Composition for reducing cellular senescence level including activity inhibitor inhibiting dcun1d3 activity or expression inhibitor inhibiting expression of dcun1d3-encoding gene and use thereof

Abstract

Provided is a composition and method for reducing a cellular senescence level by inhibiting the activity or expression of one or more of DCUN1D3 protein or gene encoding same and a polynucleotide having a nucleotide sequence of SEQ ID NO: 5, as well as a method of treating a disease or a disease symptom associated with an increased cellular senescence level in a mammal.

What is claimed is: 
     
         1 . A composition comprising an activity inhibitor inhibiting activity of one or more of DCN1, defective in cullin neddylation 1, domain containing 3 (DCUNID3) protein and a polynucleotide having a nucleotide sequence of SEQ ID NO: 5, or an expression inhibitor inhibiting expression of one or more of a gene encoding DCUN1D3 and a gene encoding the nucleotide sequence of SEQ ID NO: 5. 
     
     
         2 . The composition of  claim 1 , wherein the expression inhibitor is small interference RNA (sRNA), small hairpin RNA (shRNA), microRNA (miRNA), antisense oligonucleotide, or a combination thereof. 
     
     
         3 . The composition of  claim 2 , wherein the shRNA includes a nucleotide sequence of SEQ ID NO: 1 and a nucleotide sequence of SEQ ID NO: 2. 
     
     
         4 . The composition of  claim 1 , wherein the activity inhibitor is small interference RNA (sRNA) against a polynucleotide having a nucleotide sequence of SEQ ID NO: 5, small hairpin RNA (shRNA), antisense oligonucleotide, or a combination thereof. 
     
     
         5 . A method of reducing a cellular senescence level in a mammal, the method comprising administering an activity inhibitor inhibiting activity of one or more of DCUN1D3 protein and a polynucleotide having a nucleotide sequence of SEQ ID NO: 5, or an expression inhibitor inhibiting expression of one or more of a gene encoding DCUN1D3 and a gene encoding the nucleotide sequence of SEQ ID NO: 5 to the mammal to reduce the cellular senescence level. 
     
     
         6 . A method of treating a disease or a disease symptom associated with increased cellular senescence level in a mammal, the method comprising administering an activity inhibitor inhibiting activity of one or more of DCUN1D3 protein and a polynucleotide having a nucleotide sequence of SEQ ID NO: 5, or an expression inhibitor inhibiting expression of one or more of a gene encoding DCUN1D3 and a gene encoding the nucleotide sequence of SEQ ID NO: 5 to the mammal to treat the disease or the disease symptom associated with increased cellular senescence level. 
     
     
         7 . The method of  claim 6 , wherein the expression inhibitor is small interference RNA (sRNA), small hairpin RNA (shRNA), microRNA (miRNA), antisense oligonucleotide, or a combination thereof. 
     
     
         8 . The method of  claim 6 , wherein the activity inhibitor is small interference RNA (sRNA) against a polynucleotide having a nucleotide sequence of SEQ ID NO: 5, small hairpin RNA (shRNA), antisense oligonucleotide, or a combination thereof. 
     
     
         9 . The method of  claim 6 , wherein the disease or the disease symptom associated with increased cellular senescence level is skin wrinkles, wound healing declines, sarcopenia, muscular dystrophy, early senescent symptom (Hutchinson-Gilford progeria syndrome), or a combination thereof. 
     
     
         10 . The method of  claim 6 , wherein the disease or the disease symptom associated with increased cellular senescence level is a disease or a disease symptom associated with accumulation of lipofuscin. 
     
     
         11 . The method of  claim 10 , wherein the disease or the disease symptom associated with accumulation of lipofuscin is neuronal ceroid lipofuscinoses (NCL), age-related macular degeneration, neurofibrillary tangles, brown atrophy of the heart, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), acromegaly, denervation atrophy, lipid myopathy, or chronic obstructive pulmonary disease (COPD). 
     
     
         12 . A method of reducing a lipofuscin level in a mammalian cell, the method comprising administering an activity inhibitor inhibiting activity of one or more of DCUN1D3 protein and a polynucleotide having a nucleotide sequence of SEQ ID NO: 5, or an expression inhibitor inhibiting expression of one or more of a gene encoding DCUN1D3 and a gene encoding the nucleotide sequence of SEQ ID NO: 5 to a mammal to reduce the lipofuscin level in the cell. 
     
     
         13 . The method of  claim 12 , wherein the method is used to treat a disease or a disease symptom associated with increased lipofuscin level in a mammalian cell. 
     
     
         14 . A method of reducing a cellular senescence level in a cell, the method comprising inhibiting the activity or expression of DCUN1D3 and/or a polynucleotide having a nucleotide sequence of SEQ ID NO: 5 in the cell. 
     
     
         15 . The method of  claim 14 , wherein the cell is in a mammal. 
     
     
         16 . The method of  claim 15 , wherein the mammal is afflicted with a disease or a disease symptom associated with increased cellular senescence or accumulation of lipofuscin. 
     
     
         17 . The method of  claim 16 , wherein the disease or symptom is skin wrinkles, wound healing declines, sarcopenia, muscular dystrophy, early senescent symptom (Hutchinson-Gilford progeria syndrome), neuronal ceroid lipofuscinoses (NCL), age-related macular degeneration, neurofibrillary tangles, brown atrophy of the heart, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), acromegaly, denervation atrophy, lipid myopathy, or chronic obstructive pulmonary disease (COPD), or a combination thereof. 
     
     
         18 . The method of  claim 14 , wherein the activity or expression of DCUN1D3 and/or a polynucleotide having a nucleotide sequence of SEQ ID NO: 5 is inhibited in the cell by administering to the cell a small interference RNA (sRNA), small hairpin RNA (shRNA), microRNA (miRNA), antisense oligonucleotide, or a combination thereof, which hybridizes with a nucleotide sequence encoding DCUN1D3 or SEQ ID NO:5.