The present invention provides new and advantageous methods, compositions,
cell constructs and animal models related to inhibiting the senescence of
vertebrate cells and vertebrate organisms based on the use of SIRT1
polynucleotides and polypeptides, as well as mutant SIRT1 polynucleotides
and polypeptides. The invention provides polynucleotides that encode
variants and fragments of SIRT1 polypeptides, and also provides variant
SIRT1 polypeptides and fragments thereof. Additionally the invention
provides a method of inhibiting or delaying the expression in a
vertebrate cell of a protein having biological activity associated with
loss of population doubling in the cell. The invention further provides a
method of treating a pathology, a disease or a medical condition in a
subject, wherein the pathology responds to an SIRT1 polypeptide. The
invention also provides a vertebrate cell that incorporates a
heterologous nucleic acid encoding a variant of SIRT1, or a fragment
thereof, as well as a transgenic mammal a majority of whose cells harbor
a transgene including a nucleic acid sequence encoding an SIRT1
polypeptide. The invention also provides an antibody that binds
immunospecifically to a variant SIRT1 polypeptide or a fragment thereof,
and a method of determining whether the amount of an SIRT1 polypeptide in
a sample differs from the amount of the SIRT1 polypeptide in a reference.
The invention further provides a method of contributing to the diagnosis
or prognosis of, or to developing a therapeutic strategy for, a disease
or pathology in a subject, wherein the disease or pathology responds to
treatment with an SIRT1 polypeptide and wherein the amount of SIRT1
polypeptide in the pathology is known to differ from the amount of the
SIRT1 polypeptide in a nonpathological state.
