Molecular Biology of Aging

Manal El Ejel

ABSTRACT I begin my review paper with a little introduction about the molecular biology of aging and then I discuss the theories and the techniques used.

INTRODUCTION

As life starts there is limits to it, it reaches an end. The same goes for elderly people who reach this point due to different factors that increase or decrease the duration of life.

After many studies molecular biology is deemed the most important assay in relation to senescence. So we study what are the causes of aging, such as life span, protein, foods, in order to manufacture geriatric medicines.

According to many authors immortality is defined such that "intestinal toxins or lactobacillus may have a role in aging process" according to Elie Metchnikoff, while Anna Aslan popularized "Gerovital h3 (a mixture of procaine, benzoic acid, and potassium met bisulfate) as a rejuvenating agent".

Aging theories are studied by division in to population, organ, and cellular based theories. A variety of molecular techniques helps in the studies of molecular biology of aging.

Molecular techniques are powerful tools which allow the probing of basic cellular functions and elucidate the mechanisms of disease states. These techniques have already been proven to be extremely useful in making diagnosis and treating some diseases. Protein synthesizing machinery is the principal of cellular function of the aging process due to its relation with transcription and translation of DNA in nucleus of eukaryotic cells^(1-2).

The study of genetics of protein synthesis is divided in to quantization of proteins, mRNA, transcription. Thus the cause can be achieved more simply.

Protein: Is estimated either by measuring the protein mass (by Elissa, Electrophoresis, western Blot analysis) or by estimating its activity by measuring the rate of reaction and disappearance of cofactors.

The same goes for protein mRNA which is tested, in order to examine the activity of genes by translating its mRNA into protein. The common procedure used to analyze specific mRNA sequence is northern gel analysis⁽⁴⁾. There are two other methods for identifying DNA regulating protein system, by foot printing or gel retard action⁽⁵⁾.

For transcription which becomes popular in the study of hormonal regulation of gene expression, according to nuclear "Run-on" assay or to chloramphenicol acetyl transferase (CAT) ASSAY.

RELP "Restriction Fragment Length Polymorphism"

This is used to detect mutation within a gene that will result in dna polymorphisim. Studies of the structural changes in chromatin is by two techniques: Nuclease Digestion Studies and DNA unwinding assays.

Studies of the DNA strand Breaks/Repair by: alkaline and neutral sucrose gradient sedimentation techniques and other various techniques that study DNA damage such as Methylation status of the DNA which is associated with transcriptional activity of certain genes⁽³⁾.

The study of cellular-based theories and reactions in our body with age, lead to many disturbances of the body as AGE which serve as a biomarker of aging⁽⁷⁾. Studies, conducted on rats, of drosophila indicate the age-related reduction in protein synthesis⁽⁸⁾ conditions such as (nutrition, endocrine and organ system stasis) may potentially confound the interpretations of age-related changes in specific mRNA level.

A good example of altered mRNA stability with age in the increasing albumin mRNA levels is the liver aged animals⁽⁹⁾. These are not due to enzyme changes but due to chromatin bound neuronal RNA polymerase which decrease in aging neurons. Age-related changes in chromatin melting point increase with age.

DNA winding rate in alkali containing high concentration of urea is also reduced in aged animals.

Recent evidence for genetic basis of cellular aging:

1. RNA with inhibitory activity on cellular growth in vitro.
   
2. The recessive phenotype of immortality in cultured cells.
   
3. The expression of c-fos oncogene has been linked to stimulation of DNA synthesis by growth factors.

CONCLUSION

Many studies and techniques are issued in order to promote a more significant picture about age in relation to molecular genetics but, always there are elements missing.

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