The specific activity of aldolase in the livers of old and young rats.

The catalytic activity of liver fructose-biphosphate aldolase (EC 4.1.2.13) of young and old rats in units per manomole sequence has been calculated. No evidence of the accumulation with age of altered enzyme molecules of low catalytic activity was obtained. This is contrary to results obtained using mice and rabbits and indicates that the accumulation of altered enzymes may not always be associated with aging. The possibility that altered proteins are formed, but do not accumulate, cannot be ruled out.     

Epididymal sperm profiles in young adult,middle-aged,and testosterone-supplemented old rats

Both ejaculated semen and epididymal contents from an individual male contain sperm that differ in various physicochemical characteristics. An experiment is reported in which epididymides from rats 5–24 months old were subjected to density gradient centrifugation to separate gametes of different stages of maturity. The research was designed to examine typical changes in “profiles” of sperm maturity during the reproductive lifetime of rats. Also, testosterone complexed with cyclodextrin that mimics the episodic release of the endogenous hormone was used to supplement the decreased circulating titers of some of the old males. Results revealed clear ontogenetic patterns of gradually decreasing reproductive competence as measured by absolute numbers of sperm, circulating levels of testosterone, and various other physiological markers of fertility. Sperm profiles also revealed age-specific changes with a shift toward progressively more mature, perhaps senile, gametes that begins at middle age. Testosterone supplementation (400 μg/kg b.w./day for 30 days) failed to restore sperm numbers or other measures of physiology in the old males, but the steroid modified sperm profiles to approximate more closely the profiles characteristic of young adult males than either untreated middle-aged or old males. The data were interpreted as suggesting that epididymal sperm profiles clearly identify males of different ages, and that the aging epididymis retains its capacity to respond to manipulations that modify the endocrine milieu.     

Colonic cell proliferation and growth fraction in young,adult and old rats

Colonic epithelial proliferation was investigated in three groups of rats, aged 3, 60 and 121 weeks. As reported in previous work, the crypts were markedly longer in the young rats, and the number of labelled cells per crypt was significantly greater. There was an upward movement of the marker positions derived from the distribution of labelled cells within the crypt of the young rats. This was a consequence of the increased crypt length, so that the growth fraction, as expressed as a percentage of crypt length, was the same. The proliferative changes between the young rats and the other aged rats were therefore effected by altering the size of the crypts, while maintaining the kinetic organisation. There was no evidence of any proliferative changes or changes in the growth fraction when the colons of the old rats were compared with those of the 60 week old rats.     

Colonic cell proliferation and growth fraction in young, adult and old rats.

Colonic epithelial proliferation was investigated in three groups of rats, aged 3, 60 and 121 weeks. As reported in previous work, the crypts were markedly longer in the young rats, and the number of labelled cells per crypt was significantly greater. There was an upward movement of the marker positions derived from the distribution of labelled cells within the crypt of the young rats. This was a consequence of the increased crypt length, so that the growth fraction, as expressed as a percentage of crypt length, was the same. The proliferative changes between the young rats and the other aged rats were therefore effected by altering the size of the crypts, while maintaining the kinetic organisation. There was no evidence of any proliferative changes or changes in the growth fraction when the colons of the old rats were compared with those of the 60 week old rats.     

Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

Marsh, Daniel R., David S. Criswell, James A. Carson, andFrank W. Booth. Myogenic regulatory factors during regeneration ofskeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270-1275, 1997.Myogenicfactor mRNA expression was examined during muscle regeneration afterbupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of thetibialis anterior muscle in the young rats had recovered to controlvalues by 21 days postbupivacaine injection but in adult and old ratsremained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA wassignificantly increased in muscles of young, adult, and old rats 5 daysafter bupivacaine injection. Subsequently, myogenin mRNA levels inyoung rat muscle decreased to postinjection control values byday 21 but did not return to controlvalues in 28-day regenerating muscles of adult and old rats. Theexpression of MyoD mRNA was also increased in muscles atday 5 of regeneration in young, adult,and old rats, decreased to control levels by day14 in young and adult rats, and remained elevated inthe old rats for 28 days. In summary, either a diminished ability todownregulate myogenin and MyoD mRNAs in regenerating muscle occurs inold rat muscles, or the continuing myogenic effort includes elevatedexpression of these mRNAs.

     

RNA polymerase I and II activities in different brain regions of young, adult, and old rats

The activities of RNA polymerase I and II were assayed in nuclei isolated from different regions (cerebral cortex, cerebellum, hypothalamus, hippocampus, corpus striatum and pituitary) of brains from young (10 days), adult (6 months), and old (2 years) rats. The RNA polymerases I and II activities generally increased during maturation, i.e., from 10 days to 6 months of postnatal age and then showed a decrease from 6 months to 2 years of age in all the regions except in cerebral cortex where the RNA polymerase II activity was highest at 10 days but showed a gradual decrease through the lifespan up to 2 years.     

Effects of exercise on plasma lipoprotein levels and endothelium-dependent vasodilatation in young and old rats

Effects of treadmill exercise (1 h.day-1 for 12 weeks) on the mechanical properties of isolated aortae and plasma concentrations of low and high density lipoprotein cholesterols ([LDL-C]pl and [HDL-C]pl, respectively) were investigated in young (16 weeks) and old (98 weeks) rats. With aging, [LDL-C]pl increased and acetylcholine (ACh) elicited greater endothelium-dependent relaxations of the aorta in old rats than in young rats. Also, in all groups of rats tested (young, old, exercised and nonexercised), the increase in the [LDL-C]pl correlated with an increase in the sensitivity of relaxation of the aorta to ACh. On the other hand, a greater [HDL-C]pl was associated with a smaller relaxation response to ACh in young rats only when exercised and nonexercised groups were combined. The increase in [HDL-C]pl with aging, however, did not correlate with the extent of ACh-induced relaxation. Exercise in old rats reduced [LDL-C]pl and the extent of ACh-induced relaxation of the aorta. Therefore, [LDL-C]pl appeared to be closely related to the extent of endothelium-dependent relaxation in response to ACh in the aorta. The [LDL-C]pl also correlated with the gain in mass of the rat. Exercise in old rats reduced the body mass and was accompanied by a decrease in [LDL-C]pl.     

The effects of acetylsalicylic acid on phosphoenolpyruvate carboxykinase activity and acinar heterotopy in livers from juvenile and adult rats

Summary Male and female juvenile as well as adult rats were treated with acetylsalicilic acid in order to examine the effect of the drug on over-all activity and activity distribution of phosphoenolpyruvate carboxykinase (PEPCK) in the liver acinus. Upon administration of acetylsalicilic acid PEPCK activity increased in juvenile males and adult females, but was reduced in juvenile females and adult males. The periportal-perivenous activity gradient along the sinusoidal length, which is flatter in untreated juvenile rats compared to the livers of adult rats, was distinctly steepened by acetylsalicilic acid treatment. Acetylsalicilic acid did not affect the gradient in adult rats.     

The effects of acetylsalicylic acid on phosphoenolpyruvate carboxykinase activity and acinar heterotopy in livers from juvenile and adult rats

Male and female juvenile as well as adult rats were treated with acetylsalicylic acid in order to examine the effect of the drug on over-all activity and activity distribution of phosphoenolpyruvate carboxykinase (PEPCK) in the liver acinus. Upon administration of acetylsalicylic acid PEPCK activity increased in juvenile males and adult females, but was reduced in juvenile females and adult males. The periportal-perivenous activity gradient along the sinusoidal length, which is flatter in untreated juvenile rats compared to the livers of adult rats, was distinctly steepened by acetylsalicylic acid treatment. Acetylsalicylic acid did not affect the gradient in adult rats.     

The comparison of multipotential for differentiation of progenitor mesenchymal-like stem cells obtained from livers of young and old rats

The presence of stem cells differentiating to hepatocytes and cholangiocytes has been previously reported in livers of young rats. Here, we have isolated, cultured, and characterized mesenchymal stem cells (MSCs) from livers of young and old rats and tested their multipotential for differentiation. The mesenchymal stem cells in liver sections were identified by the presence of markers, respectively for primary stem cells Thy-1 and CD34, for differentiation to early cholangiocytes GST and CK19, and for differentiation to hepatocytes GSTalpha and CK18. Ki67 was detected as the cell proliferation marker. Cells isolated from livers of either age group were tested in a culture for their viability following storage and were characterized for the presence of most of the markers detected in cells in situ. The results revealed age-dependent changes in the number of recovered primary MSCs. In both age groups we have observed cells changing under differentiating conditions to liver cell lineages, such as cholangiocytes and hepatocytes, as well as to non-liver cells such as adipocytes, astrocytes, neuroblasts, and osteoblasts. Our data revealed that from the livers of rats 20 months and older the primary MSCs could be isolated and expanded; however, they were significantly fewer, even though their differentiation multipotential was preserved. The mechanism involved in the differentiation of liver MSCs seemed to depend on a constellation of signals in Notch signalling pathways. Thus, our results support the idea of potential use of liver as a source of MSCs, not only for liver reconstruction but also for cell therapy in general.