 mg/kg carnosine). Dietary enhancement with L-carnitine and carnosine increased body lean at the end of the study compared to the cats consuming the control food or the combination food. The cats consuming L-carnitine alone had a decreased concentration of circulating cytokines, while those consuming the combination food had an increased concentration of glucose, pyruvate, succinate, and circulating cytokines.

This study used thirty-two dogs, which were assigned to a preferred period of 14 days and then assigned to one of the four treatment foods: control (containing no added betaine, no added L-carnitine), control with 0.5% added betaine (Treatment 2), control with no added betaine and 300 ppm added L-carnitine (Treatment 3), or control with 0.5% added betaine and 300 ppm added L-carnitine (Treatment 4). All treatment foods were fed for ninety days. Untargeted blood metabolomic analysis and immune response were measured at the beginning and end of the 90-day feeding trial. Feeding betaine increased single-carbon metabolites while decreasing many carnitine-containing metabolites. Feeding L-carnitine increased many carnitine metabolites, while the combination synergistically influenced the metabolome. The combination of betaine and L-carnitine increased the cytokines released in a Tru-culture system in response to stimulation while numerically decreasing their release when unstimulated. Therefore, the combination of dietary betaine and L-carnitine could have the dual positive effects of reducing cytokine stimulation, controlling inflammation during health, and providing a robust response to bacterial infection.

Background: Ketogenic foods limit digestible carbohydrates but contain high fat, and have antioxidant and anti-in fl ammatory effects as well as improving mitochondrial function. beta-Hydroxybutyrate (BHB), 1 of the ketone bodies, reduces the proin fl ammatory NLR family pyrin domain containing 3 in fl ammasomes, as well as chemokines in cultures. Objectives: We assessed the immune -modulating effects of 2 low -carbohydrate (LoCHO) foods varying in protein and fat and compared their effects with a food replete with high -carbohydrate (HiCHO) in healthy canines. Methods: Dogs were fed control food [HiCHO; ketogenic ratio (KR: 0.46) followed by LoCHO_PROT (KR: 0.97), then LoCHO_FAT (KR: 1.63) or LoCHO_FAT followed by LoCHO_PROT. Each food was fed for 5 wk, with collections in the 5th wk; 15 wk feeding total. Gene expression for circulating in fl ammatory cytokines from 10 dogs was assessed using the Canine RT 2 Profiler polymerase chain reaction array, and fold changes were calculated using the Delta Delta Ct method. Results: LoCHO_FAT significantly increased circulating beta-hydroxybutyrate compared with both HiCHO and LoCHO_PROT. When compared with HiCHO, there was a signi fi cant decrease in several proin fl ammatory cytokines/chemokines in LoCHO_PROT and LoCHO_FAT groups, including chemokine (C -C motif) ligand (CCL)1, CCL8, CCL13, CCL17, CCL24, chemokine (C -X3 -C motif) ligand 1, chemokine (C -X-C motif) receptor 1, Interleukin-10 receptor alpha ((IL)-10RA), IL -1 receptor antagonist, IL -5, and secreted phosphoprotein 1 (all P < 0.05). Interestingly, a subset of in fl ammatory proteins that decreased in LoCHO_PROT but not in LoCHO_FAT included IL -33, IL -6 receptor, IL -7, IL -8, Nicotinamide phosphoribosyltransferase, and tumor necrosis factor (TNF) receptor superfamily member 11B. In contrast, the decrease in in fl ammatory markers in LoCHO_FAT, but not in LoCHO_PROT, included complement component 5, granulocyte colony -stimulating factor or G-CSF, interferon- gamma, IL -3, IL-10RB, IL -17C, Tumor necrosis factor superfamily (TNFSF)13, TNFSF13B, and TNFSF14. Decreased concentrations of selected cytokines indicate that both low -carbohydrate foods exert an anti-in flammatory effect and provide a strong rationale for testing their efficacy in dogs with in flammatory conditions. Conclusions: Both LoCHO_PROT and LoCHO_FAT foods might be important as part of immune -modulating therapeutic nutritional strategies to reduce in flammation to maintain health in canines. Our study identifies several in flammatory genes that are reduced when fed ketogenic food that were not previously reported.