A life-span study was carried out on longevity, pathologic lesions, growth, lean body mass and selected aspects of muscle of barrier-maintained SPF Fischer 344 rats fed either ad libitum (Group A) or 60% of the ad libitum intake (Group R). Food restriction was as effective in prolonging the life of already long-lived SPF rats as previously shown for rats maintained in conventional facilities. Food restriction not only increased the mean length of life but also acted to extend life span since more than 60% of the Group R rats lived longer than the longest lived Group A rat. Renal lesions occurred at an earlier age in Group A rats than in Group R rats and progressed more rapidly. Death of most Group A rats was associated with severe renal lesions while few Group R rats showed such lesions at death. Food restriction was also found to delay or prevent interstitial cell tumors of the testes, bile duct hyperplasia, myocardial fibrosis and myocardial degeneration. Gastrocnemius muscle mass declined in advanced age and food restriction delayed this decline. Interestingly, however, lean body mass did not progressively decline with increasing age but rather decline occurred only after the onset of the terminal disease process.

Male Fischer 344 rats were either fed ad libitum (Group A) or 60% of the ad libitum intake (Group R) starting at 6 weeks of age; the latter is a life prolonging food restriction. Total adipose mass increased with increasing age in both Group A and Group R rats until about 70% of the life span after which it declined. The results indicate that the lower adipose mass of the Group R rats is probably not related to life prolongation. Adipocyte hypertrophy is involved in growth of the epididymal and perirenal depots in adult Group R rats and is the sole basis of epididymal depot growth in adult Group A rats. Increasing adipocyte number is the sole basis of perirenal depot growth in adult Group A rats and is involved in the growth of both depots in adult Group R rats. Decreasing adipose mass during senescence involves decreasing mean adipocyte volume but not a decrease in the adipocyte number.

In vitro passage of the Patton strain of herpes simplex virus type 1 (HSV-1-P) in the presence of acycloguanosine (ACG) led to the emergence of a highly drug-resistant strain (HSV-1-P-ACG-R). Over 1% of virions in 6 of 15 HSV strains tested were able to form plaques in the presence of 10 mumol of ACG on first exposure to the drug. Therefore, there exists among HSV strains a broad range of susceptibilities to ACG, and some strains contain particles which are partially resistant to ACG before ever contacting the drug. HSV-1-P-ACG-R was partially resistant to iododeoxyuridine; conversely, iododeoxyuridine-resistant virus was highly resistant to ACG. ACG-resistant virus (HSV-1-P-ACG-R) was equal to its parent strain (HSV-1-P) in susceptibility to adenine arabinoside. The HSV-1-P-ACG-R strain produced corneal lesions in rabbits which were completely refractory to topical treatment with 1% unguent ACG, but responsive to 3% ACG. Partially resistant HSV could be isolated from the eyes of rabbits infected with ACG-susceptible virus and treated topically with either 1 or 3% ACG for 6 days.

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