The biochemistry of mammalian senescence

Senescence is a process which, until quite recently, has been the subject of little scientific investigation. Even the word "senescence" is difficult to define, and complex methodological pitfalls have impeded progress. In the past few years, there have been exciting advances in understanding the physiological, cell biological, biochemical, and molecular biological nature of senescence. Changes in membrane function, protein synthesis, DNA structure (including glycosylation, altered tertiary structure, free-radical effects, and loss of telomeric DNA), and changes in gene regulation with age are reviewed. Recent work on changes in responses to transcriptional regulatory proteins and cellular senescence factors, some of which have been identified, is particularly promising and leads to the conclusion that senescence, at least in part, is a programmed process. Despite these advances, the fundamental cause of senescence remains elusive but might, as in the case of other biological processes which are phylogenetically widespread, turn out to be quite simple, and perhaps, even modifiable.