Plant and fungal products that extend lifespan in Caenorhabditis elegans

Abstract

The nematode Caenorhabditis elegans is a useful model to study aging due to its short lifespan, ease of manipulation, and available genetic tools. Several molecules and extracts derived from plants and fungi extend the lifespan of C. elegans by modulating aging-related pathways that are conserved in more complex organisms. Modulation of aging pathways leads to activation of autophagy, mitochondrial biogenesis and expression of antioxidant and detoxifying enzymes in a manner similar to caloric restriction. Low and moderate concentrations of plant and fungal molecules usually extend lifespan, while high concentrations are detrimental, consistent with a lifespan-modulating mechanism involving hormesis. We review here molecules and extracts derived from plants and fungi that extend the lifespan of C. elegans, and explore the possibility that these natural substances may produce health benefits in humans.

Keywords: autophagy; caloric restriction mimetics; dietary supplements; hormesis; phytochemicals.

Figure 1. FIGURE 1: Images of C. elegans nematode used as a model to study aging and longevity.

(A) Light microscopy and (B) fluorescence microscopy images of transgenic C. elegans strain CGUIS-1 expressing the nucleolar protein fibrillarin 1 (FIB-1) coupled to green fluorescent protein (GFP). FIB-1 is a marker of nucleolus size that negatively correlates with longevity across taxa [161], making the CGUIS-1 strain useful for screening natural products that may extend lifespan. In B, GFP auto-fluorescence is induced by ultraviolet light. The images are unpublished observations made by the authors.

Figure 2. FIGURE 2: Aging-related pathways modulated by plant and fungal molecules in C. elegans.

Plant and fungal molecules extend nematode lifespan by inducing the formation of ROS, by activating AAK-2/AMPK, or by inhibiting the insulin or TOR pathway. General cellular pathways are shown here, but variations may occur between cells of different tissues. Human protein homologs are given in green. Abbreviations: AGE-1, phosphatidylinositol 3-kinase age 1; AMP, adenosine monophosphate; ATP, adenosine triphosphate; AAK-2, 5' adenosine-monophosphate-activated protein kinase catalytic subunit alpha 2; AMPK, 5' adenosine-monophosphate-activated protein kinase; CAT, catalase; DAF, abnormal dauer formation protein; FOX, forkhead box; HLH-30, basic helix-loop-helix protein 30; HSF-1, heat-shock factor 1; HSPs, heat-shock proteins; IGF-1, insulin-like growth factor 1; IGF-1R, insulin-like growth factor 1 receptor; IR, insulin receptor; JNK, c-Jun N-terminal kinase; mTOR, mammalian target of rapamycin; Nrf, nuclear factor erythroid 2-related factor; PDK-1, 3' phosphoinositide-dependent protein kinase 1; PHA-4, defective pharyngeal development protein 4; PI3K, phosphoinositide 3-kinase; ROS, reactive oxygen species; SGK-1, serum and glucocorticoid-regulated kinase-1; Sir-2.1, sirtuin 2.1; SIRT-1, sirtuin 1; SKN-1, skinhead 1; SOD, superoxide dismutase; TFEB, HLH transcription factor EB; TOR, target of rapamycin.