The Effect of Age on Tissue Protein Synthesis

Abstract

Currently available data on the effect of age in tissue protein synthesis and turnover are reviewed and experimental evidence is presented on age changes in amino acid incorporation by rat liver purified microsomes. It has been observed that the purification of ‘crude’ microsomal preparations from contaminating lysosomes by density gradient centrifugation is accompanied by an increase in amino acid incorporatmg activity of the microsomal preparations, no matter whether these are prepared from young or from old animals, and that the amino acid incorporating activity of rat liver purified microsomes prepared from old animals (19–25 months) is lower than that prepared from adult animals (7–11 months) which in turn is lower than that from young animals (2–3 months), no matter whether the activity is expressed per mg of microsomal protein or per mg of microsomal RNA. Also, experimental evidence is presented which is consistent with the presence in liver purified microsomes of heat-labile inhibitor(s) of amino acid incorporation, and with their accumulation (or increase in effect) in the microsomes with the age of the animal. Several major features of the decline with age in tissue protein synthesis are outlined and a number of possible factors or causes, beside the microsomal inhibitor(s), contributing to the decline with age in tissue protein synthesis, are discussed.

Protein Synthesis and Degradation During Aging and Senescence

“…Kurtz ( I 975) found an age-related decline in polyphenylalanine synthesis with liver microsomes from C57BL/6J mice of I , 2 , 14, 27, and 31 months of age. Hrachovec (1971) observed an age-associated 5 0 0 /~ decrease in liver protein synthesis using microsomes isolated from male albino rats of ages 2-3, 7-1 I , and 19-25 months. Other workers also found a decline in protein synthesis with liver microsomes isolated from adult and senescent rats (Hrachovec, 1969;Buetow & Gandhi, 1973;Comolli, 1973;Junghahn & Bielka, 1974;Hellthaler et al, 1976;Buetow et al, 1977).…”

“…These results are in contradiction to a large body of literature indicating a decline in brain protein synthesis after birth. Such age-related decreases have been observed in rats (Murthy & Rappoport, 1965;Yamagami, Fritz & Rappoport, 1966;Andrews & Tata, 1971 ;Barra et al, 1973;Dunlop, Van Elden & Lajtha, 1977b), and mice (Johnson & Belytschko, 1969;Lerner & Johnson, 1970, 1971. The decreases in brain protein synthesis were reported to occur primarily during the first 3 0 days after birth (Lerner & Johnson, 1970, 1971Andrews & Tata, 1971).…”

“…The use of cell-free systems is also of limited value (see Section VII (7)). Protein synthesis by isolated microsomes is linear for only about 5 min, followed by a plateau after about 20 min of incubation (Mainwaring, 1969;Hrachovec, 1971;Buetow & Gandhi, 1973;Chen et al, 1973;Layman et al, 1976). Moreover, the in vitro rate of protein synthesis by liver is only I yo of the rate observed in vivo (Henshaw et al, 1971 ;Millward et al, 1973;Waterlow, 1975).…”

Hepatocyte fine structure during maturation and senescence

“…Most studies have demonstrated an age-related decline in cell-free protein synthesis using microsomes, ribosomes, or isolated hepatocytes from rodent livers (Richardson et al, 1985;Horbach et al, 1987;Mainwaring, 1969;Hrachovec, 1971;Buetow and Ghandi, 1973;Comolli, 1973;Kurtz, 1978;Viskup et al, 1981). Several investigators have reported a marked increase in the synthesis of specific hepatic proteins, particularly albumin, during late senescence (Chen et al, 1973;van Bezooijen et al, 1976;Van Bezooijen and Knook, 1977).…”

“…Age-dependent alterations in protein metabolism, especially hepatic protein synthesis, have been subjected to considerable study (for reviews, see Richardson, 1981;Richardson and Birchenall-Sparks, 1983;Richardson et al, 1985). Most studies have demonstrated an age-related decline in cell-free protein synthesis using microsomes, ribosomes, or isolated hepatocytes from rodent livers (Richardson et al, 1985;Horbach et al, 1987;Mainwaring, 1969;Hrachovec, 1971;Buetow and Ghandi, 1973;Comolli, 1973;Kurtz, 1978;Viskup et al, 1981). Several investigators have ANIMAL AGE (Months) Fig.…”