Effects of Livagen and Epitalon, New Peptide Bioregulators, on Enkephalin-Degrading Enzymes from Human Serum

The effects of new peptide bioregulators—Livagen (Lys-Glu-Asp-Ala) and Epitalon (Ala-Glu-Asp-Gly)—on the endogenous opioid system was studied. In particular, attention was focused on their ability to change the activity of enkephalin-degrading enzymes of blood serum and interact with opioid receptors of the brain membrane fraction. Enkephalinase activity was assayed in vitro by the rate of ³H-Leu-enkephalin hydrolysis in the presence of Livagen and Epitalon. These peptides inhibited enkephalin-degrading enzymes of human serum. Livagen proved to be more efficient than some well-known peptidase inhibitors, such as puromycin, leupeptin, and D-PAM. The dose–inhibitory effect curves for Livagen and Epitalon were plotted; their IC₅₀ equaled 20 and 500 M, respectively. The interaction between the peptides and opioid receptors was estimated using a radioreceptor method with [³H][D-Ala², D-Leu⁵]-enkephalin. No interaction was observed between the peptides and - or -opioid receptors of the membrane fraction from the rat brain.     

Sex and age specificity of susceptibility genes modulating survival at old age

OBJECTIVE: We aimed to investigate the influence of the genetic variability of candidate genes on survival at old age in good health. METHODS: First, on the basis of a synthetic survival curve constructed using historic mortality data taken from the Italian population from 1890 onward, we defined three age classes ranging from 18 to 106 years. Second, we assembled a multinomial logistic regression model to evaluate the effect of dichotomous variables (genotypes) on the probability to be assigned to a specific category (age class). Third, we applied the regression model to a cross-sectional dataset (10 genes; 972 subjects selected for healthy status) categorized according to age and sex. RESULTS: We found that genetic factors influence survival at advanced age in good health in a sex- and age-specific way. Furthermore, we found that genetic variability plays a stronger role in males than in females and that, in both genders, its impact is especially important at very old ages. CONCLUSIONS: The analyses presented here underline the age-specific effect of the gene network in modulating survival at advanced age in good health.     

Obesity history as a predictor of walking limitation at old age

Objective: To study whether walking limitation at old age is determined by obesity history. Research Methods and Procedures: In a retrospective longitudinal study based on a representative sample of the Finnish population of 55 years and older (2055 women and 1337 men), maximal walking speed, body mass, and body height were measured in a health examination. Walking limitation was defined as walking speed <1.2 m/s or difficulty in walking 0.5 km. Recalled height at 20 years of age and recalled weight at 20, 30, 40, and 50 years of age were recorded. Results: Subjects who had been obese at the age of 30, 40, or 50 years had almost a 4‐fold higher risk of walking limitation compared to non‐obese. Obesity duration increased the age‐ and gender‐adjusted risk of walking limitation among those who had been obese since the age of 50 (odds ratio, 4.33; 95% confidence interval, 2.59 to 7.23, n = 114), among the obese since the age of 40 [6.01 (2.55 to 14.14), n = 39], and among the obese since the age of 30 [8.97 (3.06 to 26.29), n = 14]. The risk remained elevated even among those who had previously been obese but lost weight during their midlife or late adulthood [3.15 (1.63 to 6.11), n = 71]. Discussion: Early onset of obesity and obesity duration increased the risk of walking limitation, and the effect was only partially mediated through current BMI and higher risk of obesity‐related diseases. Preventing excess weight gain throughout one's life course is an important goal in order to promote good health and functioning in older age.     

Satellite cell regulation of muscle mass is altered at old age.

Muscle mass is decreased with advancing age, likely due to altered regulation of muscle fiber size. This study was designed to investigate cellular mechanisms contributing to this process. Analysis of male Fischer 344 X Brown Norway rats at 6, 20, and 32 mo of age demonstrated that, even though significant atrophy had occurred in soleus muscle by old age, myofiber nuclear number did not change, resulting in a decreased myonuclear domain. Also, the number of centrally located nuclei was significantly elevated in soleus muscle of 32-mo-old rats, correlating with an increase in gene expression of MyoD and myogenin. Whereas total 5'-bromo-2'deoxyuridine (BrdU)-positive nuclei were decreased at older ages, BrdU-positive myofiber nuclei were increased. These results suggest that, with age, loss of muscle mass is accompanied by increased myofiber nuclear density that involves fusion of proliferative satellite cells, resembling ongoing regeneration. Interestingly, centrally located myofiber nuclei were not BrdU labeled. Rats were subjected to hindlimb suspension (HS) for 7 or 14 days and intermittent reloading during HS for 1 h each day (IR) to investigate how aging affects the response of soleus muscle to disuse and an atrophy-reducing intervention. After 14 days of HS, soleus muscle size was decreased to a similar extent at all three ages. However, myofiber nuclear number and the total number of BrdU-positive nuclei decreased with HS only in the young rats. IR was associated with an attenuation of atrophy in soleus muscles of 6- and 20- but not 32-mo-old rats. Furthermore, IR was associated with an increase in BrdU-positive myofiber nuclei only in young rats. These data indicate that altered satellite cell function with age contributes to the impaired response of soleus muscle to an intervention that attenuates muscle atrophy in young animals during imposed disuse.     

Latent mitochondrial DNA deletion mutations drive muscle fiber loss at old age

With age, somatically derived mitochondrial DNA (mtDNA) deletion mutations arise in many tissues and species. In skeletal muscle, deletion mutations clonally accumulate along the length of individual fibers. At high intrafiber abundances, these mutations disrupt individual cell respiration and are linked to the activation of apoptosis, intrafiber atrophy, breakage, and necrosis, contributing to fiber loss. This sequence of molecular and cellular events suggests a putative mechanism for the permanent loss of muscle fibers with age. To test whether mtDNA deletion mutation accumulation is a significant contributor to the fiber loss observed in aging muscle, we pharmacologically induced deletion mutation accumulation. We observed a 1200% increase in mtDNA deletion mutation‐containing electron transport chain‐deficient muscle fibers, an 18% decrease in muscle fiber number and 22% worsening of muscle mass loss. These data affirm the hypothesized role for mtDNA deletion mutation in the etiology of muscle fiber loss at old age.     

Peptide hydra morphogen activates Na/H-exchange in human erythrocytes

The effect of peptide morphogen of hydra (PMH) on Na+/H+ exchange in human erythrocytes was studied. It was shown that this peptide leads to 2-7 fold activation of the rate of protons efflux from the human erythrocytes at concentration 100 nM. It was assumed, that peptide controls and regulates proliferation via the activation Na+/H+ exchange.     

Addressing the age-old question of old age

A report on the Second International Conference on Functional Genomics of Ageing, Hersonissos, Greece, 28 April-1 May 2004.     

Demystifying the age of old olive trees

Iconic to the Mediterranean landscape, the age of monumental olive trees with large trunks and unique silhouettes is often considered several centuries to millennia. Here we combine tree-ring and radiocarbon dating to show that most monumental olive trees may have maximum ages between 300 and 500 years. Our example helps disentangling the tree size-longevity conundrum in a major Mediterranean cultivated tree species and important cultural heritage.