Age-modified cells and methods for making age-modified cells

Abstract

Provided are age-modified cells and method for making age modified cells using progerin or a progerin-like protein. The aging and/or maturation process can be accelerated and controlled for young and/or immature cells, such as a somatic cell, a stem cell, a stem cell-derived somatic cell, including an induced pluripotent stem cell-derived cell, by contacting with progerin or a progerin-like protein. Methods described by the present disclosure can produce age-appropriate cells from a somatic cell or a stem cell, such as an old cell and/or a mature cell. Such age-modified cells constitute model systems for the study of late-onset diseases and/or disorders.

What is claimed is: 
     
         1 . A method for producing a cell exhibiting at least one chronological marker, said method comprising: contacting a cell that is deficient in said one or more chronological markers with a progerin-like protein in an amount and for a period of time sufficient to induce the production of said at least one chronological marker. 
     
     
         2 . The method of  claim 1 , wherein said cell that is deficient in said at least one chronological marker is a stem cell. 
     
     
         3 . The method of  claim 1 , wherein said cell that is deficient in said at least one chronological marker is a somatic cell. 
     
     
         4 . The method of  claim 3  wherein said somatic cell is produced by a method comprising contacting a stem cell with one or more differentiation factors, wherein said differentiation factors promote the differentiation of said stem cell into said somatic cell. 
     
     
         5 . The method of  claim 4 , wherein said stem cell is an induced pluripotent stem cell (iPSC). 
     
     
         6 . The method of  claim 5 , wherein said somatic cell is an “old” somatic cell. 
     
     
         7 . The method of  claim 5 , wherein said somatic cell is selected from the group consisting of a fibroblast cell, a liver cell, a heart cell, a CNS cell, a PNS cell, a kidney cell, a lung cell, a hematopoietic cell, a pancreatic beta cell, a bone marrow cell, an osteoblast cell, an osteoclast cell, an endothelial cell. 
     
     
         8 . The method of  claim 7 , wherein said CNS cell is selected from the group consisting of a neural progenitor, a neuron and a glial cell. 
     
     
         9 . The method of  claim 7 , wherein said CNS cell is a midbrain dopamine (mDA) neuron cell. 
     
     
         10 . The method of  claim 1 , wherein said contacting is conducted in vitro or ex vivo. 
     
     
         11 . The method of  claim 1 , wherein said progerin is human progerin. 
     
     
         12 . The method of  claim 1 , wherein said at least one chronological marker is selected from the group consisting of an age-associated marker, a maturation-associated marker, and a disease-associated marker. 
     
     
         13 . The method of  claim 12 , wherein said at least one chronological marker is an age-associated marker selected from Table 2 or Table 3. 
     
     
         14 . The method of  claim 1 , wherein the progerin-like protein is exogenous to the cell. 
     
     
         15 . The method of  claim 14 , wherein the exogenous progerin-like protein is expressed by a polynucleotide introduced to the cell. 
     
     
         16 . The method of  claim 1 , wherein the progerin-like protein is endogenous to the cell. 
     
     
         17 . The method of  claim 16 , wherein the endogenous progerin-like protein is expressed by modifying the splicing pattern of the LMNA RNA of said cell.