Marco Malavolta

Publications (98) View all

• Article: Effects of human Toll-like receptor 1 polymorphisms on ageing.

  Peter Uciechowski, Eva Maria Oellig, Erminia Mariani, Marco Malavolta, Eugenio Mocchegiani, Lothar Rink
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  ABSTRACT: BACKGROUND: Advanced age results in crucial alterations of the innate and adaptive immune system leading to functional defects resulting in infection and chronic diseases. Toll-like receptors (TLR) recognize pathogenic structures and are important in the immune response to infections and vaccination. However, the role of TLR single nucleotide polymorphisms (SNP) is poorly understood in the setting of human ageing. This study investigated the impact of the TLR1 SNPs A743G and T1805G on ageing in different age groups from two European populations. RESULTS: The TLR1 genotypes 743AA/1805GG (TLR1neg) are associated with a TLR1 negative phenotype, impaired function and susceptibility to tuberculosis. Carriers of heterozygous 743AG/1805TG and homozygous 743GG/1805TT genotypes (TLR1pos) have a TLR1 positive phenotype. By comparing healthy young and old German donors, the old group showed a tendency to carry more TLR1neg and less homozygous TLR1pos genotypes. Anti-inflammatory Interleukin (IL)-1 receptor antagonist (Ra) was significantly elevated in supernatants of mononuclear cells from old German subjects with a TLR1pos genotype in contrast to those with the 743AA genotype. Healthy old individuals and nonagenarians from Italy displayed significantly higher frequencies of TLR1pos genotypes than the old group from Germany. The data show that tumor-necrosis-factor (TNF)alpha, CXCL8 and CCL2 levels were higher in old donors from Germany than plasma levels from old Italian donors. TNFalpha and CCL2 levels were significantly raised in old German individuals compared to Italian nonagenarians. German and Italian donors with the TLR1neg genotype basically produced more CCL2 than older European donors with TLR1pos genotypes. CONCLUSION: The higher frequency of the TLR1pos genotype in elderly Italian subjects may result from different ethnic populations. Lower inflammatory mediator release of aged Italian individuals is probably due to different background in nutrition, diet, genetics and to psychological aspects. Elderly donors carrying TLR1pos genotypes basically release more anti-inflammatory IL-1Ra and less inflammatory CCL2 suggesting a decline of the pro-inflammatory status found in ageing and, therefore, this may define an anti-inflammatory phenotype. Future studies are needed to elucidate the association of a TLRpos genotype with decreased susceptibility to infections and reduced risk to develop artherosclerosis.
  Immunity & Ageing 02/2013; 10(1):4.
• Article: Peripheral mononuclear cell rejuvenation for senescence surveillance in Alzheimer disease.

  Marco Malavolta, Andrea Basso, Francesco Piacenza, Laura Costarelli, Robertina Giacconi, Eugenio Mocchegiani
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  ABSTRACT: Recent observations have pointed out that microglia, astrocytes and cerebrovascular endothelial cells senescence might contribute to the onset or progression of sporadic AD. The accumulation of senescent dysfunctional microglia or senescence related changes of other cells within CNS could be causally implicated in AD and age-related dysfunction and their efficient removal could represent a pivotal mechanism to prevent or delay neurodegeneration. The question how senescent cells are cleared from CNS has been poorly investigated, even though it is reasonable to believe that resident microglia is involved in this task. However, accumulating evidence now support the idea that assistance by peripheral mononuclear phagocytes (MP) in AD could be essential to control local brain inflammation and remove Abeta depots. Based on the current knowledge it is reasonable to hypothesize that senescence surveillance might be among the tasks that blood derived MP are called to envelop in the CNS during particular conditions, especially in the case senescent microglia is not able to achieve this task properly. However, age-related dysfunctions of these players of innate immunity could lead to depict a series of events that synergically with microglia and other CNS cells senescence could lead to a rapid progression of the disease. Hence, the design of intervention aimed at targeting accumulating senescent cells by rejuvenation of peripheral MP function seems an attractive tool that perhaps would also help to clarify the processes involved in senescence surveillance in normal and AD brain.
  Current pharmaceutical design 10/2012; · 4.41 Impact Factor
• Article: Metallothioneins, Ageing and Cellular Senescence: A Future Therapeutic Target.

  Eugenio Mocchegiani, Laura Costarelli, Andrea Basso, Robertina Giacconi, Francesco Piacenza, Marco Malavolta
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  ABSTRACT: In ageing, the accumulation of damaged molecules provoked by oxidative stress and inflammation contributes to altered gene expressions and cellular dysfunction. The antioxidant system is crucial in order to prevent damage to intracellular molecules including DNA and, consequently, to avoid cellular dysfunction or neoplastic transformation. However, during serious DNA damage, the cells can activate a response characterized by cell cycle arrest and production of factors (mainly chemokines and cytokines) named "senescent associated secretory phenotype" (SASP) with the putative function to attract immune cells involved in the clearance of the senescent cells. This phenomenon named "cellular senescence" is, by one side, an important tumor suppressive mechanism but, on the other side, it contributes to impair tissue regenerative capacity and to possible transformation of neighbouring cells to cancer cells if a rapid clearance of the senescent cell doesn't occur. Therefore, preventing DNA damage via an optimal intracellular antioxidant defence is the key to reduce risk of cancer while keeping senescent changes at minimum. Zinc-bound Metallothioneins (MT), could play a key role in this prevention because they are antioxidant proteins and release zinc ions for several proteins and enzymes involved in antioxidant and DNA-repair responses. Reduced MT expression and intracellular zinc occur in some models of senescent cells. This process is of relevance since zinc ions released from MT could be implicated in the modulation of SASP. In chronic inflammation, such as in ageing, the dysfunction in zinc release from MT occurs, suggesting a potential contribution to the onset of senescent cells. Hence, MT could be directly or indirectly involved in the modulation of cellular senescent state and might represent a possible therapeutic target against the accumulation of dysfunctional senescent cells.
  Current pharmaceutical design 10/2012; · 4.41 Impact Factor
• Article: BMI, life-style and psychological conditions in a sample of elderly italian men and women

  Fiorella Marcellini, C. Giuli, R. Papa, C. Gagliardi, M. Malavolta, E. Mocchegiani
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  ABSTRACT: ObjectivesTo identify the relationship among cognitive status, psychological conditions, anthropometric measurements and life-style in a sample of elderly Italian men and women. MethodsThree hundred and six volunteers for ZINCAGE Project recruited. The sample was made up of healthy older adults living in the Marche Region aged 65 and over. All elderly were given a complete medical, anthropometric assessment, and psycho-social evaluation. ResultsOverall, the participants perceived themselves to be in very good or good (22%) or fair (69%) health; only 9% reported a poor health status. The 46% of the sample fell within the normal body mass index (BMI) range, though 38% were overweight, 12% were obese, and only 4% were underweight. In both sexes, BMI significantly decreased with age (p<0.001). BMI was positively associated with performing sedentary activities (r = 0.188; p < 0.001). Levels of both sedentary (r = 0.221; p < 0.001) and non-sedentary (r = 0.258; p < 0.001) leisure activities were positively associated with education level (p<0.05). It was found that lower scores of physical activity were associated to higher scores of Geriatric Depression Scale (r=−0.425; p<0.01), lower scores of Mini Mental State Examination (r=0.266; p<0.001) and higher score of Perceived Stress Scale (r=−0.131; p<0.05). ConclusionMen and women lead different lifestyles and have a different psychological status, with advancing age consequently stressing the need for healthy lifestyle programmes particularly in the case of overweight and obese elderly people. Key wordsLifestyle-ageing-anthropometric status-ZINCAGE project
  The Journal of Nutrition Health and Aging 04/2012; 14(7):515-522. · 2.69 Impact Factor
• Article: BMI, life-style and psychological conditions in a sample of elderly Italian men and women.

  F Marcellini, C Giuli, R Papa, C Gagliardi, M Malavolta, E Mocchegiani
  [show abstract] [hide abstract]
  ABSTRACT: To identify the relationship among cognitive status, psychological conditions, anthropometric measurements and life-style in a sample of elderly Italian men and women. Three hundred and six volunteers for ZINCAGE Project recruited. The sample was made up of healthy older adults living in the Marche Region aged 65 and over. All elderly were given a complete medical, anthropometric assessment, and psycho-social evaluation. Overall, the participants perceived themselves to be in very good or good (22%) or fair (69%) health; only 9% reported a poor health status. The 46% of the sample fell within the normal body mass index (BMI) range, though 38% were overweight, 12% were obese, and only 4% were underweight. In both sexes, BMI significantly decreased with age (p<0.001). BMI was positively associated with performing sedentary activities (r=0.188; p<0.001). Levels of both sedentary (r=0.221; p<0.001) and non-sedentary (r=0.258; p<0.001) leisure activities were positively associated with education level (p<0.05). It was found that lower scores of physical activity were associated to higher scores of Geriatric Depression Scale (r=-0.425; p<0.01), lower scores of Mini Mental State Examination (r=0.266; p<0.001) and higher score of Perceived Stress Scale (r=-0.131; p<0.05). Men and women lead different lifestyles and have a different psychological status, with advancing age consequently stressing the need for healthy lifestyle programmes particularly in the case of overweight and obese elderly people.
  The Journal of Nutrition Health and Aging 08/2010; 14(7):515-22. · 2.69 Impact Factor