Immunological assessment of ageing: emergence of scrapie-like antigens

Certain morphological similarities between scrapie--a naturally occurring disease of sheep, long looked upon as a paradigm of 'slow infections'--and the ageing process in normal animals led to a study of the development of new antigens both in scrapie-affected animals and in normal mice and humans. It was found that with advancing age new antigen(s) identical with, or similar to, those occurring in scrapie (where the time co-ordinate of aging in the brain seems foreshortened) make their appearance both in mice and humans, and lead to special sensitization of lymphocytes in normal guinea pigs injected with old tissues so that the difference in the lymphocyte response to scrapie or normal test antigen (SND) is exaggerated. It may be that the 'new antigen(s)' depend upon molecular rearrangement of membrane structure perhaps induced by an external agent (not necessarily a virus). Thymectomy in the new-born mouse or rat produces in many cases 'runting' which appears in many ways to be a caricature of ageing. The SND is greatly increased at a very early age by the process of thymectomy and there is evidence that it may be held up by implantation of neonatal thymus tissue into the deprived animals. During the first years of life there appears to be the same difference in the constitution of erythrocyte membranes which moves towards the adult type towards puberty. This may be part of a general phenomenon of significance in the physiopathology of childhood. Finally the analogy between the changes occurring the kuru-scrapie-CJD complex and old age, and the somewhat new antigenic materials emerging in them must not be taken to imply that any virus is per se concerned with the ageing process. No 'virus of old age' is known. It seems to the writer that it is much more likely that ageing (and the diseases mentioned) are associated with membrane steric rearrangement (which can be transmitted--but not necessarily by a classical virus). In the writer's opinion it is a reasonable hypothesis to entertain that as the cell 'ages' and becomes a less favourable habitat for viruses (normally built into its DNA and/or RNA) they emerge, may take on recognizable forms, and indeed may attempt to seek younger and better homes. No doubt we all carry a load of such inapparent 'viruses' which (like our fellow humans) are likely to abandon us in old age. It is a commonplace that we have an embarras de richesse of viruses and it may be some of these which have been 'isolated' from old tissues.