Gene Therapy for Ageing: Mission Impossible?

Abstract

The modulation of ageing and lifespan has occupied the human mind since its inception. Throughout human history, the search for means to prevent or retard ageing has followed three main directions: (i) cleansing from impurities and wastes; (ii) nutritional supplements, including the use of medicinal plants; and (iii) replacement therapy. The immense popularity of various spas and water therapies even today, is an example of the first type of anti-ageing approach. The claims made for various herbal and other medicinal plant products, such as ginseng, ginkgo biloba and garlic, as nutritional supplements and anti-ageing drugs have received some support, however preliminary, from laboratory and/or clinical tests. Replacement therapy, especially hormonal replacement therapy as an anti-ageing treatment has been used and misused for quite some time. Various therapeutic procedures have been followed to replace the lost hormones, such as gland transplantation, secretory-cell injections and hormone injections. Whereas many of these approaches, such as monkey testicle transplants in the 1950s, have been frauds [1], others have been refined to some extent and are still in use. For example, the injection of biosynthetic human growth hormone for six months in elderly men resulted in some increase in lean body mass, a decrease in adipose-tissue mass, and a slight increase in vertebral bone density [2]. Similarly, there have been some claims regarding the anti-ageing effects of dehydroepiandrosterone (DHEA), which is the primary precursor of sex steroids [3]. Recently, the so-called sleep hormone melatonin has received much attention for its role as an anti-ageing hormone [4]. However, several questions remain unanswered regarding the wider applicability of such approaches because of our present lack of understanding of the regulation of synthesis of various hormones, their modes of action, metabolism and interrelations with other hormones. Experimentally, the most effective anti-ageing and lifeprolonging strategy has proved to be calorie restriction. A large number of studies have established that calorie restriction delays ageing and prolongs the lifespan of various animals [5]. Although most of the studies on dietary restriction and ageing have been performed on rats and mice, results have started to emerge from studies on long-term dietary restriction of non-human primates, rhesus monkeys [6, 7]. However, at this stage, it is very difficult to say what kind of voluntary dietary-restriction regimes will have similar anti-ageing and life-prolonging effects in human beings, considering that there are significant differences in the biology and, perhaps more importantly, the sociology of human beings as compared with other animals.