Purpose: Aging is accompanied by a chronic low-grade systemic inflammatory state known as “inflammaging”, driven by the accumulation of pro-inflammatory and immunosenescent cells, oxidative stress, and dysregulation of apoptosis and autophagy. Experimental evidence suggests that caloric restriction (CR) can slow down inflammaging, although its impact on spermatogenesis remains controversial. This study aimed to investigate the effects of CR on age-related testicular inflammation and any effects on germ cells. Methods: Fourteen 18-month-old Sprague-Dawley rats were randomly divided into two groups and sacrificed after 6 months: 7 rats on a normal ad libitum diet (ND) and 7 rats on CR (40% reduction in caloric intake). Western blot (WB) and immunohistochemical (IHC) analyses were performed to assess the expression of key markers of inflammation, oxidative stress, apoptosis, and autophagy, alongside morphological evaluations. Results: IHC analysis reveals that CR disrupts germinative epithelium and somatic cells, and reduces the expression of Ob-R, GLP-1R, GPX4, NOX4, and SIRT1. WB analysis showed that CR lowered COX2 expression, through downregulation of the NFκB/MAPK pathway, decreased the expression of NLRP3 inflammasome, Caspase-1, and pro-inflammatory cytokine IL1-β, and restored redox homeostasis. Consistently, IHC highlighted a marked reduction in proinflammatory immune cell infiltration in the testis of CR rats. Moreover, as a consequence of the germ cells number reduction CR-induced, we observed a decreased expression of p75NTR and its pro-apoptotic signaling components (pJNK, p53, and BAX), while concurrently downregulating p62/SQSTM1 expression. Conclusions: Our findings highlight the dual impact of CR on testicular aging, on the one hand the significant attenuation of oxi-inflammation, on the other hand the impairment of germinal epithelial physiology. These results underscore the need for further studies to define optimal timing and duration of dietary interventions aimed at mitigating age-related decline in male reproductive function.
Caloric restriction attenuates oxidative and inflammatory markers of aging, while compromising germinative epithelium homeostasis in the rat aged testis
Bossio S.;Aversa A.;Di Agostino S.;
2026-01-01
Abstract
Purpose: Aging is accompanied by a chronic low-grade systemic inflammatory state known as “inflammaging”, driven by the accumulation of pro-inflammatory and immunosenescent cells, oxidative stress, and dysregulation of apoptosis and autophagy. Experimental evidence suggests that caloric restriction (CR) can slow down inflammaging, although its impact on spermatogenesis remains controversial. This study aimed to investigate the effects of CR on age-related testicular inflammation and any effects on germ cells. Methods: Fourteen 18-month-old Sprague-Dawley rats were randomly divided into two groups and sacrificed after 6 months: 7 rats on a normal ad libitum diet (ND) and 7 rats on CR (40% reduction in caloric intake). Western blot (WB) and immunohistochemical (IHC) analyses were performed to assess the expression of key markers of inflammation, oxidative stress, apoptosis, and autophagy, alongside morphological evaluations. Results: IHC analysis reveals that CR disrupts germinative epithelium and somatic cells, and reduces the expression of Ob-R, GLP-1R, GPX4, NOX4, and SIRT1. WB analysis showed that CR lowered COX2 expression, through downregulation of the NFκB/MAPK pathway, decreased the expression of NLRP3 inflammasome, Caspase-1, and pro-inflammatory cytokine IL1-β, and restored redox homeostasis. Consistently, IHC highlighted a marked reduction in proinflammatory immune cell infiltration in the testis of CR rats. Moreover, as a consequence of the germ cells number reduction CR-induced, we observed a decreased expression of p75NTR and its pro-apoptotic signaling components (pJNK, p53, and BAX), while concurrently downregulating p62/SQSTM1 expression. Conclusions: Our findings highlight the dual impact of CR on testicular aging, on the one hand the significant attenuation of oxi-inflammation, on the other hand the impairment of germinal epithelial physiology. These results underscore the need for further studies to define optimal timing and duration of dietary interventions aimed at mitigating age-related decline in male reproductive function.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
