Control of cell proliferation in senescent cells

The discussions described briefly above have provided an agenda for research on aging at the molecular and cellular level for several years to come. Of central importance is the need to distinguish, at the cellular level, aging from terminal differentiation and disease. Are there terminal differentiation functions that we misinterpret as aging? Are there regulatory pathways of aging? Is cell senescence a true opposite of tumorigenesis? What exactly is the G₁/S block? Why are most but not all G₁ genes expressed in senescent cells? What roles do changes in RNA processing and protein synthesis play in cell senescence? How is down-regulation of tissue-specific genes effected? These are the critical questions at the cellular level. Of equal importance is the need to establish correspondence between cell senescence phenomena and organismal aging. The similarities between cells aged in culture and cells aged in vivo are encouraging, but cell senescence in culture is neither the ideal nor the only model system for studying aging. Continued and expanded efforts to study aging in vivo in a variety of animal models are clearly needed. Finally, of utmost importance is the need to elucidate how caloric restriction slows the rate of aging and retards the onset of age-related disease. Although this is a whole body phenomenon, it seems likely that understanding how this works will shed considerable light not only on aging but on tumorigenesis as well.