[Biological aspects of longevity and ageing]

Abstract

Despite very different life expectancies, a 2-year-old mouse, a 12-year-old dog, a 32-year-old chimpanzee or an 80-year-old man will share many common deficits such as a reduction in tissue elasticity, immunological responses, muscular strength, sensory perceptions, reflexes, as well as memory losses and increase of age-associated diseases (osteoporosis, osteoarthritis, type II diabetes, cardiovascular diseases, cataract and macular degeneration, neurodegenerative diseases, to name only a few...). With the increase of life expectancy in human species, ageing has become a major concern for the society, both at the human and financial level. The main challenge for biologists studying ageing is to understand how the multiple effects quoted above, so easily identifiable in various species, are nonetheless so coordinate among individuals of a given species. The acquisition of this fundamental knowledge will be essential to reach the ultimate goal of healthy ageing for human populations. At the present time, three types of recent developments on ageing research can be distinguished: 1) A consensus on evolutionist theory of ageing is developing. This theory is based on the fact that long-lived species usually arise from protected ecological niches. It implies that phenotypes which are expressed late in "aged survivors" are beyond natural selection. So, alleles underlying this late expression being adaptive or not ("good" or "bad"), contribute only slightly to the pool of genes of the following generation. 2) Study of laboratory models like the nematode C. elegans or fly D. melanogaster have enabled the observation that single-gene invalidation can increase lifespan. Interestingly, some of these changes seem to imply a common process through insulin/IGF-1 (insulin like growth factor-I) orthologue, energy metabolism and growth implicated hormones, as well as protection against free radicals. 3) In the mouse, several genes mutation increase lifespan and are associated with a decrease in growth hormone (GH) secretion as well as its main effector IGF-1. The study of such transgenic mutants, in parallel with the well-known effect of the caloric restriction on ageing, open several tracks which should allow determining common mechanisms which regulate the mammalian lifespan.