New Regenerative and Anti-Aging Medicine Approach Based on Single-Stranded Alpha-1 Collagen for Neo-Collagenesis Induction: Clinical and Instrumental Experience of a New Injective Polycomponent Formulation for Dermal Regeneration.

This study explores the efficacy of a novel polycomponent formulation (KARISMA Rh Collagen® FACE, Taumedika Srl, Rome, Italy), containing 200 mg/mL of non-crosslinked high-molecular-weight hyaluronic acid (HMW-HA), 200 µg/mL of a human recombinant polypeptide of collagen-1 alpha chain, and 40 mg/mL of carboxymethyl cellulose (CMC) as a regenerative medicine for skin regeneration and rejuvenation. This formulation combines non-crosslinked high-molecular-weight hyaluronic acid, human recombinant polypeptide of collagen-1 alpha chain, and carboxymethyl cellulose to stimulate collagen type I production and enhance skin hydration. This study involved 100 subjects with varying skin conditions, divided into three groups based on skin aging, smoking history, and facial scarring, to evaluate the product's effectiveness in skin regeneration and aesthetic improvement. The methodology included two injections of Karisma (2 mL for each injection) one month apart, with evaluations conducted using FACE-Q questionnaires, the SGAIS Questionnaire, and Antera 3D skin scanner measurements at baseline, 30 days, and 60 days post-treatment. The results demonstrated a significant reduction in skin roughness and an improvement in skin quality across all the groups, with no correlation between the outcomes and the patient's age. The subjective assessments also indicated high satisfaction with the treatment's aesthetic results. The analyzed data allow us to conclude that the single-stranded collagen with hyaluronic acid and carboxymethyl-cellulose formulation is able to stimulate the skin's regenerative response, yielding significant results both in vitro and, through our study, also in vivo. This new polycomponent formulation effectively stimulates skin regeneration, improving skin quality and texture, with significant aesthetic benefits perceived by patients, and a low incidence of adverse events, marking a promising advancement in regenerative medicine.

Antiviral, virucidal and antioxidant properties of Artemisia annua against SARS-CoV-2.

Natural products are a rich source of bioactive molecules that have potential pharmacotherapeutic applications. In this study, we focused on Artemisia annua (A. annua) and its enriched extracts which were biologically evaluated in vitro as virucidal, antiviral, and antioxidant agents, with a potential application against the COVID-19 infection. The crude extract showed virucidal, antiviral and antioxidant effects in concentrations that did not affect cell viability. Scopoletin, arteannuin B and artemisinic acid (single fractions isolated from A. annua) exerted a considerable virucidal and antiviral effect in vitro starting from a concentration of 50 µg/mL. Data from Surface Plasmon Resonance (SPR) showed that the inhibition of the viral infection was due to the interaction of these compounds with the 3CLpro and Spike proteins of SARS-CoV-2, suggesting that the main interaction of compounds may interfere with the viral pathways during the insertion and the replication process. The present study suggests that natural extract of A. annua and its components could have a key role as antioxidants and antiviral agents and support the fight against SARS-CoV-2 variants and other possible emerging Coronaviruses.

The Role of Consumption of Molybdenum Biofortified Crops in Bone Homeostasis and Healthy Aging.

Osteoporosis is a chronic disease and public health issue in aging populations. Inadequate intake of micronutrients increases the risk of bone loss during an adult's lifespan and therefore of osteoporosis. The aim of the study was to analyze the effects of consumption of biofortified crops with the micronutrient molybdenum (Mo) on bone remodeling and metabolism in a population of adults and seniors. The trial enrolled 42 senior and 42 adult people randomly divided into three groups that consumed lettuce biofortified with molybdenum (Mo-biofortified group) or without biofortification (control group) or molybdenum in a tablet (Mo-tablet group) for 12 days. We chose an experimental period of 12 days because the bone remodeling marker levels are influenced in the short term. Therefore, a period of 12 days allows us to determine if there are changes in the indicators. Blood samples, obtained at time zero and at the end of the study, were compared within the groups adults and seniors for the markers of bone resorption, C-terminal telopeptide (CTX) and bone formation osteocalcin, along with the markers of bone metabolism, parathyroid hormone (PTH), calcitonin, albumin-adjusted calcium, vitamin D, phosphate and potassium. Consumption of a Mo tablet did not affect bone metabolism in the study. Consumption of Mo-biofortified lettuce significantly reduced levels of CTX and PTH and increased vitamin D in adults and seniors while levels of osteocalcin, calcitonin, calcium, potassium and phosphate were not affected. The study opens up new considerations about the role of nutrition and supplementation in the prevention of chronic diseases in middle-aged and older adults. Consumption of Mo-biofortified lettuce positively impacts bone metabolism in middle-aged and older adults through reduced bone resorption and improved bone metabolism while supplementation of Mo tablets did not affect bone remodeling or metabolism. Therefore, Mo-biofortified lettuce may be used as a nutrition intervention to improve bone homeostasis and prevent the occurrence of osteoporosis in the elderly.

Boosting plant food polyphenol concentration by saline eustress as supplement strategies for the prevention of metabolic syndrome: an example of randomized interventional trial in the adult population.

Introduction: Phenolic compounds in lettuce can increase by the application of positive stress (eustress) such as moderate saline stress. Phenolic compounds possess antioxidant capacity that is a key factor in the detoxification of excess reactive oxygen species. A double-blinded randomized interventional and placebo- controlled study design was carried out to compare the effect of daily dietary eustress lettuce ingestion in hepatic, lipid, bone, glucose, and iron metabolism. Methods: Forty-two healthy volunteers, 19 female and 23 male participants, were divided into two groups. Participants were randomized into a polyphenol-enriched treatment (PET) arm or control arm. Each arm consumed 100 g/day of control or eustress (polyphenols enriched treatment = PET) lettuce for 12 days. Primary study outcomes were serological analysis for assessing hepatic, lipid, bone, iron, and glucose markers at baseline and after 12 days. Secondary outcomes assessed body composition. Results: Salinity stress reduced plant yield but increased caffeic acid (+467%), chlorogenic acid (+320%), quercetin (+538%), and rutin (+1,095%) concentrations. The intake of PET lettuce reduced PTH, low-density lipoprotein (LDL), cholesterol, alanine transaminase (ALT), and aspartate transaminase (AST) enzyme levels and increased vitamin D and phosphate levels, while iron and glucose metabolism were unaffected. Discussion: Supplementation with eustress lettuce by increasing polyphenols concentration ameliorates hepatic, lipid, and bone homeostasis. Body composition was not affected. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT06002672, identifier: NCT06002672.

From Small Peptides to Large Proteins against Alzheimer'sDisease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly. The two cardinal neuropathological hallmarks of AD are the senile plaques, which are extracellular deposits mainly constituted by beta-amyloids, and neurofibrillary tangles formed by abnormally phosphorylated Tau (p-Tau) located in the cytoplasm of neurons. Although the research has made relevant progress in the management of the disease, the treatment is still lacking. Only symptomatic medications exist for the disease, and, in the meantime, laboratories worldwide are investigating disease-modifying treatments for AD. In the present review, results centered on the use of peptides of different sizes involved in AD are presented.

Effects of a Resistance Training Protocol on Physical Performance, Body Composition, Bone Metabolism, and Systemic Homeostasis in Patients Diagnosed with Parkinson's Disease: A Pilot Study.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments and it is correlated with loss of bone mineral density. This study aimed to analyze the effects of resistance training on bone metabolism, systemic homeostasis, body composition, and physical performance in people with PD. Thirteen subjects (age 64.83 ± 5.70) with PD diagnosis were recruited. Participants performed neuromuscular tests, body composition assessment, and blood sample analysis at baseline, and after an 11 weeks-training period. Each training session lasted 90 min, three times a week. The participants had significant improvements in the timed up and go (p < 0.01), sit to stand (p < 0.01), dominant peg-board (p < 0.05), dominant foot-reaction time (p < 0.01), and functional reach tests (p < 0.05). They showed better pressure foot distributions in the left forefoot (p < 0.05) and hindfoot (p < 0.05) and increased cervical right lateral bending angle (p < 0.05). The protocol affects bone metabolism markers osteocalcin (p < 0.05), calcium (p < 0.01), PTH (p < 0.01), the C-terminal telopeptide (CTX) (p < 0.01), and vitamin D (p < 0.05). Eleven weeks of resistance training improved manual dexterity, static and dynamic balance, reaction time, cervical ROM, and reduced bone loss in people with PD.

Dare to jump: The effect of the new high impact activity SuperJump on bone remodeling. A new tool to maintain fitness during COVID-19 home confinement.

SuperJump is a high impact activity performed on an elastic trampoline that mixes aerobic and anaerobic exercises already proposed as home-based activity for preventing a sedentary lifestyle. We determined in a randomized controlled trial whether 20 weeks of SuperJump activity would promote bone formation and reduce resorption in eumenorrheic women. Twenty-four women were randomized to a non-exercise group (control group) or an exercise group that performed SuperJump activity three times a week for 20 weeks. Blood samples were collected in both groups at baseline and at the end of the 20 weeks and compared within and between the groups for C-terminal telopeptide (CTX), a marker of bone resorption, osteocalcin, a marker of bone formation, and the markers of bone metabolism parathyroid hormone (PTH), calcitonin, albumin-adjusted calcium (Aa calcium), vitamin D, phosphate and potassium. After 20 weeks of SuperJump activity, levels of CTX were significantly reduced while levels of osteocalcin were increased. PTH, calcium and potassium were involved in the mechanism of action because PTH was reduced while calcium and potassium were increased. Calcitonin, vitamin D and phosphate levels did not change. These data suggest that SuperJump activity is able to reduce bone resorption and improve bone formation by acting on essential regulators of bone metabolism. They also suggest that SuperJump training may be used as a valuable intervention to prevent the occurrence of osteoporosis in aging because it improves bone homeostasis in favor of bone formation and could counteract a sedentary lifestyle, such as during COVID-19 home confinement, which could itself contribute to the variation of bone metabolism. Trial registration: Clinicaltrials.gov NCT04942691 -retrospectively registered.

Plasma proteome profiling of healthy individuals across the life span in a Sicilian cohort with long-lived individuals.

The study of healthy human aging is important for shedding light on the molecular mechanisms behind aging to promote well-being and to possibly predict and/or avoid the development of age-related disorders such as atherosclerosis and diabetes. Herein, we have employed an untargeted mass spectrometry-based approach to study age-related protein changes in a healthy Sicilian plasma cohort including long-lived individuals. This approach confirmed some of the previously known proteins correlated with age including fibulin-1, dystroglycan, and gamma-glutamyl hydrolase. Furthermore, our findings include novel proteins that correlate with age and/or with location and uric acid, which could represent a unique signature for healthy aging.

A New Potential Dietary Approach to Supply Micronutrients to Physically Active People through Consumption of Biofortified Vegetables.

Micronutrients are required in many reactions involved in physical activity and exercise. Most physically active people do not meet the body's needs in terms of micronutrients through diet. The novelty of the present manuscript is the use of an innovative dietary approach to supply micronutrients to physically active people through biofortified food. Therefore, the key point of this study was to verify whether supplementation with biofortified vegetables-and specifically molybdenum (Mo)-enriched lettuce-in healthy volunteers affects essential regulators of body homeostasis and, specifically, hematological parameters, iron and lipid metabolism, and hepatic function. Twenty-four healthy volunteers were allocated in a double-blinded manner to either a control group that consumed lettuce, or the intervention group, which consumed Mo-enriched lettuce, for 12 days. Blood samples were collected at baseline (T0) and after 12 days (T1). We found that supplementation with Mo-enriched lettuce did not affect hematological parameters, liver function, or lipid metabolism, but significantly improved iron homeostasis by increasing non-binding hemoglobin iron by about 37% and transferrin saturation by about 42%, while proteins of iron metabolism (e.g., transferrin, ferritin, ceruloplasmin) were not affected. The serum molybdenum concentration increased by about 42%. In conclusion, this study shows that consumption of Mo-biofortified lettuce ameliorates iron homeostasis in healthy subjects, and suggests that it could be used as a new nutritional supplementation strategy to avoid iron deficiency in physically active people.

Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study.

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study.

It is estimated that one-third of the world's population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcome via dietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food - Full-Text View - ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health.

Is the Secret in the Gut? SuperJump Activity Improves Bone Remodeling and Glucose Homeostasis by GLP-1 and GIP Peptides in Eumenorrheic Women.

We showed that twenty weeks of SuperJump activity, an innovative workout training performed on an elastic minitrampoline, reduced bone resorption and increased bone formation in eumenorrheic women acting on the key points of the regulation of bone metabolism. The present study analyzed whether the gastrointestinal hormones are involved in the mechanism of action and if it has an impact on glucose homeostasis. The control group was composed of twelve women, similar to the exercise group that performed SuperJump activity for twenty weeks. The analysis was performed on blood samples and investigated GLP-1, GIP, GLP-2, PYY, ghrelin, glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity. The results showed that the activity contributes to raising the GLP-1and GIP levels, and not on GLP-2, PYY, and ghrelin, which did not change. Moreover, SuperJump activity significantly reduced fasting insulin, glucose, insulin resistance, and increased insulin sensitivity but did not affect beta cell function. These data suggest that GLP-1, and GIP are involved in the mechanism of action that improves bone and glucose homeostasis following 20 weeks of SuperJump activity in eumenorrheic women.

Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles. Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity.

1,2,4-Oxadiazole is a heterocycle with wide reactivity and many useful applications. The reactive O-N bond is usually reduced using molecular hydrogen to obtain amidine derivatives. NH4CO2H-Pd/C is here demonstrated as a new system for the O-N reduction, allowing us to obtain differently substituted acylamidine, acylguanidine and diacylguanidine derivatives. The proposed system is also effective for the achievement of a reductive rearrangement of 5-(2'-aminophenyl)-1,2,4-oxadiazoles into 1-alkylquinazolin-4(1H)-ones. The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics.

Age and Gender-related Variations of Molecular and Phenotypic Parameters in A Cohort of Sicilian Population: from Young to Centenarians.

People are living longer, but lifespan increase does not coincide with a boost in health-span. Thus, improving the quality of life of older people is a priority. Centenarians reach extreme longevity in a relatively good health status, escaping or delaying fatal or strongly invalidating diseases. Therefore, studying processes involved in longevity is important to explain the biological mechanisms of health and well-being, since knowledge born from this approach can provide valuable information on how to slow aging. We performed the present study in a well characterized very homogeneous sample of 173 people from Western Sicily, to update existing literature on some phenotypic aspects of aging and longevity and to propose a range of values for older people. We classified 5 age groups, from young adults to centenarians, to understand the age and gender-related variations of the different parameters under study. We collected anamnestic data and performed anthropometric, bioimpedance, molecular, haematological, oxidative, and hematochemical tests, adopting a multidimensional analysis approach. An important evidence of the present study is that there are differences related to both age and gender in several biomarkers. Indeed, gender differences seem to be still poorly considered and inadequately investigated in aging as well as in other medical studies. Moreover, we often observed comparable parameters between young and centenarians rather than non-agenarians and centenarians, hypothesizing a sort of slowdown, almost followed by a reversal trend, in the decay of systemic deterioration. The study of centenarians provides important indications on how to slow aging, with benefits for those who are more vulnerable to disease and disability. The identification of the factors that predispose to a long and healthy life is of enormous interest for translational medicine in an aging world.

The Impact of Diet and Physical Activity on Bone Health in Children and Adolescents.

There is growing recognition of the role of diet and physical activity in modulating bone mineral density, bone mineral content, and remodeling, which in turn can impact bone health later in life. Adequate nutrient composition could influence bone health and help to maximize peak bone mass. Therefore, children's nutrition may have lifelong consequences. Also, physical activity, adequate in volume or intensity, may have positive consequences on bone mineral content and density and may preserve bone loss in adulthood. Most of the literature that exists for children, about diet and physical activity on bone health, has been translated from studies conducted in adults. Thus, there are still many unanswered questions about what type of diet and physical activity may positively influence skeletal development. This review focuses on bone requirements in terms of nutrients and physical activity in childhood and adolescence to promote bone health. It explores the contemporary scientific literature that analyzes the impact of diet together with the typology and timing of physical activity that could be more appropriate depending on whether they are children and adolescents to assure an optimal skeleton formation. A description of the role of parathyroid hormone (PTH) and gut hormones (gastric inhibitory peptide (GIP), glucagon-like peptide (GLP)-1, and GLP-2) as potential candidates in this interaction to promote bone health is also presented.

Post-Acute COVID-19 Neurological Syndrome: A New Medical Challenge.

In December 2019, in Wuhan (China), a highly pathogenic coronavirus, named SARS-CoV-2, dramatically emerged. This new virus, which causes severe pneumonia, is rapidly spreading around the world, hence it provoked the COVID-19 pandemic. This emergency launched by SARS-CoV-2 also had, and still has, devastating socio-economic aspects. Assessing the impact of COVID-19 on vulnerable groups of people is crucial for the adaptation of governments' responses. Growing scientific evidence suggests that it is essential to keep the attention on people after acute SARS-CoV-2 infection; indeed, some clinical manifestations are frequently present even after recovery. There is consensus on the need to define which symptoms persist after the infection and which disabilities may arise after COVID-19. Recent reviews, case reports, and original contributions suggest that various organs may be affected, and neurological symptoms are present in about one third of patients with COVID-19. Neurological complications after severe COVID-19 infection might include delirium, brain inflammation, stroke, and nerve damage. In the recent pandemic, neurologists and neurobiologists have a chance to study key features of infection neurology. Furthermore, the psychological impact of the pandemic should not be underestimated, although there is currently no definition for this condition.

Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains.

Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer's disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3ß compared to healthy controls suggesting an impairment of metabolism in the AD patient's brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment.

Proeryptotic Activity of 4-Hydroxynonenal: A New Potential Physiopathological Role for Lipid Peroxidation Products.

BACKGROUND: Eryptosis is a physiological, apoptosis-like death of injured erythrocytes crucial to prevent premature haemolysis and the pathological sequalae generated by cell-free haemoglobin. When dysregulated, the process is associated to several inflammatory-based pathologies. 4-Hydroxy-trans-2-nonenal (HNE) is an endogenous signalling molecule at physiological levels and, at higher concentrations, is involved in the pathogenesis of several inflammatory-based diseases. This work evaluated whether HNE could induce eryptosis in human erythrocytes. METHODS: Measurements of phosphatidylserine, cell volume, intracellular oxidants, Ca++, glutathione, ICAM-1, and ceramide were assessed by flow cytometry. Scanning electron microscopy evaluated morphological alterations of erythrocytes. Western blotting assessed caspases. PGE2 was measured by ELISA. Adhesion of erythrocytes on endothelial cells was evaluated by gravity adherence assay. RESULTS: HNE in the concentration range between 10-100 µM induces eryptosis, morphological alterations correlated to caspase-3 activation, and increased Ca++ levels. The process is not mediated by redox-dependent mechanisms; rather, it strongly depends on PGE2 and ceramide. Interestingly, HNE induces significant increase of erythrocytes adhesion to endothelial cells (ECs) that are in turn dysfunctionated as evident by overexpression of ICAM-1. CONCLUSIONS: Our results unveil a new physiopathological role for HNE, provide mechanistic details of the HNE-induced eryptosis, and suggest a novel mechanism through which HNE could exert pro-inflammatory effects.

The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs).

Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: the first group with subjects less than 40 years old, the second group ranging from 40 to 64 years old, the third group ranging from 65 to 89 years old, the fourth group ranging from 90 to 94 years old, and the fifth group with subjects more than 95 years old. A relationship was observed between LLIs and MMP-2, but not between LLIs and MMP-9. However, in the LLI group, MMP-2 and MMP-9 values were significantly correlated. Furthermore, in LLIs, we found a positive correlation of MMP-2 with the antioxidant catabolite uric acid and a negative correlation with the inflammatory marker C-reactive protein. Finally, in LLIs MMP-9 values correlated directly both with cholesterol and with low-density lipoproteins. On the whole, our data suggest that the observed increase of MMP-2 in LLIs might play a positive role in the attainment of longevity. This is the first study that shows that serum activity of MMP-2 is increased in LLIs as compared to younger subjects. As far as we are concerned, it is difficult to make wide-ranging conclusions/assumptions based on these observations in view of the relatively small sample size of LLIs. However, this is an important starting point. Larger-scale future studies will be required to clarify these findings including the link with other systemic inflammatory and antioxidant markers.