Ageing is a stochastic process associated with a progressive decline in physiological functions which predispose to the pathogenesis of several
neurodegenerative diseases. The intrinsic complexity of ageing remains a significant challenge to understand the cause of this natural phenomenon. At the molecular level, ageing is thought to be characterized by the accumulation of chronic oxidative damage to
lipids,
proteins and
nucleic acids caused by
free radicals. Increased oxidative stress and misfolded
protein formations, combined with impaired compensatory mechanisms, may promote
neurodegenerative disorders with age. Nutritional modulation through calorie restriction has been shown to be effective as an anti-ageing factor, promoting longevity and protecting against neurodegenerative pathology in yeast, nematodes and murine models. Calorie restriction increases the intracellular levels of the essential
pyridine nucleotide,
nicotinamide adenine dinucleotide (
NAD(+)), a co-substrate for the
sirtuin 1 (
Sirt1, silent mating-type information regulator 2 homolog 1) activity and a cofactor for oxidative phosphorylation and
ATP synthesis. Promotion of intracellular
NAD(+) anabolism is speculated to induce
neuroprotective effects against
amyloid-β-
peptide (Aβ) toxicity in some models for
Alzheimer's disease (AD). The
NAD(+)-dependent
histone deacetylase,
Sirt1, has been implicated in the ageing process.
Sirt1 serves as a deacetylase for numerous
proteins involved in several cellular pathways, including stress response and apoptosis, and plays a protective role in
neurodegenerative disorders, such as AD.