older horse in pasture

Horses have higher concentrations of certain inflammation-related proteins in their blood as they age, a finding that provides further molecular evidence of inflammaging—age-related bodywide inflammation—according to an equine research group in Italy.

The scientists found serum concentrations of certain key acute-phase proteins were higher in older horses than younger ones, suggesting aging horses might have increased acute phase responses—meaning more inflammation—than their younger counterparts, said Giuseppe Piccione, PhD, DVM, a professor in the University of Messina’s Faculty of Veterinary Medicine, and his research colleague Francesca Arfuso, BSci, PhD.

These findings might provide useful information about what’s occurring at a microscopic level in equine seniors and why, they said.

“Improved knowledge of key inflammatory biomarkers and their pathways during aging may support future biomedical interventions to modulate their activity to improve welfare and safeguard health status of the horse,” said Arfuso.

Acute-Phase Proteins and Horse Health

In the earliest stages of infection or injury, the body reacts by triggering a general immune response called the acute-phase response, Arfuso said. Unlike the more refined and targeted immune response that usually begins several hours or days later, this initial response primarily involves inflammation. It starts with the release of soluble mediators such as cytokines, acute-phase proteins (APPs), and chemokines, which promote the migration of neutrophils and macrophages (two types of white blood cells) to the infection/injury location to create an unfavorable environment for disease-causing organisms.

During an acute-phase response, the liver produces two main kinds of APPs: positive APPs, which increase in blood serum in response to inflammation, infection, injury, and stress; and negative APPs, which decrease in these conditions. Positive APPs include mostly alpha-globulins (α-globulins)—especially C-reactive protein (CRP), which is one of the most strongly reacting known APPs in both humans and animals, the researchers said. The most notable negative APP, meanwhile, is albumin.

While equine veterinarians routinely examine these inflammation marker concentrations as they relate to various pathologic (disease- or damage-causing) backgrounds, “the influence of age on the serum values of CRP together with electrophoretic protein patterns has not been well described in horses,” Piccione, Arfuso, and their study collaborators wrote.

Investigating Acute-Phase Proteins in Different Age Groups of Horses

Wondering what these proteins might reveal about inflammaging in horses, Piccione, Arfuso, and their fellow researchers took resting blood samples from 30 healthy Italian saddle horses aged 2 to 20 years, all living at the same training center in Sicily. They divided the horses into groups according to age: young (2 to 4 years); middle adult (7 to 10 years); and late-middle adult (15 to 20 years). The groups included equal numbers of mares and geldings. The late-middle adults were no longer in training, and none of the younger horses had trained within two weeks of the study, they said.

Using enzyme-linked immunosorbent assays (ELISA), spectrophotometers, and electrophoresis, the researchers reported they found the horses’ serum concentrations of CRP and other globulins of type α1 and α2 increased with age.

By contrast, albumin and the albumin-to-globulin ratio were lower in both groups of adults than in the young horses.

They found no other significant age-related differences in the blood parameters they investigated.

Protein Concentrations in Horses’ Blood Support Inflammaging Theory

The fact that age influenced the horses’ main APPs suggests an increased acute-phase response in aging horses, the researchers said.

“This inflammaging process is part of the phenomenon of immunosenescence, including the normal fluctuations resulting from an aging immune system,” they said in their study report.

“This age-dependent immunosenescence process ultimately results in the body becoming increasingly worse at controlling or downregulating the production of pro-inflammatory proteins during and after immune responses,” they continued. “Consequently, a progressively higher inflammatory state is observed in many aging tissues.”

The team said future studies are needed assessing APPs in horses aged 21 and older, along with investigations to assess whether other APPs might be involved in equine inflammaging.

The study, Serum C-reactive protein and protein electrophoretic pattern correlated with age in horses, was published in the Journal of Equine Veterinary Science in May 2023.