Age-dependent tissue expression patterns of Sirt1 in senescence-accelerated mice

Abstract

Sirtuin 1 (Sirt1) has a range of molecular functions and has emerged as an important protein in aging and metabolic regulations. Studies have reported a correlation between disturbance of Sirt1 activity and the onset of aging‑ or obesity‑associated diseases, including diabetes, cardiovascular disease and neurodegenerative disorders. However, a systematic investigation to examine the changes of Sirt1 expression in a wide range of ages and to what degree it changes has yet to be performed. To assess the effects of aging on the changes of Sirt1 expression, an in vivo model of aging, senescence-accelerated mouse prone 8 (SAM‑P8) and a control counterpart strain, senescence-accelerated mouse resistant 1 (SAM‑R1) was used. The mRNA and protein expression levels of Sirt1 were detected in four different tissues, including brain, liver, skeletal muscle and white adipose tissue, in both strains at different ages (1-, 4-, 8- and 12-month old). Therefore, different life stages, including young age prior to maturation, adult, middle age and old age were examined. The results identified that Sirt1 expression declined with age at the transcriptional and translational levels in the brain, liver, skeletal muscle and white adipose tissue in SAM-P8 and SAM‑R1. The Sirt1 expression level was lower in SAM-P8 than in SAM‑R1, particularly at old age. Among the four tissues, it was most significantly reduced in the brain.

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

“…This analysis revealed that SIRT1 decreases sharply from birth to young adulthood, and levels continue to decline as mice transition into old age (Figure 1a,b). These findings are consistent with observations that SIRT1 declines in brain, liver, muscle, heart, and adipose tissue during aging (Gong et al, 2014; Sakamoto et al, 2004). These results raise the possibility that SIRT1 may be similarly dysregulated in ALS, a disease that alters fat metabolism and causes muscle wasting and motor neuron loss.…”

“…Through these actions, SIRT1 functions to maintain cellular homeostasis and thereby prevent age‐related pathological changes. Unfortunately, the activity of SIRT1 decreases with advancing age in many cells and tissues either due to a decrease in protein levels (Gong et al, 2014; Sakamoto, Miura, Shimamoto, & Horio, 2004), a reduction in NAD+levels (Imai & Guarente, 2014) or both.…”

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

“…Of importance, key processes of adipose tissue physiology affect molecular pathways that regulate lifespan [18]. For example, SIRT1 levels decline with age in several tissues, including adipose tissue, and this reduction is acerbated in a mouse model of accelerated aging contributing to aging-induced obesity, impaired browning, and the development of metabolic syndrome [19]. Another key regulator in aging is signalling of the serine/threonine protein kinase mTOR.…”

The influence of rs2273773 and rs7895833 SIRT1 gene polymorphisms on life expectancy in context of metabolic factors in Silesian population

“…Sirtuins are produced both by the simplest singlecelled forms of life and by mammals, including the human body [10]. They are expressed in many tissues, including the brain, myocardium, kidney, liver, vascular endothelium and white adipose tissue [11]. The clinical effects of sirtuins, which have been observed in many studies conducted in various organisms, depended on their activity.…”

“…Do ich ekspresji dochodzi w wielu tkankach m.in. w mózgu, mięśniu sercowym, nerkach, wątrobie, śródbłonku naczyniowym czy białej tkance tłuszczowej [11]. W wielu badaniach na różnych organizmach zaobserwowano kliniczny efekt ich działania zależny od ich aktywności.…”