Distinct signatures on d‐galactose‐induced aging and preventive/protective potency of two low‐dose vitamin D supplementation regimens on working memory, muscular damage, cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation

Abstract

Chronic administration of d‐galactose (d‐gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d‐gal‐induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre‐induction and simultaneous, respectively) in two vital organs (heart and brain). d‐gal‐induced notorious alterations in working memory, a strong increase in brain malondialdehyde (MDA) oxidative levels, and strong downregulation of sirtuin 1 (SIRT1) in the heart and hippocampus and of calstabin2 in the heart. Cardiac and brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic antioxidant capacities were damaged, brain calstabin2 was downregulated, and neuropathology was observed. Heart damage also included a moderate increase in MDA levels, serologic lactate dehydrogenase (LDH), total creatine kinase (CK) activities, and histopathological alterations. The used dose of vitamin D was enough to prevent cognitive impairment, avoid muscular damage, hamper cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation. Most importantly, the potencies of the two preventive schedules depended on the tissue and level of study. The pre‐induction schedule prevented d‐gal‐induced aging by 1 order of magnitude higher than simultaneous administration in all the variables studied except for SIRT1, whose strong downregulation induced by d‐gal was equally prevented by both schedules. The benefits of vitamin D for oxidative stress were stronger in the brain than in the heart. Brain MDA levels were more sensitive to damage, while SOD and GPx antioxidant enzymatic activities were in the heart. In this order, the magnitude of SOD, MDA, and GPx oxidative stress markers was sensitive to prevention. In summary, the results unveiled distinct aging induction, preventive signatures, and sensitivity of markers depending on different levels of study and tissues, which are relevant from a mechanistic view and in the design of targeted interventions.

Resveratrol prevents age‐related heart impairment through inhibiting the Notch/NF‐κB pathway

“…Cardiovascular disease (CVD) represents a major complication of aging and is recognized as the main cause of mortality among elderly individuals. The oxidative stress theory is currently considered the most reasonable mechanism of aging related‐damage (Salemi et al., 2023 ). The excessive production of reactive oxygen species (ROS) could result in oxidative stress and pro‐inflammatory responses, causing protein oxidation, lipid peroxidation, and DNA damage.…”

“…

Aging is a complex process of degeneration that increases the risk of various chronic diseases (Kazemi Pordanjani et al, 2023).Cardiovascular disease (CVD) represents a major complication of aging and is recognized as the main cause of mortality among elderly individuals. The oxidative stress theory is currently considered the most reasonable mechanism of aging related-damage (Salemi et al, 2023). The excessive production of reactive oxygen species (ROS) could result in oxidative stress and pro-inflammatory

…”