The anti-aging action of hypophysectomy in hypothalamic obese rats: Effects on collagen aging, age-associated proteinuria development and renal histopathology

Everitt, Arthur V.; Wyndham, Jennifer R.; Barnard, Dominique J.

doi:10.1016/0047-6374(83)90079-9

Cited by 23 publications

(8 citation statements)

References 23 publications

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“…This confirms earlier observa tions on other tissues showing that hypophy sectomy is superior to food restriction in inhibiting the ageing processes in tendon col lagen [61] and kidney [62] and reducing the frequency of gross pathology in old age in cluding hind leg muscle paralysis [63]. In hypophysectomized rats there is an absence of anterior pituitary hormones, while in foodrestricted animals there is a reduced level of these circulating hormones.…”

Section: Hypophysectomy and Food Restriction Effectssupporting

confidence: 78%

Morphometric Analysis of the Muscle Fibres of the Soleus Muscle of the Ageing Rat: Long-Term Effect of Hypophysectomy and Food Restriction

Shorey

Everitt²,

Armstrong³

et al. 1993

Gerontology

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This communication reports on the effects of ageing, hypophysectomy and food restriction on the fibre sizes of the soleus muscle which is primarily concerned with posture. The results reported here are compared with those previously shown for the gastrocnemius muscle which is involved mainly with locomotion. Muscle fibre size (measured as equivalent circle diameter) in the soleus muscle of the male Wistar rat increased from youth at 130 days(type 1 fibres, 61.2 μm;type 2, 58.3 μm) to middle age at 600 days (type 1 fibres, 70.4 μm; type 2, 68.0 μm) and then underwent atrophy in old age to 1,000 days (type 1 fibres, 54.5 μm; type 2, 38.0 μm). There was no growth or atrophy of these fibres in either hypophysectomized or food-restricted rats. There was an increased range of fibre sizes in control rats between youth and old age being 5-fold for type 1 fibres and 3-fold for type 2 fibres, but there was a loss of type 2 fibres in hypophysectomized rats. This ageing process in the range of fibre size was retarded by hypophysectomy (2-fold increase for type 1 fibres) and to a lesser extent by food restriction (3-fold increase for type 1 fibres). Muscle fibre atrophy and compensatory hypertrophy were not as prominent in the hypophysectomized and food-restricted groups as in the old control groups. In general these effects were similar to those previously shown for the gastrocnemius muscle. However, atrophy of both type 1 and type 2 fibres in old age was more pronounced in the soleus muscle. The retarded ageing of the soleus muscle in hypophysectomized and food-restricted rats was probably due to the absence or reduced circulating levels of hormones known to target muscle cells, such as growth hormone and thyroxine.

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Section: Hypophysectomy and Food Restriction Effectssupporting

confidence: 78%

Morphometric Analysis of the Muscle Fibres of the Soleus Muscle of the Ageing Rat: Long-Term Effect of Hypophysectomy and Food Restriction

Shorey

Everitt²,

Armstrong³

et al. 1993

Gerontology

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“…Interestingly, it was reported that the treatment of female rats with estradiol for 1 year attenuated the age-related increase in stiffening, glycoxidation, and permeability in carotid arteries (49). These findings suggest an inverse relationship between hormonal status and collagen cross-linking, a link suggested many years ago from the work of Everitt and associates using hypophysectomized rats (50,51).…”

Section: Table I Spearman Correlation Coefficients (R) Of Measured Skmentioning

confidence: 53%

Glucosepane Is a Major Protein Cross-link of the Senescent Human Extracellular Matrix

Sell

Biemel

Reihl

et al. 2005

Journal of Biological Chemistry

185

143

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The extracellular matrix in most tissues is characterized by progressive age-related stiffening and loss of proteolytic digestibility that are accelerated in diabetes and can be duplicated by the nonenzymatic reaction of reducing sugars and extracellular matrix proteins. However, most cross-links of the Maillard reaction described so far are present in quantities too low to account for these changes. Here we have determined in human skin and glomerular basement membrane (GBM) collagen the levels of the recently discovered lysinearginine cross-links derived from glucose, methylglyoxal, glyoxal, and 3-deoxyglucosone, i.e. glucosepane, MODIC, GODIC, and DOGDIC, respectively. Insoluble preparations of skin collagen (n ‫؍‬ 110) and glomerular basement membrane (GBM, n ‫؍‬ 28) were enzymatically digested, and levels were measured by isotope dilution technique using liquid chromatography/mass spectrometry. In skin, all cross-links increased with age (p < 0.0001) except DOGDIC (p ‫؍‬ 0.34). In nondiabetic controls, levels at 90 years were 2000, 30, and 15 pmol/mg for glucosepane, MODIC, and GODIC, respectively. Diabetes, but not renal failure, increased glucosepane to 5000 pmol/mg (p < 0.0001), and for all others, increased it to <60 pmol/mg (p < 0.01). In GBMs, glucosepane reached up to 500 pmol/mg of collagen and was increased in diabetes (p < 0.0001) but not old age. In conclusion, glucosepane is the single major cross-link of the senescent extracellular matrix discovered so far, accounting for up to >120 mole% of triple helical collagen modification in diabetes. Its presence in high quantities may contribute to a number of structural and cell matrix dysfunctions observed in aging and diabetes.Reducing sugars react nonenzymatically with proteins to form adducts and cross-links referred to as advanced glycation end products (1). Their accumulation is particularly high in long-lived proteins, such as lens crystallins and collagen, and results in intra-and intermolecular cross-linking. The latter has been hypothesized to result in an age-and diabetes-related stiffening of collagenous tissues and is believed to play an important role in the etiology of atherosclerosis and cardiovascular disease (3) as well as the loss of elasticity in lungs, joints, and skin (4 -6). These age-related processes are markedly accelerated by diabetes and are associated with morbidity and mortality in diabetic individuals (7,8). In skin, protein crosslinking is associated with an age-related loss of elasticity, increased stiffening, and wrinkling (9). However, this process occurs ubiquitously with age, suggesting a fundamental underlying mechanism.Although most of the age-related changes in the extracellular matrix could be duplicated by incubating reducing sugars with proteins, Eble et al. (10) suggested that the major cross-links are not stable to conventional conditions of acid hydrolysis. Indeed, Biemel et al. (11) recently showed that glucose and sugar-derived dicarbonyl intermediates react with human serum albumin to form various acid...

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“…Secondly, Peromyscus leucopus, which lives more than twice as long as Mus musctilus in the laboratory (Sacher & Hart, 1978), showed slower ageing of tendon fibre than Mus ; and several strains of laboratory rats differing in maximum longevity showed parallel differences in tendon fibre ageing (Bochantin & Mays, 1981). Finally, food restriction, a demonstrated age-retarding treatment of rodents (Weindruch & Walford, 1988), slows tendon fibre ageing (Everitt, Giles & Gal, 1969;, as do hormonal manipulations thought to retard senescence (Everitt, Wyndham & Barnard, 1983;Everitt & Meites, 1989).…”

Section: 'Ageing' Of Tail Tendon Fibresmentioning

confidence: 99%

Retarded senescence in an insular population of Virginia opossums (Didelphis virginiana)

1993

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Evolutionary senescence theory predicts that genetically isolated populations historically subjected to low rates of environmentally‐imposed mortality will ultimately evolve senescence that is retarded in relation to that of populations historically subjected to higher mortality rates. This prediction was evaluated in the field by comparing three general measures of senescence—age‐specific mortality rate acceleration, age‐related reproductive output and tail tendon collagen denaturation rate—in two radiocollared Virginia opossum (Didelphis virginiana) populations, one a mainland control and the other an insular population having a four‐to five‐thousand‐year history of reduced exposure to predators. In comparison with those on the mainland, insular female opossums were found to exhibit greater survivorship and reduced litter sizes at all ages, as well as slower acceleration of age‐specific mortality. Also, island females in their second reproductive year failed to show the senescent reduction in pouch young growth rate seen in mainland animals. Island opossums also manifested slower ‘ageing’ of tail tendon fibres, a generalized measure of physiological ageing. All these results are consistent with evolutionary senescence theory. Various environmental explanations (parasitism, disease, lessened food availability) for this populational difference are evaluated by physiological measures. No evidence for an environmental explanation is found.

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The anti-aging action of hypophysectomy in hypothalamic obese rats: Effects on collagen aging, age-associated proteinuria development and renal histopathology

Cited by 23 publications

References 23 publications

Morphometric Analysis of the Muscle Fibres of the Soleus Muscle of the Ageing Rat: Long-Term Effect of Hypophysectomy and Food Restriction

Morphometric Analysis of the Muscle Fibres of the Soleus Muscle of the Ageing Rat: Long-Term Effect of Hypophysectomy and Food Restriction

Glucosepane Is a Major Protein Cross-link of the Senescent Human Extracellular Matrix

Retarded senescence in an insular population of Virginia opossums (Didelphis virginiana)

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