“Inflammaging” represents a chronic, sterile, low-grade inflammatory state associated with biological aging. It has been extensively studied in humans and is of recent interest in small animals, particularly dogs. Dogs share the same environment as their owners but have a shorter lifespan, making them particularly suitable for studying specific markers as predictors of the aging process. This research helps not only to improve animal welfare in terms of “healthspan” but also to gain further insight into managing chronic inflammation in humans, in line with the “One Health” approach. This observational study aimed to evaluate the longitudinal trend of serum haptoglobin concentration in a heterogeneous dog population to investigate a possible correlation with advancing age, independent of other concurrent clinical conditions. Initially, 209 dogs aged 5 to 16 years old, varying in breed, size and sex, were included; they underwent clinical assessment and blood sampling at baseline (T_0) and after an 18-month follow-up (T_3,n=165). Additionally, two subgroups were identified: one comprising clinically healthy patients (T_0: n=108;〖 T〗_3: n=62), excluding animals with obesity, severe tartar, chronic inflammatory or dermatological diseases, or osteoarthritis, and another comprising subjects not receiving anti-inflammatory or immunomodulatory drug therapies (T_0:n=168; T_3:n=132). Linear regression models and tests for paired data were used to investigate potential associations. At both T_0 and T_3, a statistically significant positive correlation (p<0.001) was observed between increasing age and haptoglobin levels; this association was more marked in the subgroup of healthy dogs and even more pronounced in the subgroup of untreated subjects. The 18-month longitudinal analysis confirmed a significant increase in the biomarker across the total population and a clear upward trend in healthy subjects, despite wide individual variability. Haptoglobin levels also showed a significant increase in patients not receiving therapeutic treatment. The multiple regression model validated age as an independent positive predictor (p<0.001) relative to the included comorbidities; among these, only the presence of severe tartar showed a borderline association. At the conclusion of the study, it is evident that serum haptoglobin concentration increases progressively with advancing age in dogs, independently of concurrent diseases. This allows us to validate haptoglobin as a robust systemic biomarker of “inflammaging” in the canine species.
L'inflammaging rappresenta uno stato infiammatorio cronico, sterile e di basso grado correlato all'invecchiamento biologico, tanto studiato in campo umano e di recente interesse anche nei piccoli animali, in particolare nel cane. Quest'ultimo, infatti, condivide lo stesso ambiente del proprietario, ma presenta una lunghezza di vita inferiore, rendendolo particolarmente adatto allo studio di determinati marcatori come predittori del processo di “aging”. Tutto questo aiuta non solo a migliorare il benessere animale in termini di "healthspan", ma anche a comprendere ancor di più come agire sull'infiammazione cronica nell'uomo secondo l'approccio di "One Health". Il seguente studio osservazionale ha lo scopo di valutare l’andamento longitudinale della concentrazione sierica di aptoglobina in una popolazione di cani eterogenea, al fine di indagare una possibile correlazione con l'avanzare dell'età, indipendentemente da altre condizioni cliniche concomitanti. Sono stati inclusi inizialmente nello studio 209 cani tra i 5 e i 16 anni, di varie razze, taglie e sesso, e sono stati sottoposti a valutazione clinica e prelievo ematico al tempo basale (T_0) e dopo 18 mesi (T_3,n=165). Sono stati, inoltre, isolati due sottogruppi di soggetti: uno comprendente i pazienti clinicamente sani (T_0: n=108; T_3: n=62), escludendo gli animali affetti da obesità, grave tartaro, patologie infiammatorie croniche e di tipo dermatologico, o osteoartrosi; l’altro comprendente soggetti non sottoposti a terapie farmacologiche antinfiammatorie o immunomodulanti (T_0:n=168; T_3: n=132). Sono stati utilizzati modelli di regressione lineare e test per dati appaiati al fine di indagare le possibili associazioni. Sia a T_0 che a T_3, è stata osservata una correlazione positiva statisticamente significativa (p<0,001) tra l’aumento dell’età e i livelli di aptoglobina, con un legame più marcato nel sottogruppo dei cani sani, e ancora più pronunciato nel sottogruppo dei soggetti non trattati. L’analisi longitudinale a 18 mesi ha confermato un incremento rilevante del biomarcatore nella popolazione totale e un chiaro trend di aumento nei soggetti sani, nonostante sia stata riscontrata un’ampia variabilità individuale. Anche nei pazienti esenti dai trattamenti terapeutici l’aptoglobina ha mostrato un incremento significativo. Il modello di regressione multipla ha validato l’età come predittore positivo indipendente (p<0,001) rispetto alle comorbilità tenute in considerazione, tra le quali solo la presenza di grave tartaro ha evidenziato un’associazione, di tipo borderline. Al termine dello studio risulta evidente che la concentrazione sierica di aptoglobina aumenta in modo progressivo all’avanzare dell’età del cane, indipendentemente dalle patologie concomitanti. Questo ci permette di validare l’aptoglobina come solido biomarcatore sistemico di inflammaging nella specie canina.
Valutazione dell'aptoglobina come indicatore di inflammaging nella specie canina
SEVERINO, MIRIAM
2025/2026
Abstract
“Inflammaging” represents a chronic, sterile, low-grade inflammatory state associated with biological aging. It has been extensively studied in humans and is of recent interest in small animals, particularly dogs. Dogs share the same environment as their owners but have a shorter lifespan, making them particularly suitable for studying specific markers as predictors of the aging process. This research helps not only to improve animal welfare in terms of “healthspan” but also to gain further insight into managing chronic inflammation in humans, in line with the “One Health” approach. This observational study aimed to evaluate the longitudinal trend of serum haptoglobin concentration in a heterogeneous dog population to investigate a possible correlation with advancing age, independent of other concurrent clinical conditions. Initially, 209 dogs aged 5 to 16 years old, varying in breed, size and sex, were included; they underwent clinical assessment and blood sampling at baseline (T_0) and after an 18-month follow-up (T_3,n=165). Additionally, two subgroups were identified: one comprising clinically healthy patients (T_0: n=108;〖 T〗_3: n=62), excluding animals with obesity, severe tartar, chronic inflammatory or dermatological diseases, or osteoarthritis, and another comprising subjects not receiving anti-inflammatory or immunomodulatory drug therapies (T_0:n=168; T_3:n=132). Linear regression models and tests for paired data were used to investigate potential associations. At both T_0 and T_3, a statistically significant positive correlation (p<0.001) was observed between increasing age and haptoglobin levels; this association was more marked in the subgroup of healthy dogs and even more pronounced in the subgroup of untreated subjects. The 18-month longitudinal analysis confirmed a significant increase in the biomarker across the total population and a clear upward trend in healthy subjects, despite wide individual variability. Haptoglobin levels also showed a significant increase in patients not receiving therapeutic treatment. The multiple regression model validated age as an independent positive predictor (p<0.001) relative to the included comorbidities; among these, only the presence of severe tartar showed a borderline association. At the conclusion of the study, it is evident that serum haptoglobin concentration increases progressively with advancing age in dogs, independently of concurrent diseases. This allows us to validate haptoglobin as a robust systemic biomarker of “inflammaging” in the canine species.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/114401