The aging feline kidney: A model mortality antagonist?

Abstract

Traditional thinking views apparently non-programmed disruptions of aging, which medical science calls geriatric diseases, as separate from 'less harmful' morphological and physiological aging phenotypes that are more universally expected with passage of time (loss of skin elasticity, graying of hair coat, weight gain, increased sleep time, behavioral changes, etc). Late-life disease phenotypes, especially those involving chronic processes, frequently are complex and very energy-expensive. A non-programmed process of homeostatic disruption leading into a death trajectory seems inconsistent with energy intensive processes. That is, evolutionary mechanisms do not favor complex and prolonged energy investment in death. Taking a different view, the naturally occurring feline (Felis silvestris catus) renal model suggests that at least some diseases of late life represent only the point of failure in essentially survival-driven adaptive processes. In the feline renal model, individuals that succumbed to failure most frequently displayed progressive tubular deletion and peritubular interstitial fibrosis, but had longer mean life span than cats that died from other causes. Additionally, among cats that died from non-renal causes, those that had degrees of renal tubular deletion and peritubular interstitial fibrosis also had longer mean life span than those cats with no changes, even though causes of death differed minimally between these latter two groups. The data indicate that selective tubular deletion very frequently begins early in adult life, without a clear initiating phase or event. The observations support a hypothesis that this prolonged process may be intrinsic and protective prior to an ultimate point of failure. Moreover, given the genetic complexity and the interplay with associated risk factors, existing data also do not support the ideas that these changes are simple compensatory responses and that breed- or strain-based 'default' diseases are inevitable results of increasing individual longevity. Emerging molecular technology offers the future potential to further evaluate and refine these observations. At present, the existence of plastic and adaptive aging programming is suggested by these findings.

Histomorphometry of Feline Chronic Kidney Disease and Correlation With Markers of Renal Dysfunction

“…Notably, the cats with specific renal diseases in this study were younger at death than the cats with nonspecific renal lesions. Previous studies have also found cats with nonspecific renal lesions to be older, 15,19 suggesting these lesions might represent a disease process that progresses more slowly. Chronic inflammation is often implicated in the development of fibrosis via mechanisms such as macrophage activation, so the correlation between interstitial inflammation and fibrosis scores is noteworthy.…”

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

“…An association between age and survival time is not a novel finding,31 and makes sense biologically. Aging is associated with a decreased ability to repair and regenerate the kidney32 and renal histopathologic changes are observed with increasing frequency in older cats 33. Aged rodent kidneys develop significantly more interstitial fibrosis post‐reperfusion than young kidneys, despite normal aged kidneys having no interstitial fibrosis 34.…”

Evaluation of Predictors of the Development of Azotemia in Cats

“…The prevalence of CKD in cats has been reported to increase with advancing age and in human adults age is a factor significantly associated with the development of CKD. 1,15 Recently, a study by Lawler et al 45 suggested that feline CKD may be part of a normal aging phenomenon and a survival driven adaptive process. In that study, cats that died of renal causes displayed progressive tubular deletion and interstitial fibrosis and were significantly older than cats that died from nonrenal causes.…”