- Open Access
Immunosenescence and inflammaging in the aged horse
Immunity & Ageing volume 20, Article number: 2 (2023)
The equine population in the United States and worldwide now includes a higher percentage of geriatric horses than ever previously recorded, and as methods to treat and manage elderly equids are developed and refined, this aging population will likely continue to expand. A better understanding of how horses age and the effect of age on immunity and disease susceptibility is needed to enable targeted preventative healthcare strategies for aged horses. This review article outlines the current state of knowledge regarding the effect of aging on immunity, vaccine responsiveness, and disease risk in the horse, highlighting similarities and differences to what is observed in aged humans. Horses show similar but milder age-related alterations in immune function to those reported in people. Decreases in lymphocyte proliferation and antibody production and diminished response to vaccination have all been documented in elderly horses, however, increased risk of infectious disease is not commonly reported. Aged horses also show evidence of a proinflammatory state (inflammaging) yet appear less susceptible to the chronic diseases of people for which inflammation is a risk factor. Information is currently lacking as to why the horse does not experience the same risk of age-related disease (e.g., cancer, heart disease, neurodegeneration) as people, although a lack of negative lifestyle habits, differences in diet, exercise, genetics and physiology may all contribute to improved health outcomes in the older horse.
Similar to demographic trends reported in both human and pet populations, the percentage of horses considered “aged” has been increasing, with estimates ranging from 22- 34% of all horses being older than 15 years of age [1, 2]. In the United States, the number of senior horses (over 20 years) has more than doubled since 1998, and has increased by 50% in the past decade . This trend is likely due to improvements in preventative healthcare as well as an increasing societal view of horses as companion animals as opposed to livestock. Routine vaccination, endoparasite control and preventative dentistry have undoubtedly been the largest contributors to improved horse health and longevity in the last century. Of particular interest in geriatric equine healthcare are methods to support and bolster effective immunity to infections while reducing incidence of inflammatory disease.
Immunosenescence is the process of immune dysfunction that occurs in humans and animals as they age, and is an important risk factor for morbidity and mortality in people. It contributes to the development of most of the chronic health conditions that affect the elderly, including cancer, heart disease, inflammatory and degenerative diseases. Furthermore, decline in immune competency is a primary contributor to the increased susceptibility of the aged to infectious pathogens and a decreased effectiveness of vaccines to protect against infections commonly observed in aged people [4, 5].
Similar to humans, age-related alterations in immune function occur in horses (Table 1). In people, age-associated changes to the immune system affect both innate and adaptive immunity, and include alterations in the composition of lymphocyte populations, immune response to provocation, and a generalized proinflammatory state . Diminished ability to respond to pathogen challenge is also observed in aged horses, but appears milder than that observed in people and specific modifications in vaccination schedule for older horses are not currently recommended. In addition, an effect of old age on risk of infectious disease has not been well documented, and very few of the most important infectious diseases in equids have increasing age as a risk factor for disease incidence or severity. It is unclear what factors are responsible for the milder age-related decline in immune function observed in horses, but the absence of known lifestyle risks for human chronic disease (such as excessive alcohol consumption, smoking, lack of physical exercise or poor diets) as well as differences in physiology are likely beneficial in the aging equid. While response to provocation appears only mildly impaired in aged horses, an enhanced inflammatory reactivity known as inflammaging, may be more of a concern in aged horses. Inflammaging may contribute to diseases common in aged equids, such as degenerative joint disease and reactive airway disease [7, 8]. Despite experiencing an age-related proinflammatory state, senior horses are far less prone to the leading causes of mortality in the aged human population, such as cancer, heart disease, cerebrovascular disease, chronic lower respiratory diseases and Alzheimer’s disease, all of which have been linked to inflammaging . Understanding these differences and similarities in aging between the species could prove informative for horses and humans alike. This article reviews the current state of knowledge regarding interactions of age on immunity, vaccine responsiveness, and disease risk in the horse, highlighting similarities and differences to immunosenescence processes observed in aged humans.
Special considerations for immunosenescence research in horses
Studies of immunosenescence in horses are complicated by a unique set of confounders, and as a result, study conclusions are often contradictory. For example, the definition of “aged” is often arbitrary in equine research, making comparisons across studies difficult. If subjects are too young, aging changes may not yet have occurred. If too old, there may be a bias towards including those animals with exceptional immune function . In aged horses of unknown age, dental wear is often utilized as a method for age approximation. This method is particularly useful for young horses still undergoing the transition from deciduous to permanent teeth, but becomes highly inaccurate in aged horses, in whom diet, veterinary dental care, and genetics may all have substantial roles in overall dental wear . The recent development of ‘epigenetic aging clocks’ in humans, mice, and equids offers a novel method for determining relative biologic age. The process of epigenetic aging uses methylation arrays to profile large numbers of CpG positions in the genome, and in human tissue samples is predictive of mortality even after adjusting for known risk factors such as chronological age, sex, smoking status, and other comorbidities [12, 13]. Epigenetic aging clocks have been developed for horses, and may offer a quantifiable method to determine relative age in individuals, compare the age-accelerating effects of common geriatric diseases, and evaluate the efficacy of interventions designed to prevent or delay immunosenescence in aged horses [14, 15].
In addition to difficulties related to defining and determining age in geriatric horses, identifying specific causes of age-induced decline in immune function is challenging. Ruling out the presence of subclinical disease is necessary but difficult in an aged population . In older horses, the high prevalence of co-morbidities that contribute to chronic, low-grade inflammation may affect studies on immunosenescence. For example, osteoarthritis or reactive airway disease, two of the most common diseases in age horses, have been largely ignored in studies of aging in horses thus far. Furthermore, endocrine and metabolic abnormalities common to old horses can strongly influence immune function. Equine pituitary pars intermedia dysfunction (PPID), a disease that affects 15–30% of horses > 20 years of age, is immunosuppressive, while equine metabolic syndrome (EMS) an equally common condition, is proinflammatory [17,18,19,20]. Ideally a strict inclusion protocol should be employed when enrolling participants into studies of aging immunity. In human immunological research, procedures have been developed , which combine history, clinical examination, and diagnostic laboratory results to recruit healthy aged subjects for study inclusion. Adoption of similar screening protocols may improve the quality of data gathered and the concordance among multiple studies in veterinary gerontology. Additionally, in equine studies, one must consider hormonal status throughout the study period, as pituitary and adrenal hormones are strong modifiers of immune function and are also often affected by common equine geriatric disorders. The marked effect of season on the output of anti-inflammatory hormones from the pituitary gland and the high prevalence of pituitary dysfunction (PPID) in the aged equine population [22,23,24,25] can greatly confound studies of age-related immune function in horses. Obesity is known to affect immunity and inflammation in horses, and failure to control for body condition score can obscure the interpretation of results [26,27,28]. Other potential confounders when assessing immune function in aged horses include diet, supplements, medications, exercise, travel, and environmental exposures of the study participants.
Age-associated changes in equine immune function
Alterations in lymphocyte subset populations as a function of age have been documented in several species including people, dogs, and rodents [29,30,31,32]. Changes documented across species include a decrease in the number of naïve T cells (CD45RA), which has been documented in multiple species [33,34,35,36,37]. The decrease in naïve T cells may be the result of thymic involution or alternatively. the consequence of chronic antigenic stimulation [38,39,40,41]. In particular, chronic infection with cytomegalovirus (CMV) is thought to play a role in the depletion of the naïve lymphocyte pool . Concurrent with loss of naïve T cells, clonal expansion of cytomegalovirus-specific CD8 memory cells has been observed in elderly primates [41,42,43]. The theory that exposure to pathogens can restructure the immune system even in the absence of clinical disease is supported by studies of CMV infection in specific-pathogen-free mice, where CMV infection resulted in reduced T cell responses and vaccination efficiency as well as accelerate accumulation of effector memory CD8 T cells [44, 45]. At this time, the lack of antibodies capable of differentiating equine naïve T-cells from memory T-cells has hindered studies investigating age-associated changes to T cell populations in the horse.
Other findings in human leukocyte populations include alterations in the total number of lymphocytes, CD4, CD8, T- regulatory cells, and B-cells as well as CD4:CD8 ratio [46,47,48]. Several studies have confirmed similar findings in aged horses and ponies [49,50,51,52,53,54]. The total number of lymphocytes, CD4, CD8, T-regulatory cells, and B cells all decrease in aged horses [49,50,51,52,53,54] while CD4:CD8 ratio, a proinflammatory marker, increases in aged equids [51, 52]. The percentage of FOXP3 + CD4 + cells (T-regulatory cells), is also decreased in horses over 15 years of age . T-regulatory cells have an anti-inflammatory role, thus the loss of this cell type with age further drives a proinflammatory phenotype.
While little work has been done in horses examining age-related changes to lymphoid organs such as the thymus, spleen, and lymph nodes, the widespread use of regenerative therapies in equine practice has led to multiple studies comparing stem cell populations in adult and geriatric horses. Studies of equine stem cells derived from bone marrow, adipose, and synovial fluid have demonstrated progressive reductions in cell proliferation and differentiation potential, as well as increased prevalence of age-related binucleate or tetraploid cells. Additionally, stem cells derived from geriatric horses are more likely to show morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy [55,56,57,58].
Although immunosenescence predominantly impairs T cell function, changes in innate immunity occur as well. Innate immunity is considered the first line of defense and includes soluble mediators as well as phagocytic effectors cells such as neutrophils and macrophages. Across species, alternations in neutrophil function associated with increasing age include reductions in phagocytosis, oxidative burst, chemokinesis, and chemotaxis [59,60,61,62]. In contrast, adhesion was found to be greater in neutrophils collected from people 65–80 years old, with increased expression of adhesion molecule CD11b . While most studies have not found a change in neutrophil numbers in the aged [59,60,61,62], Liu and colleagues  reported reduced neutrophil counts and functional alternations in immunity in extremely old female subjects, while Fernandez-Garrido and others  associated neutrophil count increases with frailty. Similarly, age-associated alterations in neutrophil function is associated with increased susceptibility to pseudomonas pneumonia infection in rodents . In this same study, although concentrations of pulmonary chemokines were higher in old mice, neutrophil count in the airways was markedly lower following pseudomonas infection, suggesting a failure in neutrophil chemotaxis with age . In contrast, a study of healthy aged horses found that neutrophil adhesion, oxidative burst, and phagocytosis were all similar to that of healthy adult horses, while chemotaxis was increased in aged horses compared to adult horses . More recently, Miller et al. found that healthy aged horses had reduced concentrations of plasma myeloperoxidase (MPO) (a marker of neutrophil degranulation) when compared to healthy adult horses, with no differences in absolute numbers of segmented and band neutrophils or monocytes to otherwise account for the difference . Differences in study design may explain the contrast in findings. The first study (McFarlane) assessed washed neutrophils stimulated ex vivo while the second (Miller) measured in situ (plasma) products of neutrophil response. The Miller group also reported increased TNFα expression after in vitro stimulation of whole blood with heat-inactivated R. equi in geriatric horses when compared to adult horses . More recently, a study examining the effect of age on equine monocyte function and pro-inflammatory cytokine responses to bacterial lipopolysaccharide (LPS) found that similar to aged people, geriatric horses had reduced monocyte phagocytic capacity as well as increased IL-1β gene expression in response to lipopolysaccharide stimulation [26, 69]. The significance of these changes in innate immunity on disease susceptibility in the aged horse remains unclear.
In contrast to healthy aged horses, current evidence suggests that aged horses with PPID experience impaired neutrophil function and increased frequency of bacterial infection . At this time, early detection of PPID is challenging, and it may therefore be prudent to assume all aged horses are at higher risk for neutrophil impairment until endocrine dysfunction can be definitively ruled out or until more sensitive early disease detection methods are available.
Cytokine and acute phase protein profiles in the aged horse
Serum cytokine profiles in aged people typically favor a pro-inflammatory phenotype [70, 71]. This process is known as inflammaging, and has been postulated to be a contributing mechanism in the process of immunosenescence and development of chronic age-related disease . Aged horses also show similar cytokine profiles with increased gene expression of TNF-α, IL-6, IL-1β IL-8, IFN-γ, IL-15 and IL-18 [19, 52] and increased proinflammatory: anti-inflammatory cytokine ratios including IL6: IL10 and TNF-α:IL10 . When cytokine concentration was examined at the protein rather than gene expression level, the findings were not as clear. Serum cytokine concentration of TNF-α was increased in aged horses in one study  but not another , although both studies were hindered by small sample size. In horses, serum TNF-α concentration can be affected by multiple confounding factors, including concurrent illness, obesity, inflammation and season, any of which could have played role in the contradictory findings in the studies. The role of other serum cytokines in geriatric horses has not been extensively examined.
Less data are available regarding the role of aging on acute phase protein concentration. Zak et al. reported serum amyloid A (SAA), c reactive protein (CRP), haptoglobin, activin A, α-1-antichymotrypsin, and procalcitonin did not differ between healthy adult and aged horses, however, as is common in equine studies, there was an insufficient sample size to draw conclusions without additional work to confirm the finding .
Several studies have evaluated the impact of aging on equine peripheral blood mononuclear cells (PBMC) or whole blood response following ex vivo immune stimulation [19, 52, 53]. In aged primates, stimulation of whole blood or PBMC results in a greater release of proinflammatory cytokines than observed in adults [73,74,75]. Similarly, ex vivo stimulation of equine PBMCs revealed an increase in TNF-α and IFN-γ production with age [19, 52, 53]. This enhanced ex vivo cytokine response may not translate to cytokine response in natural disease, however. A study comparing inflammatory responses in adult and aged horses with naturally occurring intestinal disease found no differences in median concentration of type-2 cytokines IL-4 and IL-10 or type-1 cytokine IFN-γ . Of note, inflammatory cytokines IL-6 and TNF-α were significantly higher in geriatric compared to young-adult horses at all sampling time points, corroborating previous studies suggesting a baseline proinflammatory phenotype in geriatric horses similar to that observed in people [19, 52, 53, 70, 71, 76].
Adaptive immune function
In studies of non-equid species, lymphocyte proliferation has been consistently found to decrease with age. While several mechanisms have been proposed to explain this age-related reduction in proliferation response, including decreases in serum IL-2 concentration and IL-2 receptor expression [35, 77, 78], lymphocyte impairment has also been observed in the absence of these two factors, suggesting that intracellular signaling defects may also be altered with age . Similarly, horses also experience age-associated reductions in lymphocyte proliferation [50, 52]. The decrease in lymphocyte proliferation noted in geriatric horses does not appear to be responsive to IL-2 supplementation, nor does it seem to be associated with altered lymphocyte IL-2 receptor expression , suggesting that in the horse, altered intracellular signaling may be the primary mechanism behind age-related defects in lymphocyte division.
Mechanisms of immunosenescence
Few studies have investigated the underlying mechanisms of immunosenescence in horses. Similar to humans, geriatric horses demonstrate age-associated alterations in leucocyte genomic stability; in one study, aged horses had increases in positive TUNEL cells, oxidative DNA damage, sister chromatid exchange and bleomycin-induced chromatid breaks when compared to non-aged adult horses . Telomere length of leucocytes also decreases with age in horses, although the association between reduced telomere length and reductions in immune function in the elderly equine population have not been as clearly demonstrated as they have in aged people [81, 82]. Mitogen-induced proliferation of PBMCs was also shown to be weakly correlated to relative telomere length, leading the authors to suggest other mechanisms likely have a role in age-related decrease in PBMC proliferation . This study also reported a positive correlation between telomere length and total IgG concentration as well as a negative correlation with inflammatory cytokine expression. Currently evidence that telomere length has a causative role in equine immunosenescence is lacking.
Clinical consequences of immunosenescence in horses
Infectious disease risk
The notion that geriatric horses are at increased risk for infectious diseases is commonly noted throughout the non-scientific equine literature, though there are few controlled studies to support this theory. Recently, trends in morbidity and mortality of aged horses have been investigated through a variety of epidemiological studies utilizing owner surveys, prospective studies with veterinary examinations, and analysis of medical records and pathology reports [83,84,85,86,87]. In all reports, infectious disease was an uncommon cause of disease and death in aged horses. Despite the suggestion that infectious conditions such as strangles (Streptococcus equi equi), influenza, or parasitism are more common in geriatric horses, to the authors’ knowledge, these assertions remain unsubstantiated.
While it appears that geriatric horses may not be broadly more susceptible to infectious disease, there are examples of specific pathogens with a predilection for aged horses. West Nile virus infection may cause more severe disease in geriatric horses compared to adults, as a higher case fatality rate has been reported in aged horses, particularly in previously unexposed animals [88, 89]. Similarly, in horses experimentally challenged with a strain of equine herpesvirus-1 (EHV-1) known to create neurologic disease, aged mares appear more susceptible to develop neurologic signs [90, 91]. In contrast, endoparasite egg shedding in horses does not appear to be affected by age. This observation was based on fecal egg count (FEC) before and after anthelmintic administration (measuring egg reemergence period and total FEC), not by the ideal method of performing worm counts at postmortem . Unlike what is observed in healthy aged horses, two studies reported greater FEC and a shorter egg re-emergence period after anthelmintic treatment in horses with PPID [92, 93], while a group from Switzerland did not find higher FEC in aged horses with “pre-clinical PPID” . Unlike the other 2 studies, they included only horses without clinical signs of PPID. Inclusion into the pre-clinical PPID group was based on ACTH concentration alone.
A key clinical feature of immunosenescence in humans is the progressive decline in antibody response to immunization. A failure to mount protective immunoglobulin concentrations to influenza is observed in the aged population, and contributes to the high morbidity and mortality due to influenza infection in older people [95, 96]. A diminished response of aged horses to influenza vaccination has also been corroborated in multiple studies [95, 97, 98]. Horohov, et al. reported aged ponies displayed a tenfold decrease in titers when compared to non-aged adults . Using a different vaccine, Muirhead, et al. reported that although aged horses developed antibody concentrations considered to be protective, aged horses had lower concentrations of immunoglobulin subtypes IgGa and IgGb . The immune response to influenza vaccination may be further altered in older obese horses and those affected by equine metabolic syndrome (EMS). A study comparing immune response to influenza vaccination in EMS and non-EMS horses resulted in similar humoral responses in both groups, but reduced cell-mediated immunity response in the EMS groups, with influenza-vaccinated EMS horses having lower gene expression of IFN-γ and IL-2 compared to vaccinated non-EMS control horses .
In practice, it is likely important to consider all possible confounders when developing a vaccination strategy for an aged horse, including general health, obesity, and potential endocrine disease. In one study of 200 aged horses, 26% were overweight (body condition score > 3/5) and 22% displayed hirsutism or delayed shedding suggestive of underlying PPID . Despite substantial evidence that aged horses have altered immune response to influenza vaccination, there is a paucity of challenge studies investigating the risk of disease in geriatric horses following standard adult equine vaccination protocols for influenza or other infectious diseases. As a result, specific target titers for protecting aged horses from disease are currently unknown. It is important to note that despite observations of reduced effectiveness of influenza vaccine in aged horses, an increased incidence of naturally occurring influenza infection in older horses has not reported.
Immune response to naïve antigenic challenge has been specifically examined in horses greater than 20 years of age. Differing from what has been reported in other species [102,103,104], the magnitude of a primary antibody response in geriatric horses did not decline with age . Following administration of rabies vaccine to naïve horses, antibody titers after both the first and second immunizations were not different between aged and non-aged adult horses. Of note, however, in this study 80% of the both the control and aged population were found to have low serum selenium concentrations, a potential study confounder. It is unclear if the low selenium may have resulted in a suboptimal vaccine response in both groups. Response to rabies immunization in aged horses was further studied by Harvey and colleagues . They reported that horses > 20 years had a similar magnitude and duration of antibody response to adult horses, with an average duration of a protective titer of 2–3 years. In contrast, naïve horses did not reach protective titers after a single vaccination dose, irrespective of age. Further studies are needed to better characterize the effect of age on naïve and amnestic vaccine challenge and when needed, assist in the development of optimal vaccination protocol for geriatric horses. For the infrequent infectious agents where age appears to be a risk factor for more severe disease (West Nile Virus, EHV-1), of particular interest would be evaluating the use of adjuvants and high antigen dose, similar to those described for improving vaccination response in aged human patients , to improve vaccine efficacy in geriatric horses.
Chronic inflammatory diseases
While aged horses generally maintain an adequate protective immunity against pathogens, the do exhibit a proinflammatory phenotype that may contribute to the high prevalence of inflammatory diseases observed in the geriatric equid. A recent study of 1448 horses greater than 20 years of age found 68.8% were affected with a chronic health condition, with osteoarthritis (42.4%), PPID (26.8%), dental disease (15.1%) and ophthalmic disease (11.1%) the most common conditions reported . The specific mechanisms by which age-associated imbalances in cytokine and acute phase response contribute to the initiation or progression of chronic inflammatory diseases in older horses have not been elucidated, but in humans is postulated to be the result of increased concentrations of circulating proinflammatory mediators produced through chronic inflammatory stimulation, a process termed “inflammaging” [108, 109]. Studies of immune aging in humans have further revealed that oxidative stress has an important role in the development of chronic inflammatory disorders in aged people, likely due to an overall reduction in endogenous antioxidants to counterbalance the production of reactive oxygen species that are generated by many physiological cellular metabolic processes. Asthma, a syndrome of both humans and horses, is characterized by airway hyperresponsiveness, obstruction, mucus hyper-production, and airway wall remodeling, and increases in severity with age in both species. In horses, severe asthma is associated with a dysregulation of innate and acquired immunity resulting in neutrophilic inflammation and an overexpression of Th1, Th2, and/or Th17-type molecules . In horses on pasture (a risk factor for the development of asthma) a significant age-related increase was found in the expression of IL-6, IL-8, TLR-4 and TNF-α in stimulated bronchoalveolar cells and for TNF-α in stimulated PBMCs, suggesting that both age and environment likely contribute to the development of disease .
Immunosenescence may also play an important role in geriatric horses’ ability to recover from inflammatory disorders. One study of horses with naturally-occurring colitis found the likelihood of non-survival increased by 11.8% for every year the horse aged, and that horses ≥ 20 years of age were 15.2 times more likely to die than young adults, independent of financial considerations, comorbidities, and duration of hospitalization . In contrast, a study examining post-operative recovery from colic surgery in aged and adult horses found no differences in the severity of post-operative reflux or likelihood of survival . Clearly much remains to be elucidated regarding the effect of age on disease in horses. A better understanding of the age-related immune dysfunction is needed to facilitate the development of effective preventative strategies to minimize chronic inflammatory diseases in old horses.
The equine population in the United States and worldwide now includes a higher percentage of geriatric horses than ever previously recorded , and as methods to treat and manage elderly equids are developed and refined, this aging population will likely continue to expand. Similar to the aging population of people, much interest exists in maintaining optimal health and function well into late life, and strategies designed to preserve a youthful immune system in the old horse population are needed. In contrast to geriatric humans, healthy aged horses appear to be relatively effective at avoiding infectious diseases. Aged horses, however, do experience a high prevalence of immunosuppressive endocrine disease (eg., PPID), resulting in an increasingly large population of older horses at high risk of impaired immune function. Interventions designed to preserve adaptive immunity and deter the shift towards a proinflammatory bias that occurs in old horses may prevent or delay age-related comorbidities and promote equine health well into old age.
Availability of data and materials
Serum amyloid A
C reactive protein
Peripheral blood mononuclear cells
Pituitary pars intermedia dysfunction
Fecal egg counts
Equine metabolic syndrome
Ireland JL. Demographics, management, preventive health care and disease in aged horses. Vet Clin North Am Equine Pract. 2016;32:195–214. https://doi.org/10.1016/j.cveq.2016.04.001.
McGowan TW, Pinchbeck G, Phillips CJ, Perkins N, Hodgson D, McGowan C. A survey of aged horses in Queensland, Australia. Part 1: management and preventive health care. Aust Vet J. 2010;88:420–7. https://doi.org/10.1111/j.1751-0813.2010.00637.x.
Age-related trends in demographics of equids in United States. In: USDA National Animal Health Monitoring System (NAHMS) Studies. 2015. https://www.aphis.usda.gov/animal_health/nahms/equine/downloads/equine15/Equine15_is_TrendsAge.pdf. Accessed 15 Oct 2022.
Disease burden of influenza. 2022. https://www.cdc.gov/flu/about/burden/index.html. Accessed 15 Nov 2022.
CDC COVID Data Tracker. 2022. https://covid.cdc.gov/covid-data-tracker/#demographicsovertime. Accessed 15 Nov 2022
Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol. 2007;211:144.
McDermott EJ, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, et al. Role of Innate immunity in initiation and progression of osteoarthritis, with emphasis on horses. Animals (Basel). 2021;11:3247.
Hansen S, Otten ND, Fjeldborg J, Baptiste KE, Horohov DW. Age-related dynamics of pro-inflammatory cytokines in equine bronchoalveolar lavage (BAL) fluid and peripheral blood from horses managed on pasture. Exp Gerontol. 2019;124: 110634. https://doi.org/10.1016/j.exger.2019.110634.
Deaths, percent of total deaths, and death rates for the 15 leading causes of death in 10-year age groups, by race and sex: United States, 2015. https://www.cdc.gov/nchs/data/dvs/LCWK2_2015.pdf. Accessed 15 Nov, 2022.
Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, et al. The immune system in extreme longevity. Exp Gerontol. 2008;43:61. https://doi.org/10.1016/j.exger.2007.06.008.
Muylle S, Simoens P, Lauwers H. Ageing horses by an examination of their incisor teeth: an (im)possible task? Vet Record. 1996;138:295–301. https://doi.org/10.1136/vr.138.13.295.
Duan R, Fu Q, Sun Y, Li Q. Epigenetic clock: a promising biomarker and practical tool in aging. Ageing Res Rev. 2022;81: 101743. https://doi.org/10.1016/j.arr.2022.101743.
Larison B, Pinho GM, Haghani A, Zoller JA, Li CZ, Finno CJ, et al. Epigenetic models developed for plains zebras predict age in domestic horses and endangered equids. Commun Biol. 2021;4:1412. https://doi.org/10.1038/s42003-021-02935-z.
Horvath S, Haghani A, Peng S, Hales EN, Zoller JA, Raj K, et al. DNA methylation aging and transcriptomic studies in horses. Nat Commun. 2022;13:40. https://doi.org/10.1038/s41467-021-27754-y.
Wnuk M, Lewinska A, Gurgul A, Zabek T, Potocki L, Oklejewicz B, et al. Changes in DNA methylation patterns and repetitive sequences in blood lymphocytes of aged horses. Age (Dordr). 2014;36(1):31–48. https://doi.org/10.1007/s11357-013-9541-z.
Ligthart GJ, Corberand JX, Geertzen HG, Meinders AE, Knook DL, Hijmans W. Necessity of the assessment of health status in human immunogerontological studies: evaluation of the SENIEUR protocol. Mech Ageing Dev. 1990;55:89–105. https://doi.org/10.1016/0047-6374(90)90108-r.
Zak A, Siwinska N, Elzinga S, Barker VD, Stefaniak T, Schanbacher BJ, et al. Effects of equine metabolic syndrome on inflammation and acute-phase markers in horses. Domest Anim Endocrinol. 2020;72: 106448. https://doi.org/10.1016/j.domaniend.2020.106476.
Siard-Altman MH, Harris PA, Moffett-Krotky AD, Ireland JL, Betancourt A, Barker VD, et al. Relationships of inflamm-aging with circulating nutrient levels, body composition, age, and pituitary pars intermedia dysfunction in a senior horse population. Vet Immunol Immunopathol. 2020;221: 110013. https://doi.org/10.1016/j.vetimm.2020.110013.
McFarlane D, Holbrook TC. Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction. J Vet Intern Med. 2008;22:436–42. https://doi.org/10.1111/j.1939-1676.2008.0076.x.
Holbrook TC, Tipton T, McFarlane D. Neutrophil and cytokine dysregulation in hyperinsulinemic obese horses. Vet Immunol Immunopathol. 2012;145(1–2):283–9. https://doi.org/10.1016/j.vetimm.2011.11.013.
Ligthart GJ, Corberand JX, Fournier C, et al. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev. 1984;28:47–55. https://doi.org/10.1016/0047-6374(84)90152-0.
McGowan TW, Pinchbeck GP, McGowan CM. Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses. Equine Vet J. 2012;45:74–9. https://doi.org/10.1111/j.2042-3306.2012.00578.x.
McFarlane D, Donaldson MT, McDonnell SM, Cribb AE. Effects of season and sample handling on measurement of plasma alpha-melanocyte-stimulating hormone concentrations in horses and ponies. Am J Vet Res. 2004;65:1463–8. https://doi.org/10.2460/ajvr.2004.65.1463.
Donaldson MT, McDonnell SM, Schanbacher BJ, Lamb SV, McFarlane D, Beech J. Variation in plasma adrenocorticotropic hormone concentration and dexamethasone suppression test results with season, age, and sex in healthy ponies and horses. J Vet Intern Med. 2005;19:217–22. https://doi.org/10.1892/0891-6640(2005)19%3c217:vipahc%3e2.0.co;2.
McFarlane D, Paradis MR, Zimmel D, Sykes B, Brorsen BW, Sanchez A, et al. The effect of geographic location, breed, and pituitary dysfunction on seasonal Adrenocorticotropin and α-Melanocyte-stimulating hormone plasma concentrations in horses. J Vet Intern Med. 2011;25:872–81. https://doi.org/10.1111/j.1939-1676.2011.0745.x.
Herbst AC, Reedy SE, Page AE, Horohov DW, Adams AA. Effect of aging on monocyte phagocytic and inflammatory functions, and on the ex vivo inflammatory responses to lipopolysaccharide, in horses. Vet Immunol Immunopathol. 2022;250: 110459. https://doi.org/10.1016/j.vetimm.2022.110459.
Vick MM, Adams AA, Murphy BA, Sessions DR, Horohov DW, Cook RF, et al. Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse. J Anim Sci. 2007;85:1144–55. https://doi.org/10.2527/jas.2006-673.
Adams AA, Katepalli MP, Kohler K, Reedy SE, Stilz JP, Vick MM, et al. Effect of body condition, body weight and adiposity on inflammatory cytokine responses in old horses. Vet Immunol Immunopathol. 2009;127:286–94. https://doi.org/10.1016/j.vetimm.2008.10.323.
Sansoni P, Cossarizza A, Brianti V, Fagnoni F, Snelli G, Monti D, et al. Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood. 1993;82:2767–73.
Greeley EH, Kealy RD, Ballam JM, Lawler DF, Segre M. The influence of age on the canine immune system. Vet Immunol Immunopathol. 1996;55:1–10. https://doi.org/10.1016/s0165-2427(96)05563-8.
Watabe A, Fukumoto S, Komatsu T, Endo Y, Kadosawa T. Alterations of lymphocyte subpopulations in healthy dogs with aging and in dogs with cancer. Vet Immunol Immunopathol. 2011;142:189–200. https://doi.org/10.1016/j.vetimm.2011.05.008.
Maue AC, Yager EJ, Swain SL, Woodland DL, Blackman MA, Haynes L. T-cell immunosenescence: lessons learned from mouse models of aging. Trends Immunol. 2009;30:301–5. https://doi.org/10.1016/j.it.2009.04.007.
Lazuardi L, Jenewein B, Wolf AM, Pfister G, Tzankov A, Grubeck-Loebenstein B. Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology. 2005;114:37–43. https://doi.org/10.1111/j.1365-2567.2004.02006.x.
Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, et al. The influence of age on T cell generation and TCR diversity. J Immunol. 2005;174:7446–52. https://doi.org/10.4049/jimmunol.174.11.7446.
Rea IM, Stewart M, Campbell P, Alexander HD, Crockard AD, Morris TC. Changes in lymphocyte subsets, interleukin 2, and soluble interleukin 2 receptor in old and very old age. Gerontology. 1996;42:69–78. https://doi.org/10.1159/000213775.
Ferrando-Martinez S, Ruiz-Mateos E, Hernandez A, Gutiérrez E, Rodríguez-Méndez Mdel M, Ordoñez A, et al. Age-related deregulation of naive T cell homeostasis in elderly humans. Age (Dordr). 2011;33:197–207. https://doi.org/10.1007/s11357-010-9170-8.
Willis EL, Eberle R, Wolf RF, White GL, McFarlane D. The effects of age and cytomegalovirus on markers of inflammation and lymphocyte populations in captive baboons. PLoS ONE. 2014;9: e107167. https://doi.org/10.1371/journal.pone.0107167.
Pawelec G, Adibzadeh M, Solana R, Beckman I. The T cell in the ageing individual. Mech Ageing Dev. 1997;93:35–45. https://doi.org/10.1016/s0047-6374(96)01812-x.
Lang A, Nikolich-Zugich J. Functional CD8 T cell memory responding to persistent latent infection is maintained for life. J Immunol. 2011;187:3759–68. https://doi.org/10.4049/jimmunol.1100666.
Fulop T, Larbi A, Pawelec G. Human T cell aging and the impact of persistent viral infections. Front Immunol. 2013;4:271. https://doi.org/10.3389/fimmu.2013.00271.
Willis EL, Eberle R, Wolf RF, White GL, McFarlane D. Effects of chronic viral infection on lymphocyte populations in middle-aged baboons (Papio anubis). Comp Med. 2021;71:177–87. https://doi.org/10.30802/AALAS-CM-20-000068.
Pawelec G, Derhovanessian E. Role of CMV in immune senescence. Virus Res. 2011;157:175–9. https://doi.org/10.1016/j.virusres.2010.09.010.
Ouyang Q, Wagner WM, Wikby A, Walter S, Aubert G, Dodi AI, et al. Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old. J Clin Immunol. 2003;23:247–57. https://doi.org/10.1023/a:1024580531705.
Mekker A, Tchang VS, Haeberli L, Oxenius A, Trkola A, Karrer U. Immune senescence: relative contributions of age and cytomegalovirus infection. PLoS Pathog. 2012;8: e1002850. https://doi.org/10.1371/journal.ppat.1002850.
Magden ER, Nehete BP, Chitta S, Williams LE, Simmons JH, Abee CR, et al. Comparative Analysis of Cellular Immune Responses in Conventional and SPF Olive Baboons (Papio anubis). Comp Med. 2020;70:160–9. https://doi.org/10.30802/AALAS-CM-19-000035.
Hodkinson CF, O’Connor JM, Alexander HD, Bradbury I, Bonham MP, Hannigan BM, et al. Whole blood analysis of phagocytosis, apoptosis, cytokine production, and leukocyte subsets in healthy older men and women: the ZENITH study. J Gerontol A Biol Sci Med Sci. 2006;61:907–17. https://doi.org/10.1093/gerona/61.9.907.
Peres A, Bauer M, da Cruz IB, Nardi NB, Chies JA. Immunophenotyping and T-cell proliferative capacity in a healthy aged population. Biogerontology. 2003;4:289–96. https://doi.org/10.1023/a:1026282917406.
Huppert FA, Pinto EM, Morgan K, Brayne C. Survival in a population sample is predicted by proportions of lymphocyte subsets. Mech Ageing Dev. 2003;124:449–51. https://doi.org/10.1016/s0047-6374(03)00021-6.
Ralston SL, Nockels CF, Squires EL. Differences in diagnostic test results and hematologic data between aged and young horses. Am J Vet Res. 1988;49:1387–92.
Horohov DW, Kydd JH, Hannant D. The effect of aging on T cell responses in the horse. Dev Comp Immunol. 2002;26:121–8. https://doi.org/10.1016/s0145-305x(01)00027-1.
McFarlane D, Sellon DC, Gibbs SA. Age-related quantitative alterations in lymphocyte subsets and immunoglobulin isotypes in healthy horses. Am J Vet Res. 2001;62:1413–7. https://doi.org/10.2460/ajvr.2001.62.1413.
Adams AA, Breathnach CC, Katepalli MP, Kohler K, Horohov DW. Advanced age in horses affects divisional history of T cells and inflammatory cytokine production. Mech Ageing Dev. 2008;129:656–64. https://doi.org/10.1016/j.mad.2008.09.004.
Schnabel CL, Steinig P, Schberth HJ, Koy M, Wagner B, Wittig B, et al. Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release. Vet Immuno Immunopath. 2015;165:64–74. https://doi.org/10.1016/j.vetimm.2015.02.011.
Robbin MG, Wagner B, Noronha LE, Antczak DF, de Mestre AM. Subpopulations of equine blood lymphocytes expressing regulatory T cell markers. Vet Immunol Immunopathol. 2011;140:90–101. https://doi.org/10.1016/j.vetimm.2010.11.020.
Mazzotti E, Teti G, Falconi M, Chiarini F, Barboni B, Mazzotti A, et al. Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model. Cells. 2019;8:1116. https://doi.org/10.3390/cells8101116.
Alicka M, Kornicka-Garbowska K, Kucharczyk K, Kępska M, Rӧcken M, Marycz K. Age-dependent impairment of adipose-derived stem cells isolated from horses. Stem Cell Res Ther. 2020;11(1):4. https://doi.org/10.1186/s13287-019-1512-6.
Bagge J, MacLeod JN, Berg LC. Cellular proliferation of equine bone marrow- and adipose tissue-derived mesenchymal stem cells decline with increasing donor age. Front Vet Sci. 2020;7: 602403. https://doi.org/10.3389/fvets.2020.602403.
Bagge J, Berg LC, Janes J, MacLeod JN. Donor age effects on in vitro chondrogenic and osteogenic differentiation performance of equine bone marrow- and adipose tissue-derived mesenchymal stromal cells. BMC Vet Res. 2022;18:388. https://doi.org/10.1186/s12917-022-03475-2.
Schroder AK, Rink L. Neutrophil immunity of the elderly. Mech Ageing Dev. 2003;124:419–25. https://doi.org/10.1016/s0047-6374(03)00017-4.
Peters T, Weiss JM, Sindrilaru A, Wang H, Oreshkova T, Wlaschek M, et al. Reactive oxygen intermediate-induced pathomechanisms contribute to immunosenescence, chronic inflammation and autoimmunity. Mech Ageing Dev. 2009;130:564–87. https://doi.org/10.1016/j.mad.2009.07.003.
Lord JM, Butcher S, Killampali V, Lascelles D, Salmon M. Neutrophil ageing and immunesenescence. Mech Ageing Dev. 2001;122:1521–35. https://doi.org/10.1016/s0047-6374(01)00285-8.
Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol. 2012;24:331–41. https://doi.org/10.1016/j.smim.2012.04.008.
Nogueira-Neto J, Cardoso AS, Monteiro HP, Fonseca FL, Ramos LR, Junqueira VB, et al. Basal neutrophil function in human aging: Implications in endothelial cell adhesion. Cell Biol Int. 2016;40:796–802. https://doi.org/10.1002/cbin.10618.
Liu Z, Wang Y, Huang J, Chu X, Qian D, Wang Z, et al. Blood biomarkers and functional disability among extremely longevous individuals: a population-based study. J Gerontol A Biol Sci Med Sci. 2015;70:623–7. https://doi.org/10.1093/gerona/glu229.
Fernandez-Garrido J, Navarro-Martinez R, Buiques-Gonzalez C, Martínez-Martínez M, Ruiz-Ros V, Cauli O. The value of neutrophil and lymphocyte count in frail older women. Exp Gerontol. 2014;54:35–41. https://doi.org/10.1016/j.exger.2013.11.019.
Chen MM, Palmer JL, Plackett TP, Deburghgraeve CR, Kovacs EJ. Age-related differences in the neutrophil response to pulmonary pseudomonas infection. Exp Gerontol. 2014;54:42–6. https://doi.org/10.1016/j.exger.2013.12.010.
McFarlane D, Hill K, Anton J. Neutrophil function in healthy aged horses and horses with pituitary dysfunction. Vet Immunol immunopath. 2015;165:99–106. https://doi.org/10.1016/j.vetimm.2015.04.006.
Miller AB, Loynachan AT, Barker VD, Adams AA. Investigation of innate immune function in adult and geriatric horses. Vet Immunol Immunopathol. 2021;235: 110207. https://doi.org/10.1016/j.vetimm.2021.110207.
Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL, et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell. 2011;11:867–75. https://doi.org/10.1111/j.1474-9726.2012.00851.x.
Forsey RJ, Thompson JM, Ernerudh J, Hurst TL, Strindhall J, Johansson B, et al. Plasma cytokine profiles in elderly humans. Mech Ageing Dev. 2003;124:487–93. https://doi.org/10.1016/s0047-6374(03)00025-3.
Leng SX, Yang H, Walston JD. Decreased cell proliferation and altered cytokine production in frail older adults. Aging Clin Exp Res. 2004;16:249–52. https://doi.org/10.1007/BF03327392.
De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 2009;15:3003–26. https://doi.org/10.2174/138161209789058110.
Eylar EH, Molina F, Quinones C, Zapata M, Kessler M. Comparison of mitogenic responses of young and old rhesus monkey T cells to lectins and interleukins 2 and 4. Cell Immunol. 1989;121:328–35. https://doi.org/10.1016/0008-8749(89)90031-2.
Gabriel P, Cakman I, Rink L. Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. Exp Gerontol. 2002;37:235. https://doi.org/10.1016/s0531-5565(01)00189-9.
McFarlane D, Wolf RF, McDaniel KA, White GL. Age-associated alteration in innate immune response in captive baboons. J Gerontol A Biol Sci Med Sci. 2011;66:1309–17. https://doi.org/10.1093/gerona/glr146.
Sage SE, Bedenice D, McKinney CA, Long AE, Pacheco A, Wagner B, et al. Assessment of the impact of age and of blood-derived inflammatory markers in horses with colitis. J Vet Emerg Crit Care. 2021;31:779–87. https://doi.org/10.1111/vec.13099.
Chopra RK, Powers DC, Kendig NE, Adler WH, Nagel JE. Soluble interleukin 2 receptors released from mitogen stimulated human peripheral blood lymphocytes bind interleukin 2 and inhibit IL2 dependent cell proliferation. Immunol Invest. 1989;18:961–73. https://doi.org/10.3109/08820138909045783.
Weigle WO. Effects of aging on the immune system. Hosp Pract (Off Ed). 1989;24:112–9. https://doi.org/10.1080/21548331.1989.11703827.
Song L, Kim YH, Chopra RK, Proust JJ, Nagel JE, Nordin AA, et al. Age-related effects in T cell activation and proliferation. Exp Gerontol. 1993;28:313–21. https://doi.org/10.1016/0531-5565(93)90058-l.
Wnuk M, Bugno-Poniewierska M, Lewinska A, Oklejewicz B, Zabek T, Bartosz G, Słota E. Age-related changes in genomic stability of horses. Mech Ageing Dev. 2011;132(5):257–68. https://doi.org/10.1016/j.mad.2011.04.009. (Epub 2011 Apr 30 PMID: 21557962).
Denham J, Stevenson K, Denham MM. Age-associated telomere shortening in Thoroughbred horses. Exp Gerontol. 2019;127: 110718. https://doi.org/10.1016/j.exger.2019.110718.
Katepalli MP, Adams AA, Lear TL, Horohov DW. The effect of age and telomere length on immune function in the horse. Dev Comp Immunol. 2008;32:1409–15. https://doi.org/10.1016/j.dci.2008.06.007.
Silva AG, Furr MO. Diagnoses, clinical pathology findings and treatment outcome of geriatric horses: 345 cases (2006–2010). J Am Vet Med Assoc. 2013;243:1762–8. https://doi.org/10.2460/javma.243.12.1762.
Ireland JL, Clegg PD, McGowan CM, Platt L, Pinchbeck GL. Factors associated with mortality of geriatric horses in the United Kingdom. Prev Vet Med. 2011;101:204–18. https://doi.org/10.1016/j.prevetmed.2011.06.002.
Williams N. Disease conditions in geriatric horses. Equine Disease Quarterly 2000 Vol 8. http://www2.ca.uky.edu/gluck/q/2000/jan00/Q_jan00.htm
McGowan TW, Pinchbeck G, Phillips CJ, Perkins N, Hodgson DR, McGowan CM. A survey of aged horses in Queensland, Australia Part 2: clinical signs and owners’ perceptions of health and welfare. Aust Vet J. 2010;88:465–71. https://doi.org/10.1111/j.1751-0813.2010.00638.x.
Brosnahan MM, Paradis MR. Demographic and clinical characteristics of geriatric horses: 467 cases (1989–1999). J Am Vet Med Assoc. 2003;223:93–8. https://doi.org/10.2460/javma.2003.223.93.
Schuler LA, Khaitsa ML, Dyer NW, Stoltenow CL. Evaluation of an outbreak of West Nile virus infection in horses: 569 cases (2001). J Am Vet Med Assoc. 2004;225:1084–9. https://doi.org/10.2460/javma.2004.225.1084.
Salazer P, Traub-Dargatz JL, Morley PS, Wilmot DD, Steffen DJ, Cunningham WE, et al. Outcome of equids with clinical signs of West Mile virus infection and factors associated with death. J Am Vet Med Assoc. 2004;225:267–74. https://doi.org/10.2460/javma.2004.225.267.
Allen GP. Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses. Am J Vet Res. 2008;69:1595–600. https://doi.org/10.2460/ajvr.69.12.1595.
Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG, Lee Y, et al. Identification of host factors associated with the development of equine herpesvirus myeloencephalopathy by transcriptomic analysis of peripheral blood mononuclear cells from horses. Viruses. 2021;13:356. https://doi.org/10.3390/v13030356.84].
McFarlane D, Hale GM, Johnson EM, Maxwell LK. Fecal egg counts after anthelmintic administration to aged horses and horses with pituitary pars intermedia dysfunction. J Am Vet Med Assoc. 2010;236:330–4. https://doi.org/10.2460/javma.236.3.330.
El-Hage C, Horner A, Preston S, Bamford N, Jabbar A, Hughes K. Faecal egg counts before and after ivermectin treatment in horses with and without pituitary pars intermedia dysfunction. In proceedings: 41st Bain Fallon Memorial Lectures, July 22–25, 2019, Benowa, Queensland, Australia.
Christen G, Gerber V, van der Kolk JH, Frey CF, Fouché N. Fecal strongyle egg counts in horses with suspected pre-clinical pituitary pars intermedia dysfunction before and after treatment with pergolide. Vet J. 2018;235:60–2. https://doi.org/10.1016/j.tvjl.2018.03.007.
Muirhead TL, McClure JT, Wichtel JJ, Stryhn H, Frederick Markham RJ, McFarlane D, et al. The effect of age on serum antibody titers after rabies and influenza vaccination in healthy horses. J Vet Intern Med. 2008;22:654–61. https://doi.org/10.1111/j.1939-1676.2008.0091.x.
Reber AJ, Chirkova T, Kim JH, Cao W, Biber R, Shay DK, et al. Immunosenescence and challenges of vaccination against influenza in the aging population. Aging Dis. 2012;3:68–90.
Adams AA, Sturgill TL, Breathnach CC, Chambers TM, Siger L, Minke JM, et al. Humoral and cell-mediated immune responses of old horses following recombinant canarypox virus vaccination and subsequent challenge infections. Vet Immunol Immunopathol. 2011;139:128–40. https://doi.org/10.1016/j.vetimm.2010.09.006.
Muirhead TL, McClure JT, Wichtel JJ, Stryhn H, Markham RJ, McFarlane D, et al. The effect of age on the immune response of horses to vaccination. J Comp Pathol. 2010;142:S85-90. https://doi.org/10.1016/j.jcpa.2009.10.010.
Horohov DW, Dimock A, Guirnalda P, Folsom RW, McKeever KH, Malinowski K. Effect of exercise on the immune response of young and old horses. Am J Vet Res. 1999;60:643–7.
Elzinga S, Reedy S, Barker VD, Chambers TM, Adams AA. Humoral and cell-mediated immune responses to influenza vaccination in equine metabolic syndrome (EMS) horses. Vet Immunol Immunopathol. 2018;199:32–8. https://doi.org/10.1016/j.vetimm.2018.03.009.
Ireland JL, Clegg PD, McGowan CM, McKane SA, Chandler KJ, Pinchbeck GL. Disease prevalence in geriatric horses in the United Kingdom: veterinary clinical assessment of 200 cases. Equine Vet J. 2012;44:101–6. https://doi.org/10.1111/j.2042-3306.2010.00361.x.
Cicin-Sain L, Smyk-Pearson S, Currier N, Byrd L, Koudelka C, Robinson T, et al. Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates. J Immunol. 2010;184:67396745. https://doi.org/10.4049/jimmunol.0904193.
Smith TP, Kennedy SL, Fleshner M. Influence of age and physical activity on the primary in vivo antibody and T cell-mediated responses in men. J Appl Physiol. 2004;97:491–8. https://doi.org/10.1152/japplphysiol.01404.2003.
Aberle JH, Stiasny K, Kundi M, Heinz FX. Mechanistic insights into the impairment of memory B cells and antibody production in the elderly. Age. 2013;35:371–81. https://doi.org/10.1007/s11357-011-9371-9.
Harvey AM, Watson JL, Brault SA, Edman JM, Moore SM, Kass PH, et al. Duration of serum antibody response to rabies vaccination in horses. J Am Vet Med Assoc. 2016;249:411–8. https://doi.org/10.2460/javma.249.4.411.
Weinberger B. Vaccination of older adults: Influenza, pneumococcal disease, herpes zoster, COVID-19 and beyond. Immun Ageing. 2021;18:38. https://doi.org/10.1186/s12979-021-00249-6.
Ballou ME, Mueller MK, Dowling-Guyer S. Aging equines: understanding the experience of caring for a geriatric horse with a chronic condition. J Equine Vet Sci. 2020;90: 102993. https://doi.org/10.1016/j.jevs.2020.102993.
Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging: an evolutionary perspective on immunosenescence. Ann NY Acad Sci. 2006;908:224–54. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x.
Fulop T, Dupuis G, Witkowski JM, Larbi A. The role of immunosenescence in the development of age-related diseases. Rev Investig Clin. 2016;68:84–91.
Bullone M, Lavoie JP. The contribution of oxidative stress and inflamm-aging in human and equine asthma. Int J Mol Sci. 2017;18:2612. https://doi.org/10.3390/ijms18122612.
Boorman S, Stefanovski D, Southwood LL. Clinical findings associated with development of postoperative reflux and short-term survival after small intestinal surgery in geriatric and mature nongeriatric horses. Vet Surg. 2019;48:795–802. https://doi.org/10.1111/vsu.13217.
Ethics approval and consent to participate
Consent for publication
The authors declare they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
DeNotta, S., McFarlane, D. Immunosenescence and inflammaging in the aged horse. Immun Ageing 20, 2 (2023). https://doi.org/10.1186/s12979-022-00325-5
- Adaptive immunity
- Geriatric horse
- Immune dysfunction
- Innate immunity