Sirtuins, a promising target in slowing down the ageing process

Abstract

Ageing is a plastic process and can be successfully modulated by some biomedical approaches or pharmaceutics. In this manner it is possible to delay or even prevent some age-related pathologies. There are some defined interventions, which give promising results in animal models or even in human studies, resulting in lifespan elongation or healthspan improvement. One of the most promising targets for anti-ageing approaches are proteins belonging to the sirtuin family. Sirtuins were originally discovered as transcription repressors in yeast, however, nowadays they are known to occur in bacteria and eukaryotes (including mammals). In humans the family consists of seven members (SIRT1-7) that possess either mono-ADP ribosyltransferase or deacetylase activity. It is believed that sirtuins play key role during cell response to a variety of stresses, such as oxidative or genotoxic stress and are crucial for cell metabolism. Although some data put in question direct involvement of sirtuins in extending human lifespan, it was documented that proper lifestyle including physical activity and diet can influence healthspan via increasing the level of sirtuins. The search for an activator of sirtuins is one of the most extensive and robust topic of research. Some hopes are put on natural compounds, including curcumin. In this review we summarize the involvement and usefulness of sirtuins in anti-ageing interventions and discuss the potential role of curcumin in sirtuins regulation.

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

“…Because of the essential role of the NAD + /sirtuin pathway in the metabolic regulation of aging (Grabowska, Sikora & Bielak‐Zmijewska, 2017), we hypothesized that the overexpression of NQO1 and CYB5R3, two NAD + ‐producing enzymes, may affect either NAD + metabolism, sirtuin expression and/or activity, or both. As expected, NAD + and NADP + levels were significantly higher in RedTg vs. Wt muscle (Figure 4a), accompanied by an accumulation of SIRT1 protein and a trend toward lower total lysine‐acetylated protein levels in RedTg muscle (Figure 4b,c).…”

Sirtuins and Accelerated Aging in Scleroderma

“…Sirtuins are considered among the most promising targets for modulating aging-associated cellular and molecular processes and disease pathologies [41]. They have been shown to promote longevity in species across multiple taxonomic groups in response to caloric restriction or activation with molecules such as resveratrol [35, 42–47].…”

“…They have been shown to promote longevity in species across multiple taxonomic groups in response to caloric restriction or activation with molecules such as resveratrol [35, 42–47]. Multiple studies have shown declines in SIRT activity or levels with age in different organisms, tissues, and cells types [41, 48–52]. SIRT6 and SIRT7 knockout mice display progeroid phenotypes and have shorter lifespans than controls [53, 54], and SIRT3 polymorphisms have been associated with longevity in human populations [55].…”

A potential role for the silent information regulator 2 homologue 1 (SIRT1) in periapical periodontitis

“…SIRT1 exhibits a variety of functions in many organisms. The enzyme exerts anti-ageing actions and is involved in calorie restriction, DNA repair and inhibition of inflammation (Baur et al 2006, Zhang et al 2010, Grabowska et al 2017.…”