Ageing, gerontogenes, and hormesis.

Evolutionary theories of ageing and longevity argue against the existence of specific genes that cause ageing. However, genes whose altered activity influences ageing and longevity, may be termed gerontogenes. Several putative gerontogenes have been identified in various ageing systems, including the Drosophila, budding yeast, nematodes and cells in culture. Since ageing is characterized by a progressive failure of maintenance and repair, it is reasoned that genes involved in homeodynamic repair pathways are the most likely candidate gerontogenes. A promising approach for the identification of critical gerontogenic processes is hormesis-like positive effects of stress. Stimulation of various repair pathways by mild stress has significant effects on delaying the onset of various age-associated alterations in cells, tissues and organisms.

Is gene therapy for aging possible?

Throughout human history, search for means to prevent or slow down aging has followed three main lines--(1) removing waste products and cleansing impurities; (2) using products of plants and animals as medicine; and (3) compensating for decrease in various hormones, vitamins and other chemicals in the body. Even in modern times, immense popularity of various spas and water therapies is an example of the first type of anti-aging approach for which there are no real scientific basis. Some preliminary support from laboratory and/or clinical tests is available for various herbal and other medicinal plant products, such as ginseng, ginkgo biloba and garlic, as nutritional supplements. Replacement therapy, especially hormonal replacement therapy as an anti-aging treatment has been used and misused for quite some time.

Cellular and molecular determinants of ageing.

The highly complex nature of the process of ageing implicates both genetic and epigenetic causative factors. A progressive failure of maintenance underlines and typifies this process. The instability of the nuclear and the mitochondrial genomes is an important determinant of ageing. Infidelity and misregulation of genetic information transfer, loss of cellular proliferative capacity, altered cellular responsiveness and defective pathways of signal transduction are major aspects of the failure of homeostasis. These are also the basis of age-related diseases and impairments, such as osteoporosis, arthritis, immune deficiency, altered drug clearance and altered functioning of the brain. Studies directed towards understanding the mechanisms of interaction and inter-dependence of various genes involved in maintenance and repair networks are the most promising research strategies for identifying gerontogenes.