Abstract
Aging results from an accumulation of damage to macromolecules inhibiting cellular replication, repair, and other necessary functions. Damage may be due to environmental stressors such as metal toxicity, oxidative stress caused by imperfections in electron transfer reactions, or other metabolic processes. In an effort to discover medical treatments that counteract this damage, we initiated a search for small molecule drugs from natural sources using life table experiments which, through their unbiased approach, present the opportunity to discover first-in-class molecules. We have identified marine red algae as a source of natural products that slow aging of the invertebrate rotifer Brachionus manjavacas. Rotifers are a promising model organism for life extension studies as they maintain a short, measurable lifespan while also having an extensive literature related to aging. Rotifer lifespan was increased 9-14% by exposure to three of a total of 200 screened red algal extracts. Bioassay guided fractionation led to semi-purified extracts composed primarily of lipids responsible for rotifer life extension. The life extending mixture from the red alga Acanthophora spicifera contained eicosanoic, octadecanoic, and hexadecanoic acids as well as several unidentified unsaturated fatty acids. The life extending effects of these small molecule mixtures are not a result of their direct antioxidant capacity; other unknown mechanisms of action are likely involved. An understanding of how these natural products interact with their molecular targets could lead to selective and effective treatments for slowing aging and reducing age related diseases.