The gradual appearance of senescent cells may contribute to the development of age-related disease. However, the presence of disease by other mechanisms may result in accelerated senescence. Disease may cause tissue damage which leads to cellular turnover for the purpose of replacing lost cells. This exhausts the replicative capacity of the cells and accelerates the appearance of senescent cells. For example Goldstein and co-workers (1978) looked at the replicative lifespan of fibroblasts from normal, prediabetic, diabetic donors. Diabetes mellitus is a common genetically determined disorder associated with reduced life expectancy. This study confirmed earlier findings that there is an inverse correlation between donor age and replicative lifespan, but emphasised the importance of physiological state of the donors. Normal cell strains showed significantly better growth capacity than diabetic and prediabetic cells. The results indicated that with an increasing predisposition to diabetes, there is a progressive decrease in replicative capacity.
Another group investigating atherosclerosis took vascular smooth muscle cells (VSMC) from human atherosclerotic plaques and grew them in culture (Bennett et al, 1998). Results showed that VSMCs taken from plaques have lower rates of proliferation and underwent senescence earlier than cells derived from normal vessels.
A more recent study looked at the replicative capacity of osteoblasts in Rheumatoid arthritis (RA) compared with Osteoarthritis (OA) (Yudoh et al, 2000). The results indicated that the replicative capacity of osteoblasts decreased gradually with donor age and this decrease was higher in RA patients than with OA patients at any donor age. They also reported an increase in senescent osteoblastic cells with age in both groups in which the rate of expression of senescent cells was higher in RA patients than with age-matched OA patients.
Tesco et al (1993) looked at the replicative capacity of fibroblasts in patients with familial Alzheimer’s disease (FAD) to examine whether features compatible with a systemic premature aging were present. Data showed that there was no significant difference in replicative capacity of fibroblasts between FAD patients and controls. This is not a surprising result, since the fibroblasts studied are unrelated to the development of FAD and if features of premature ageing were present they would have most likely manifested themselves as other diseases other than just Alzheimer’s. For example, Werner’s syndrome is a premature ageing disorder which displays a multitude of age-related afflictions including diabetes and heart disease (Kipling and Faragher, 1997). When fibroblasts were taken from patients with Werner’s syndrome and grown in culture, the number of population doublings achieved was smaller compared with normal cells of a similar chronological age (Martin et al, 1970)
These studies suggest that disease is an important factor contributing to the exhaustion of the replicative capacity of cells. However, it is possible that some diseases arise as a result of the gradual increase in senescent cells with time. It is also possible that unknown factors result in accelerated senescence, which subsequently manifests itself as a biological impairment or disease.
Factors, other than disease, which may contribute to cellular injury and cell loss, may be environmental such as UV radiation, chemical damage from smoking and foods, and normal biological damage from general wear and tear.