20 research outputs found
Lipoprotein(a), apolipoprotein E genotype, and risk of Alzheimer's disease
No full textObjectives: To explore the possible role of serum lipoprotein(a) (Lp(a)), apolipoprotein E polymorphism, and total cholesterol (TC) serum concentrations in Alzheimer's disease (AD). Methods: Lp(a) serum concentrations, apolipoprotein E genotypes, and TC serum concentrations were determined in 61 patients with a diagnosis of probable AD and in 63 healthy unrelated age matched controls. Genomic DNA was obtained and amplified by polymerase chain reaction and apolipoprotein E genotypes were defined following a previously described procedure. Results: Lp(a) serum concentrations were significantly associated in a non-linear relation with an increased risk for AD, independently of apolipoprotein E genotypes and sex and dependent on age (truth association) and TC serum concentrations (spurious association). The effect of age adjusted for TC on the odds of having AD increased non-linearly with increasing Lp(a) serum concentrations, with a plateau between 70 and 355 mg/l (odds ratio 11.33). For Lp(a) serum concentrations ⥠360 mg/l, the effect of age (⥠72 years) was associated with a reduction in odds of having AD (odds ratio 0.15). Conclusion: It is suggested that increased Lp(a) serum concentrations, by increasing the risk for cerebrovascular disease, may have a role in determining clinical AD
The Potential of β-Hydroxy-β-Methylbutyrate as a New Strategy for the Management of Sarcopenia and Sarcopenic Obesity
No full textSarcopenia is defined as an age-related loss of skeletal muscle mass and function and is recognized as a major clinical problem for older people. Essential amino acid supplementation, particularly beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of leucine that is produced in skeletal muscle, has been evaluated in several studies as a nutritional approach to enhancing muscle protein synthesis in healthy or frail elderly subjects. Studies performed in in vitro conditions show that HMB may be effective in the treatment of muscle wasting, increasing myogenesis, reducing muscle apoptosis, and having a positive effect on muscle protein turnover; however, studies of the effects of HMB conducted in old animals have reported conflicting results. Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects. HMB supplementation results in an increase in skeletal muscle mass and strength in the elderly and its effect is even greater when combined with physical exercise. The role of HMB in sarcopenic obesity management is still under debate and a general lack of intervention studies in this population must be recognized. In conclusion, HMB appears to be effective for enhancing muscle mass and strength in the elderly. Less certain is the role of HMB supplementation in reducing fat mass and, thus, in the treatment of sarcopenic obesity
Possible role of S-adenosylmethionine, S-adenosylhomocysteine, and polyunsaturated fatty acids in predementia syndromes and Alzheimer's disease
No full textVery recent findings confirmed that S-adenosylmethionine (SAM) can exert a direct effect on glutathione S-transferase
(GST) activity. Alzheimer’s disease (AD) is accompanied by reduced GST activity, diminished SAM, and increased S-adenosyl
homocysteine (SAH), the downstream metabolic product resulting from SAM-mediated transmethylation reactions, when deprived
of folate. Therefore, these findings underscored the critical role of SAM in maintenance of neuronal health, suggesting a
possible role of SAM as a neuroprotective dietary supplement in AD. Given recent findings from clinical trials in which ω-3
polyunsturated fatty acids (PUFA) supplementation was effective only in very mild AD subgroups or mild cognitive impairment
(MCI), we suggest intervention trials using measures of dietary supplementation (dietary ω-3 PUFA and SAM plus B vitamin
supplementation) to determine if such supplements will reduce the risk for cognitive decline in very mild AD and MCI. Therefore,
key supplements are not necessarily working in isolation, and the most profound impact, or in some cases the only impact, is
noted very early in the course of AD, suggesting that nutriceutical supplements may bolster pharmacological approaches well
past the window where supplements can work on their own
Total cholesterol levels and the risk of mild cognitive impairment and Alzheimer's disease
No full textMolecular determinants of human longevity
No full textAging can be considered the product of an interaction between genetic, environmental, and lifestyle factors, which in turn influence longevity that varies between and within species. Given the high complexity of the phenomenon, several theories have been proposed providing an insight in the role of genetic and environmental factors in the process of aging. The "disposable soma theory", the most attractive theory, as well as other evolutionary theories state that aging is not only under genetic control and can also be considered a result of the failure of homeostasis. Therefore, although most studies agree that genetics influence longevity in humans, the magnitude of this effect is debated. A study on children of nonagenarians indicated a strong relationship between genetic influences and longevity, as did a study that compared the life span of adopted children with those of their adoptive and biological parents. Nonetheless, studies on twins reared together and twins reared apart indicated a small genetic influence on longevity. In fact, in one study, genetic factors explained no more than 30% of the variance in longevity, and in another study, this variance was even less. However, these studies did not analyze the oldest survivors, nor did they compare the longer-living with the shorter-living subjects. In fact, a strong relationship between genetics and longevity was demonstrated when centenarians were included, suggesting that genetic control of longevity is greatest in the oldest adults. A recent study demonstrated that the siblings of centenarians are three to four times more likely to survive to the 10th decade of life, compared with siblings of noncentenarians. Furthermore, immediate ancestors of Jeanne Calment from France, who died at the age of 123 years, were shown to be 10 times more likely to reach age 80 years than the ancestral cohort. These studies support the concept that longevity is a familial trait likely to be inherited and points to extreme age as the phenotype for an initial approach in identifying chromosomal regions that harbor longevity-assurance genes. Therefore, although the debate of the importance on genetics in determining the reaching of extreme longevity is open, it is mandatory to study the role of genetic determinants of longevity in humans, and several studies have been focused on healthy centenarians. In fact, these exceptionally long-living individuals represent a model-not discussed-of successful aging, having escaped the major age-associated diseases, and with most of them maintaining good cognitive and functional status. When age is plotted against the log of mortality rate, it gives a straight line as the mortality rate increases exponentially with age. However, the log of mortality rate falls below the expected at the ages of 95-100 years, indicating that mortality rate is no longer increasing exponentially in this age group. Although the mortality rate from cancers increases by approximately 10% per decade, it actually decreases after the age of 90 years. Thus, those individuals who have achieved an age of 90 years or older seem to be biologically unique; they have escaped disease-related mortality and get the biological make-up for successful aging. Interestingly, because the ratio of women to men at age 100 is 5 to 1, the female phenotype contributes to longevity independent of other genetic characteristics. Thus, based on biological distinctions, differences in mortality pattern, and the marked decrease in cancer, centenarians are likely to possess the strongest genetic determinants of longevity. The identification of gene variants involved in aging and longevity presents an interesting challenge. The discovery of genetic variations that explain even 5%-10% of the variation in survival to extreme old age could yield important clues about the cellular and biochemical mechanisms that affect the aging process and susceptibility to age-associated diseases. Candidate gene approaches, in which a gene is chosen based on function and the presumption that alteration in its function may affect the phenotype, have met with some success. Nonetheless, the definition of longevity and its associated intermediate phenotypes is still being debated. Furthermore, in the absence of detailed genealogies and prospective data, it is not possible to know definitively which individuals are or will be long-lived, and which are or will not be long-lived. Finally, individuals who died at early ages in accidents or war, or even from diseases resulting from environmental or other genetic factors, may still have harbored longevity-assurance genes. Recently, Richard Miller proposed a classification of longevity genes in different categories; the first one includes genes that cause or accelerate aging, even though it is a point of debate whether or not genetic mutations exist in nature that actually either cause or accelerate aging (e.g., P53 gene, telomerase gene). The second category concerns genes that increase the risk of a specific illness early in life but do not appear to be related to aging (e.g., CF gene and cystic fibrosis), or alternatively, genes that increase the risk of specific illness that resembles some of the consequences of aging. The third category consists of genes that influence or cause age-related diseases (e.g., Alzheimer disease [AD] and apolipoprotein E [APOE] ε{lunate}4 allele). Because variations in these genes are also associated with increased mortality risk, it is likely that centenarians do not have many of these predisposing variations. However, because the frequency of disease alleles is reduced in centenarians versus younger controls selected from the population, the statistical power of an association study between centenarians and subjects with a specific disease should be increased. This should be particularly true when searching for alleles that have a relatively high frequency in the general population. The fourth class includes low-fitness genes that extend maximum life span, probably by slowing down aging, as observed in lower organism mutations. One approach to determining the significance of such genes in humans is to screen for polymorphisms of their human homologs and to determine the allele frequencies among specific human phenotypes such as centenarians and to compare them to ethnically matched younger controls or controls predisposed to premature mortality. The fifth and sixth categories concern, respectively, polymorphic genetic loci that influence the rate of aging, and genes that influence differences in life span among species (e.g., longevity-enabling genes). A useful approach to finding these life span genes may be association studies using centenarian sibships. Families highly clustered for longevity, with five or more centenarian siblings and multiple centenarian cousins, provide the potential opportunity to perform linkage studies, linking the extreme longevity phenotype to a specific gene or genes. The aim of this chapter is to examine in depth the current knowledge of the role of different genetic determinants in modulating aging and in reaching of extreme longevity in humans, with particular interest in centenarian studies. We reviewed studies belonging to the third Miller's class of longevity genes, concerning those genes that influence or cause age-related diseases. First, we focused our attention on genes involved in vascular risk and vascular-related diseases and discussed the evidence that genetic factors, likely to be linked to both vascular disease and AD, may have an additional role in determining human longevity. Second, we reviewed principal findings on genetic factors linked to inflammation (interleukin 6 [IL-6] gene and other cytokine genes) and regulating immune response
An update on methods for sarcopenia diagnosis: from bench to bedside
No full textSarcopenia has been recognized as an age-related syndrome characterized by low muscle mass, low muscle strength, and low physical performance that is associated with increased likelihood of adverse outcomes including falls, fractures, hospitalization, frailty and mortality. Therefore, it is necessary to identify the condition early for applying intervention and prevention of the disastrous consequences of sarcopenia if left untreated. Clinical definition and diagnostic criteria for sarcopenia have been developed in the last years and different tools have been proposed for screening subjects with sarcopenia, evaluating the muscle mass, the muscle strength and the physical performance. In this review we analyzed the diagnostic criteria of sarcopenia and examined the current assessment tools used for the diagnosis and screening of sarcopenia
Coffee consumption habits and the risk of mild cognitive impairment: The Italian longitudinal study on aging
No full textCoffee, tea, or caffeine consumption may be protective against cognitive impairment and dementia. We estimated the association between change or constant habits in coffee consumption and the incidence of mild cognitive impairment (MCI). We evaluated 1,445 individuals recruited from 5,632 subjects, aged 65–84 year old, from the Italian Longitudinal Study on Aging, a population-based sample from eight Italian municipalities with a 3.5-year median follow-up. Cognitively normal older individuals who habitually consumed moderate amount of coffee (from 1 to 2 cups of coffee/day) had a lower rate of the incidence of MCI than those who never or rarely consumed coffee [1 cup/day: hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.211 to 1.02 or 1-2 cups/day: HR: 0.31 95% CI: 0.13 to 0.75]. For cognitively normal older subjects who changed their coffee consumption habits, those increasing coffee consumption (>1 cup of coffee/day) had higher rate of the incidence of MCI compared to those with constant habits (up to±1 cup of coffee/day) (HR: 1.80, 95% CI: 1.11 to 2.92) or those with reduced consumption (<1 cup of coffee/day) (HR: 2.17, 95% CI: 1.16 to 4.08). Finally, there was no significant association between subjects with higher levels of coffee consumption (>2 cups of coffee/day) and the incidence of MCI in comparison with those who never or rarely consumed coffee (HR: 0.26, 95% CI: 0.03 to 2.11). In conclusion, cognitively normal older individuals who increased their coffee consumption had a higher rate of developing MCI, while a constant in time moderate coffee consumption was associated to a reduced rate of the incidence of MC
Pulmonary pseudotumoral tuberculosis in an old man: A rare presentation
No full textThe pseudotumoral form of tuberculosis is very rare in healthy immunocompetent subjects and can simulates lung carcinoma causing diagnosis dilemma or lead to abusive surgical resection. Here we report a case of pulmonary tuberculosis in its pseudotumoral form in an immunocompetent old men who presented with cough, fatigue and fever. A computerized tomography of the chest indicated a dishomogeneous mass that compressed and deformed the left main bronchus that was referable to a primary tumor. The hystopatological exam from the bioptic samples obtained by bronchoscopy was negative for neoplasia. Moreover, an abdomen CT scan showed hypodense solid lesions of the liver likely to be considered as metastasis; the histological analysis of these hepatic lesions was negative for neoplasia. It was necessary to perform a second CT scan of the chest and another bronchoscopy with biopsy and histopathological examination before establishing the diagnosis of the pulmonary pseudotumoral form. The case report confirm, as previously described, the difficulties in the diagnosis of this rare form of tuberculosis that lead to a delay in therapy, and suggest that the pseudotumor has to be included as different diagnosis of pulmonary mass also in healthy immunocompetent subjects.</jats:p
