Methods of screening and compositions for life span modulators

A method of screening for a bioactive agent capable of binding to a chronological life span extension protein, wherein the chronological life span protein is encoded by a nucleic acid encoding a gene as set forth in Table 1 or ortholog thereof, or fragment thereof, the method comprising:

• a) combining the chronological life span protein and a candidate bioactive agent;
• and b) determining the binding of the bioactive agent to the life span protein.

A method for screening for a bioactive agent capable of modulating the activity of a chronological life span protein, wherein the chronological life span protein is encoded by a nucleic acid encoding a gene as set forth in Table 1 or ortholog thereof, or fragment thereof, the method comprising:

• a) combining the chronological life span protein and a candidate bioactive agent;
• and b) determining the effect of the bioactive agent on the bioactivity of the chronological life span protein.

A method of evaluating the effect of a chronological life span modulating drug comprising:

• a) administering the drug to a mammal;
• b) removing a cell sample from the mammal;
• and c) determining the expression of a gene set forth in Table 1 or ortholog thereof.

A method of diagnosing a chronological life span disease or related disorder comprising:

• a) determining the expression of one or more genes set forth in Table 1 or ortholog thereof, or a polypeptide encoded thereby in a first tissue type or cell of a first subject;
• and b) comparing the expression of the gene(s) from a second normal tissue type or cell from the first subject or a second unaffected subject;
• wherein a difference in the expression indicates that the first subject has a chronological life span or related disorder.

A method for screening for a bioactive agent capable of interfering with the binding of a chronological life span protein or a fragment thereof and an antibody which binds to the chronological life span protein or fragment thereof, the method comprising:

• a) combining a chronological life span or fragment thereof, a candidate bioactive agent and an antibody which binds to the chronological life span extension protein or fragment thereof;
• and b) determining the binding of the chronological life span extension protein or fragment thereof and the antibody.

A method for inhibiting the activity of a chronological life span protein, wherein the chronological life span protein is a gene product of a gene set forth in Table 1 or ortholog thereof, or a fragment thereof, the method comprising binding an inhibitor to the chronological life span protein.

A method of treating a chronological life span disease, disorder or related disease or disorder comprising administering to a subject an inhibitor of a chronological life span protein, wherein the chronological life span protein is a gene product of a gene set forth Table 1 or ortholog thereof, or a fragment thereof.

A method of neutralizing the effect of a chronological life span protein, or a functional fragment thereof, comprising contacting an agent specific for the protein, or a functional fragment thereof, with the protein in an amount sufficient to effect neutralization.

A method of treating a chronological life span disease, disorder or related disease or disorder in a subject comprising administering to the subject a nucleic acid molecule that hybridizes under stringent conditions to a target gene as shown in Table 1 or ortholog thereof, or fragment thereof, and attenuates expression of the target gene.

A method of inhibiting expression of a gene or its ortholog as shown in Table 1 comprising the steps of (i) providing a biological system in which expression of a gene shown in Table 1 or ortholog thereof to be inhibited;

• and (ii) contacting the system with a double stranded RNA molecule that hybridizes to a transcript encoding the protein translated from the gene;
• and (iii) inhibiting expression of the gene encoding the protein.

A compound comprising a double stranded RNA having a nucleotide sequence that hybridizes under stringent conditions to a target gene shown in Table 1 or an ortholog thereof, and attenuates expression of said target gene.

A compound that inhibits a chronological life span gene, the compound comprising an oligonucleotide that interacts with an ortholog of a gene shown in Table 1 having at least about 40% sequence similarity to the ortholog.

A biochip comprising one or more nucleic acid segments encoding the genes as shown in Table 1 or ortholog thereof, or a fragment thereof, wherein the biochip comprises fewer than 1000 nucleic acid probes.

A method for treating a chronological life span extension disease, disorder susceptibility or related disease or disorder susceptibility comprising:

• providing a subject at risk of or suffering from a chronological life span disease, disorder or related disease or disorder;
• and administering a compound that modulates activity or abundance of one or more genes set forth in Table 1 or ortholog thereof.

An oligonucleotide designed to specifically detect or amplify a naturally occurring polymorphic variant of a polymorphism in a coding or noncoding portion of a gene set forth in Table I or ortholog thereof, or a polymorphic variant of a polymorphism in a genomic region linked to such a gene, wherein the gene or a portion thereof is coincident with a chronological life span disease, disorder or related disease or disorder.

A method of evaluating the effect of a chronological life span bioactive agent comprising:

• a) administering the bioactive agent to a mammal;
• b) removing a cell sample from the mammal;
• and c) determining the expression profile of the cell sample.

An array of probes, comprising a support bearing a plurality of nucleic acid probes complementary to a plurality of mRNAs fewer than 1000 in number, wherein the plurality of mRNA probes includes an mRNA expressed by at least one GLN3, LYS12, YG1007W, MEP2, RPP2A, MEP3, TEF4, GTR2, YGR054W, RTG2, DAL80, AGP1, GTR1, YBR077C, RPS25A, and TOR1 gene, or ortholog thereof.

A bioactive agent that extends life span by inhibiting the TOR pathway.

A bioactive agent that extends life span by inhibiting the TOR pathway in a model organism.

A chronological life span nucleic acid having a sequence at least 95% homologous to a sequence of a nucleic acid of Table 1 or ortholog thereof, or its complement.