The present invention relates to regulation of adult lifespan in
eukaryotes. More particularly, the present invention is directed to
methods of assaying for genes, gene products, and genes in pathways
controlled by such genes and gene products, using RNAi and microarray
analysis, that regulate lifespan (e.g., extend or truncate adult
lifespan) in eukaryotes such as invertebrates (e.g., C. elegans), plants,
and mammals, e.g., humans. For example, the present invention is directed
to genes encoding components of the mitochondrial respiratory chain and
genes encoding glycolysis enzymes, which are involved in lifespan
regulation, and genes and gene products in pathways controlled by such
genes. Other genes and gene products identified as regulating aging and
aging pathways include a gene encoding a GTPase; a transcriptional
activator; novel genes: llw-1, llw-2, llw-3, and llw-4; genes encoding
cytochrome P450 proteins (involved in steroid biosynthesis); a melatonin
synthesis gene; genes encoding insulin and insulin-like peptides; genes
encoding heat shock factors; genes encoding catalases; stress-response
genes; and metabolic genes. The invention further relates to methods for
identifying and using agents, including small molecule chemical
compositions, antibodies, antisense nucleic acids, and ribozymes, that
regulate, e.g., enhance, adult lifespan via modulation of aging
associated proteins; as well as to the use of expression profiles,
markers, and compositions in diagnosis and therapy related to lifespan
extension, life expectancy, and aging. The present invention also relates
to gene therapy involving lifespan associated genes.