Thymic Hormone Deficiency in Normal Ageing and Down's Syndrome: Is There a Primary Failure of the Thymus?

Fabris, Ν.; Amadio, L.; Licastro, Federico; Mocchegiani, Eugenio; Zannotti, Maria; Franceschi, Claudio

doi:10.1016/s0140-6736(84)92325-0

Cited by 153 publications

(81 citation statements)

References 18 publications

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“…Children with DS showed several sign of impaired immunity and activation of peripheral inflammation [34].…”

Section: Down Syndrome (Ds) and Chronic Inflammationmentioning

confidence: 99%

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Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Licastro¹,

Porcellini²

2017

Down Syndr Chr Abnorm

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IntroductionAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Prevalence and incidence of this type of dementia is increasing and extensive research has focused on AD pathogenetic mechanisms to find effective preventive procedures and therapeutic drugs. However, no therapy is available. Therefore, focusing upon diverse aspects of the disease in order to discover new therapeutic strategies appears to be relevant for patients. Moreover, new approaches to the disease's pathogenesis may open innovative prevention opportunities for the elderly or other groups of people without manifest cognitive alterations, but with increased risk of developing dementia.Brain amyloid deposits and intra neuronal neurofibrillary tangles (NFTs) have been suggested as inducers of the disease [1,2]. However, these neuropathological alterations are often also present in the brain of elderly without cognitive alterations or AD pathology [3]. Therefore, it is uncertain whether amyloid or other proteinaceous brain depositions might be causatively linked to AD.The biological role of the amyloid precursor protein (APP) and its proteolytic derivatives (A-beta peptide) in normal brain is still uncertain [4]. However, recent data showed that A-beta peptide is an anti-microbial factor [5]. A recent study reported that the A-beta peptide showed an in vitro anti-virus activity [6]. Therefore, A-beta peptides may play multiple roles in human brain and contribute to antimicroorganism responses.As we elsewhere discussed, genetic data from four genome wide association (GWA) studies on AD [7][8][9] suggested that persistent virus infections may be potentially associated with the age related cognitive decline. In fact, this specific genetic signature may predispose to AD by affecting the individual susceptibility to virus infections [7] during the age associated decline of immune competence. Adults with Down's syndrome (DS) o trisomy of chromosome 21show an elevated risk of cognitive decline and dementia with advancing age. The over expression of the APP gene on the chromosome 21 may lead to an early amyloid deposition in DS brains and be a susceptibility factor for AD [10].Middle age people with DS also show increased tangle brain deposition, neuronal loss and neuro-inflammation along with cerebrovascular pathology [10]. All these factors might accelerate brain aging in DS. A dramatic increase in life expectancy, coupled with a significant reduction in early mortality, has led to a substantial increment in the number of DS subjects reaching old age. This demographic picture parallels increased incidence and prevalence of the age related degenerative diseases in persons with DS.Chronic inflammation is associated with the pathogenesis of most chronic degenerative diseases. In fact, a relevant inflammatory component is always associated with AD, autoimmune diseases, diabetes, atherosclerosis, sarcopenia and cancer. It is of interest that increased levels of circulating inflammatory mediators may be secondary to impaired cytokine resp...

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“…Children with DS showed several sign of impaired immunity and activation of peripheral inflammation [34].…”

Section: Down Syndrome (Ds) and Chronic Inflammationmentioning

confidence: 99%

“…Both natural and adaptive immunity show a variable degree of alterations in DS [34] and infections are more frequent in children with the syndrome [35].…”

Section: Down Syndrome (Ds) and Chronic Inflammationmentioning

confidence: 99%

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Licastro¹,

Porcellini²

2017

Down Syndr Chr Abnorm

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“…The measure of the thymulin activity in the plasma before treatment (No-FMilk) is included in the normal range for the age of the subjects herein considered (0.5-1.5 ng/ml) (Fabris et al 1984). The treatment with zincfortified milk is able to induce a significant increment (33.34 %) of the thymulin activity when compared to No-FMilk (1.52±0.07 vs 1.14±0.07 ng/ml, respectively) (p<0.05).…”

Section: Thymulin Activitymentioning

confidence: 99%

Effects of zinc-fortified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study

Costarelli

Giacconi

Malavolta

et al. 2014

AGE

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Zinc is a relevant nutritional factor for the whole life of an organism because it affects the inflammatory/immune response and antioxidant activity, leading to a healthy state. Despite its important function, the dietary intake of zinc is inadequate in elderly. Possible interventions include food fortification because it does not require changes in dietary patterns, the cost is low and it can reach a large portion of the elderly population, including very old subjects. Studies evaluating the impact of Zn-fortified foods on functional parameters in elderly, in particular, in very old individuals, are missing. The objective of this study was to evaluate the efficacy of consumption of a zinc-fortified drinking skim milk (Zn-FMilk) for a period of 2 months in comparison to standard non-fortified milk (No-FMilk) on some biochemical parameters, zinc status, inflammatory/immune response and on a key parameter of the T cell-mediated immunity (thymulin hormone) in healthy very old subjects. The treatment with zinc-fortified milk (Zn-FMilk) is a good omen to increase the cell-mediated immunity in very old age represented by thymulin activity and some cytokine (IL-12p70, IFN-γ) release. At clinical level, a good healthy state occurs in 70 % of the subjects with no hospitalization after 1 year of the follow-up in comparison to very old control subjects that did not participate to crossover design. In conclusion, the Zn-FMilk can be considered a good functional food for elderly, including older people. It might be a good replacement to the zinc tablets or lozenges taking into account the attitude of old people to uptake milk as a preferential food.

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“…Zinc supplementation trials have been justified mainly because of reports of relatively low serum zinc in DS. Of 16 studies which have compared serum levels of zinc in individuals with DS and individuals without DS, 13 showed significantly reduced zinc concentrations in individuals with DS [42][43][44][45][46][47][48][49][50][51][52][53][54] , while three found no significant difference [55][56][57] . We found only one randomised controlled trial of zinc in DS 58 .…”

Section: Zinc Supplementationmentioning

confidence: 99%

“…Fabris and colleagues 44 reported that adding zinc to the serum of individuals with DS increased their serum thymic factor (FTS) to levels normally seen in individuals without DS and also reduced the concentration of FTS inhibitory factor. Chiricolo and coworkers 59 showed that individuals with DS who were supplemented for 4 months with 1 mg of zinc/kg/day had an increase in the in vitro incorporation of thymidine into their phytohaemagglutinin (PHA) stimulated lymphocytes similar to individuals without DS.…”

Section: Zinc Supplementationmentioning

confidence: 99%

Nutritional supplementation in Down syndrome: theoretical considerations and current status

Ani

Grantham‐McGregor

Muller

2000

Develop Med Child Neuro

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Thymic Hormone Deficiency in Normal Ageing and Down's Syndrome: Is There a Primary Failure of the Thymus?

Cited by 153 publications

References 18 publications

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Effects of zinc-fortified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study

Nutritional supplementation in Down syndrome: theoretical considerations and current status

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