Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Quimby, Jessica M.; Erickson, Andrea K.; McLeland, Shannon; Cianciolo, Rachel E.; Maranon, David G.; Lunn, Katharine F.; Elliott, Jonathan; Lawson, Jack; Hess, Ann; Paschall, Rene E; Bailey, Susan M.

doi:10.3390/vetsci8120314

Cited by 3 publications

(4 citation statements)

References 63 publications

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“…7,8,30 Senescence plays a role in aging in the feline kidney, as p16-mediated renal senescence is positively correlated with age in cats without CKD. 31 Taken together with our description of the histologic lesions associated with age, these data present evidence for renal aging in cats, and a concern for decreased ability to withstand injury and promote effective repair.…”

Section: Discussionsupporting

confidence: 56%

Frequency of histologic lesions in the kidneys of cats without kidney disease

Quimby

McLeland

Cianciolo

et al. 2022

Journal of Feline Medicine and Surgery

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Objectives In humans, renal aging is associated with an increased frequency of glomerulosclerosis, interstitial fibrosis, inflammation and tubular atrophy. The purpose of this study was to describe the frequency of renal histopathologic lesions in cats without kidney disease. Methods A cross-sectional study of archival kidney tissue from 74 cats without kidney disease (serum creatinine <1.6 mg/dl; urine specific gravity >1.035) was carried out: 0–4 years (young, n = 18); 5–9 years (mature, n = 16); 10–14 years (senior, n = 34), 15+ years (geriatric, n = 6). Glomerulosclerosis, tubular atrophy, interstitial inflammation and fibrosis, and the presence or absence of lipid in the interstitium and tubules were scored by a pathologist masked to clinical data. Statistical analyses were performed as appropriate. Results Geriatric cats had significantly more glomerulosclerosis than mature ( P = 0.01) and young cats ( P = 0.004). Senior cats had significantly more glomerulosclerosis than young cats ( P = 0.006). Glomerulosclerosis was weakly positively correlated with age ( r = 0.48; P <0.0001). Geriatric cats had significantly more tubular atrophy than mature ( P = 0.02) and young cats ( P <0.0001). Senior cats had significantly more tubular atrophy than young cats ( P <0.0001). Geriatric cats had significantly more inflammation than senior cats ( P = 0.02), mature cats ( P = 0.01) and young cats ( P <0.0001). Senior cats had significantly more inflammation than young cats ( P = 0.004). Geriatric and senior cats had significantly more fibrosis than young cats ( P = 0.01 and P = 0.04, respectively). Frequency of tubular lipid increased with age (young: 28%; mature: 56%; senior: 79%; geriatric: 100%) as did the frequency of interstitial lipid (young: 22%, mature: 56%, senior: 85%, geriatric: 100%). Conclusions and relevance Evidence of renal aging exists in cats. These changes imply that the aging kidney may be more susceptible to injury and impaired healing.

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Section: Discussionsupporting

confidence: 56%

Frequency of histologic lesions in the kidneys of cats without kidney disease

Quimby

McLeland

Cianciolo

et al. 2022

Journal of Feline Medicine and Surgery

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“…Treatments targeting senescent cells and the SASP have broad potential implications in the field of veterinary medicine as the hallmarks of aging ( 6 ) are highly conserved across species ( 227 , 228 ). These hallmarks include DNA damage ( 229 ), telomere shortening ( 230 , 231 ), aberrant proteostasis ( 232 ), epigenetic modifications ( 233 ), altered nutritional signaling ( 234 , 235 ), cell senescence ( 193 , 213 , 215 , 231 , 236 ), stem cell depletion ( 237 ), mitochondrial dysfunction ( 238 , 239 ), and abnormal inflammatory signaling ( 240 , 241 ). Treatment of age-related diseases in veterinary species may further serve to bolster preclinical evidence for use in humans.…”

Section: Discussionmentioning

confidence: 99%

“…Spontaneous chronic kidney disease (CKD) is well-described in cats ( 182 – 185 ). Feline patients suffering from CKD have renal senescence, telomere shortening, and nitrosative stress in renal cells ( 215 ). With similar pathologic findings to humans ( 216 , 217 ), they represent a naturally occurring model for study of senotherapeutics ( 215 ).…”

Section: Senotherapeutic Potential In Veterinary Speciesmentioning

confidence: 99%

“…Feline patients suffering from CKD have renal senescence, telomere shortening, and nitrosative stress in renal cells ( 215 ). With similar pathologic findings to humans ( 216 , 217 ), they represent a naturally occurring model for study of senotherapeutics ( 215 ). In vitro studies utilizing feline renal cells have shown a dose dependent correlation with radiation and SC ( 218 ).…”

Section: Senotherapeutic Potential In Veterinary Speciesmentioning

confidence: 99%

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The potential for senotherapy as a novel approach to extend life quality in veterinary medicine

Williams,

Chow,

Dow

et al. 2024

Front. Vet. Sci.

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Cellular senescence, a condition where cells undergo arrest and can assume an inflammatory phenotype, has been associated with initiation and perpetuation of inflammation driving multiple disease processes in rodent models and humans. Senescent cells secrete inflammatory cytokines, proteins, and matrix metalloproteinases, termed the senescence associated secretory phenotype (SASP), which accelerates the aging processes. In preclinical models, drug interventions termed “senotherapeutics” selectively clear senescent cells and represent a promising strategy to prevent or treat multiple age-related conditions in humans and veterinary species. In this review, we summarize the current available literature describing in vitro evidence for senotheraputic activity, preclinical models of disease, ongoing human clinical trials, and potential clinical applications in veterinary medicine. These promising data to date provide further justification for future studies identifying the most active senotherapeutic combinations, dosages, and routes of administration for use in veterinary medicine.

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Telomere Therapy for Chronic Kidney Disease

et al. 2022

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Chronic kidney disease (CKD) is estimated to affect almost 10% of individuals worldwide and is one of the leading causes of morbidity and mortality. Renal fibrosis, a central pathway in CKD progression (irrespective of etiology), is associated with shortened or dysfunctional telomeres in animal studies. Telomeres are specialized nucleoprotein structures located at the chromosome end that maintain genomic integrity. The mechanisms of associations between telomere length and CKD have not yet been fully elucidated, however, CKD patients with shorter telomere length may have decreased renal function and a higher mortality rate. A plethora of ongoing research has focused on possible therapeutic applications of telomeres with the overall goal to preserve telomere length as a therapy to treat CKD.

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Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Cited by 3 publications

References 63 publications

Frequency of histologic lesions in the kidneys of cats without kidney disease

Frequency of histologic lesions in the kidneys of cats without kidney disease

The potential for senotherapy as a novel approach to extend life quality in veterinary medicine

Telomere Therapy for Chronic Kidney Disease

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