Sirtuin (SIRT1 -SIRT7) are a group of enzymes with varying intracellular location that either function as histone deacetylase or as mono-ribosyltransferase. Sirtuins are classified according to intracellular location and enzymatic activities and function. SIRT1, 2, 3. 6 are deacetylase and SIRT4, 6 are ADP-ribosyl transferase.

Sirtuins are involved in a diverse biological functions including cell development, metabolism, gene silencing, DNA repair, cell cycle progression, apoptosis, heterochromatin formation and especially longevity. Sirtuins regulates transcription, apoptosis and energy efficiency especially in response to stress and calorie restriction. Sirtuins regulates the activity of the many genes that are responsible for the metabolism, cell defense, reproduction and other bodily functions. Sirtuins are known to play a role in the aging process and life extension. The role of Sirtuins in aging is based on the fact that:

1) Sirtuins with histone deacetylase activity mediate the histone acetylation/deacetylation modification of DNA which in turn either switch on or off the genes during aging process. Histone deacetylation (gene silencing) pattern have been known to be associated with the programmed mechanism of aging. Sirtuins are NAD dependent enzymes that the acetylation/deacetylation reaction require NADH hydrolysis. The dependence of sirtuins on NAD links their enzymatic activity directly to the energy status of the cell via the cellular NAD:NADH ratio. Mitochondria Sirtuins with deacetylase activities may be associated with cellular energy regulation.

2) Sirtuins with mono-ADP-ribosyltransferase activity mediate DNA repair function. Body’s internal DNA repair mechanism is an indispensable component of the protective mechanisms that functions to repair DNA damages (DNA mutation) induced by external stressor such as free radical (oxidative stress) and UV radiation and other mutagens. This process provide a protective mechanism for slowing down the aging process.

The pattern and the level of sirtuins from skin samples with varying age were studied and compared. Comparative studies of skin samples aged 30 to 55 did not reveal any significant age-related difference in SIRT1 level without external stimuli. Sirtuins levels are increased, however, upon UVB irradiation in a dose dependent pattern suggesting the anti-aging role of sirtuins in response to stress induced aging process. With aging, the extent of the increase of sirtuin proteins in response to stress is decreased, indicating that this adaptive anti-aging function to stress is less effective in aged skin cells. The addition of STAC (selective sirtuin activating compound) to the aged skin cell samples in vitro restores this adaptive ability which result in extension of the lifespan of the aged skin cells.

Sirtuins can be the anti-aging enzyme to be targeted on in the skin care industry. Sirtuins may prolong the life of the fibroblasts – the cell synthesize important skin proteins collagen and elastin and other ECM components – of skin. Various studies i vitro and ex vivo using sirtuins stimulators (resveratrol or other sirtuin activator) has revealed that the significant increase of SIRT1 level in normal human dermal skin fibroblasts in vitro (+172%) and in epidermal cells of healthy human skin ex vivo induced by SIRT1 activator can result in decreased cell senescence and DNA fragmentation induced by ultraviolet-B (UVB) stress. In vivo studies indicate that facial improvements could be seen on fine lines and wrinkle, complexion radiance, firmness, complexion homogeneity, and texture was significant immediately after the first application of SIRT1 activator.

One of the most effective known methods of life extension proposed is caloric restriction which works in part by increasing the activity of sirtuins. The calorie restriction approach emphasize a diet strategy with low calorie intake without compromising the essential nutrients such as vitamins and others etc. The theory that caloric restriction may extend life span is base on the fact that the mitochondria energy metabolism is accompanied with byproduct free radicals (ROS, the reactive oxygen species) which can damage cells and biomacromolecules. Through suppressing the energy metabolism to an appropriate level, the effect of free radical damage may be minimized. Sirtuins are the class of enzymes that are induced and increased in response to caloric restriction.

The fact that Sirtuins are partially responsible for the life span and effects on health of caloric restriction has lead to the search for ingredients that will stimulate sirtuin activity in the body. An effective sirtuin activator is resveratrol – an anti-aging ingredients in topical skin care products and other life extension products. Sirtuins, found in Pro-SirtuinSX in Avon Anew Ultimate Age Repair Elixir Serum and Night Cream, prolong the life of the fibroblasts by turning off unnecessary gene expression (i.e., when the fibroblasts aren’t expending more energy than they need to on unnecessary tasks, they will last longer). There are companies that are claiming to produce creams that contain sirtuins instead of sirtuins stimulators, this would presumably by-pass the need for a sirtuin activator. However sirtuins are fairly unstable and a large protein that may not be effective if the ingredient can not be absorbed into the dermis layer of the skin efficiently, the same issue as using collagen as the ingredient instead of collagen stimulators.