Newly discovered compounds make age regulating enzyme more responsive to NAD+

Researchers have uncovered compounds that boost the activity of Sirtuin-3 (SIRT3) – an important age-regulating enzyme which was previously thought to be impossible to target with drugs.

SIRT3 keep our mitochondria – known as the cell’s energy factories – working properly. According to researchers, the newly discovered compounds work by making SIRT3 more responsive to NAD+, a molecule that naturally declines as we age and is linked to many age-related illnesses.

The researchers say the compounds restore the enzyme’s activity to more “youthful” levels and could hold potential for clinical development to address a range of disorders such as Alzheimer’s, Parkinson’s, cardiovascular conditions, and metabolic diseases.

For the study, the researchers from developer of the compounds, CCM Biosciences, applied computational and experimental design techniques to identify compounds that drastically enhance SIRT3’s activity.

Previously, SIRT3 has been considered undruggable due to the absence of a known allosteric – or ‘regulatory’ – site.

CCM has said that the compounds fully restored SIRT3 activity under NAD+ depletion conditions mimicking old age, with NAD+ levels reduced by half.

The scientists demonstrated this effect across multiple cell lines used in ageing studies, and the compounds are now undergoing animal testing in mice for age-related disorders, including infertility, where CMM says they have outperformed both NAD+ supplements and existing sirtuin activators.

“Our compounds restore SIRT3 function to youthful levels and offer a novel approach to addressing the molecular hallmarks of ageing,” said Dr. Thomas Delacroix, a senior author involved in the study.

Dr. Michael Pollak at McGill University and an expert on clinical trials for age-related disorders said:

“The discoveries by CCM Biosciences pertaining to the design of drug candidates that can activate the major mitochondrial pathways regulated by sirtuins, along with the clinical development plan for evaluation of efficacy as well as safety of these drug candidates, revitalise this area of drug development.”