Mitoresilience: Hormesis, Psycho-physical Resilience, Mitochondria and Heart Rate Variability as Relevant Interplaying Elements in Longevity Medicine.

Psycho-biological resilience is considered one of the most important factors in the epigenetics of aging. Cell senescence exhibits a series of possible biochemical derangements concerning mitochondria, proteasome, genome and membranes. Research has shown that resilience can be acquired through hormesis, a set of conservative and adaptive processes based on biphasic doseresponse to specific mild stressors, such as fasting, intake of polyphenols, exercising, physical and chemical stress and mental engagement. These stimuli were shown to elicit beneficial cellular metabolic pathways, such as sirtuin activation, mechanistic target of rapamycin and insulin growth factor- 1 downregulation, nuclear related factor 2 upregulation and autophagy. The complex of these resilience-building processes plays a documented role in longevity. Mitochondria are regarded as one of the core actors of aging processes and represent the main target of hormetic approaches [mitohormesis]; furthermore, the influence of the mind on mitochondria, and thus on the balance of health and disease has been recently established, leading to the so-called mitochondria psychobiology. Hence, psychologic and physical stress that reflects on these organelles may be regarded as a relevant factor in cell senescence, and thus the proposed "mitoresilience" denomination may be pertinent within the biomedical science of aging. Finally, the quantification of individual resilience is becoming increasingly important in aging science, and the investigation of the autonomic nervous system through heart rate variability (HRV) proved to be a valid method to quantify this parameter. In conclusion, an integrated approach targeting hormetic pathways to improve psychophysical resilience (namely mitoresilience), supported by the monitoring of HRV, may represent a valuable option in longevity medicine.

Short-term effects of a maqui-based nutraceutical on heart rate variability, psycho-physical resilience and on a few metabolic biomarkers: a randomized controlled study.

OBJECTIVES: To assess the immediate/short-term outcomes of a maqui berry-based nutraceutical (MBN) supplementation on the autonomic nervous system (ANS), resilience level, metabolism and body composition. METHODS: A randomized controlled single-blind study was performed on healthy subjects. Throughout 30 days, one group took 1,000 mg/day of an MBN (Maqui 500®), the control group had no supplementation. On day 0 (T0) and 30 (T3) all subjects performed blood tests, bioimpedance spectroscopy and questionnaires for resilience, perceived stress and short-form 12 (SF12). At T0, 75' after T0 (T1), on day 7 and at T3 the subjects underwent biometric parameter measurement and heart rate variability (HRV) test to investigate psycho-physical resilience. RESULTS: Fifteen subjects per group were included; abnormal seasonal high temperatures altered individuals' lifestyle and nutrition, influencing the trial's outcomes. Biometric parameters, blood pressure, oxygen saturation and blood tests did not differ between T0 and T3 in both groups. In the MBN group the HRV analysis showed a significant increase of ANS coordination (p=0.05), parasympathetic activity at 75', very low frequencies and total power at T3, whereas these parameters decreased in the control group. SF12 mental score improved in the maqui group (p=0.02); the questionnaire-based outcomes showed no further variations. In the control subjects bioimpedance showed an increase of resistance and fat mass, with decreased total body water and lean mass (p=n.s.). CONCLUSIONS: The maqui-based nutraceutical improved HRV, namely ANS activation/coordination, and SF12 mental component. Blood tests and bioimpedance/biometric parameters mildly varied. The elapsed hot weather likely biased many investigated variables.

Bioimpedance spectroscopy and volumetry in the immediate/short-term monitoring of intensive complex decongestive treatment of lymphedema.

AIMS: To assess (a) immediate/short-term outcomes of intensive complex decongestive treatment of lower limb lymphedema, by means of bioimpedance spectroscopy and tape measurement-based volumetry, and (b) correlation between these two methods. PATIENTS AND METHODS: Cohort study on patients affected by unilateral primary or secondary lymphedema, stage II or III. Patients underwent complex decongestive treatment (manual and electro-sound lymphatic drainage, compression bandage, exercises, low-carb nutrition, and dietary supplements) for six days. Before (D0), three and six days after complex decongestive treatment (D3 and D6), volumetry and bioimpedance spectroscopy data of the total limb and lower leg were collected. Statistical analysis was applied to pre-post treatment outcomes and to the volumetry/bioimpedance spectroscopy correlation. RESULTS: Forty-one patients (15 males and 26 females, mean age: 50.7 years) were included. A progressive improvement of volumetry and bioimpedance spectroscopy figures was recorded. Total limb and leg volumetry (mean value in cc) was, respectively, 11,072.9 and 3150.8 at D0, 10,493 (-5.2%, p = 0.001) and 2980.2 (-5.4%, p < 0.001) at D6. Total limb lymphatic index at D0 and D6 was 18.9 and 14.8 (-21.5%, p < 0.001). Total limb resistance at D0, D3, and D6 was 200.4, 225.7, and 237.5 (+18.5%, p < 0.001), respectively; leg resistance at D0 and D6 was 117.5 and 150 (+27.7%, p < 0.001), respectively. Total limb reactance at D0, D3, and D6 was 12.2, 15, and 16.6 (+35.5%, p < 0.001), respectively. Leg reactance at D0 and D6 was 7.7 and 11.5 (+ 49.6%, p < 0001), respectively. Correlation volumetry/bioimpedance spectroscopy data were (a) total limb volumetry/resistance rho = -0.449, p < 0.01; volumetry/reactance rho=-0.466, p < 0.01; volumetry/lymphatic index rho = 0.581, p < 0.01; (b) leg volumetry/resistance rho=-0.579, p < 0.01; volumetry/reactance rho=-0.469, p < 0.01; volumetry/lymphatic index rho = 0.466, p < 0.05. CONCLUSIONS: Complex decongestive treatment on lymphedematous limbs was effective at short term; both volumetry and bioimpedance spectroscopy showed a statistically significant improvement. Resistance and reactance increase, with lymphatic index decrease, correlated with volumetry decrease. Bioimpedance spectroscopy proved to help to assess fluid decrease and the tissue-related parameters variations.

Lymphology and translational medicine.

Lymphology is evolving in search of a better management of lymphedema patients, both as to the diagnostic pathway and as to the therapeutic options. Similarly, lymphatic system is involved in a wide spectrum of pathophysiologic processes of most chronic degenerative diseases. Translational medicine integrates the interdisciplinary scientific knowledge to improve diagnostic and therapeutic options in the biomedical field. Inflammation and lymphatic function are regarded as the connecting biochemical factors in most diseases. This review focuses on the scientific publications regarding lymphatic system in connection to psycho-neuroendocrine immunology, hormesis, epigenetics and more generally nutrition and lifestyle. The interaction between lymphology and translational medicine may play a relevant role to improve management of lymphedema on the one hand, and of chronic degenerative diseases on the other.

Aging in the Perspective of Integrative Medicine, Psychoneuroendocrineimmunology and Hormesis.

Aging has been considered a progressive decrease of a living organism's homeodynamics, which indicates a reduction of psycho-biological resilience. This narrative review provides an overview of the available literature related to the holistic approach of integrative medicine, Psychoneuroendocrineimmunology (PNEI) and hormesis in the aging process. On the basis of Pathophysiology of cell senescence and of chronic degenerative diseases, possible preventive/therapeutic pathways have been examined. Chronic low grade cellular inflammation and chronic stress have been shown as the general interlinked factors inducing aging, on the basis of complex biochemical, cell and multi-organ derangements. The main cell degenerative processes which have been related to aging are: altered mitochondria DNA/metabolism, excessive oxidative stress, glycation, alteration of autophagy and proteasome, and genome alterations. Literature about longevity-targeting interventions, beyond conventional medicine, describes a spectrum of possible measures to improve psycho-biological resilience, based on the PNEI paradigm, on hormesis and upon mitochondriatargeted interventions. Calorie restriction, exercising, fasting, nutraceuticals, sleep regulation, specific breathing, meditation and psychotherapy are discussed, among others.

Randomized, Placebo-controlled Study of a Nutraceutical Based on Hyaluronic Acid, L-carnosine, and Methylsulfonylmethane in Facial Skin Aesthetics and Well-being.

Objective: The purpose of this study was to evaluate the efficacy and safety of a multicomponent nutraceutical (MCN) on facial skin. Methods: A randomized, placebo-controlled, single-blind trial was conducted involving two groups of female subjects affected by facial skin photoaging. For two months, volunteers took a daily dose of MCN containing 200mg of hyaluronic acid, 500mg of L-carnosine, and 400mg of methylsulfonylmethane, or a placebo. At Day 0 (T0) and Day 60 (T60), face skin hydration, elasticity, and sebometry were measured with an instrumental skin tester, and digital images of facial wrinkles were scored. A subject-based quali-/ quantitative assessment evaluating satisfaction/ quality of life was performed at T60. Results: The MCN and placebo groups each included 25 volunteers (mean ages: 49.3 and 47.8 years, respectively). After 60 days of MCN intake, glabella skin hydration and elasticity improved by 15.2 percent and 22.6 percent, respectively (p=0.03; p=0.004), glabella sebaceous secretion decreased by 24.2 percent (p=0.01), skin hydration and elasticity of the periocular area increased by 12.6 percent and 15.9 percent, respectively, and skin hydration and elasticity of the oral commissural area increased by 17.6 percent and 16 percent, respectively (p<0.001). No significant variation occurred in the placebo group. Wrinkle depth improved slightly in the MCN group (p=0.043 in the periocular area) but not in the placebo group. A slight improvement in joint pain and mucosae/ hair appearance was reported in the questionnaire in the MCN group only. Conclusions: Our results suggest that MCN is safe and effective for facial skin aesthetics and well-being.

Compression with 23 mmHg or 35 mmHg stockings after saphenous catheter foam sclerotherapy and phlebectomy of varicose veins: A randomized controlled study.

OBJECTIVES: To compare two different medical compression stockings after varicose vein treatment. PATIENTS AND METHODS: A randomized single-blind controlled study on two compression regimes after saphenous catheter foam sclerotherapy + phlebectomy was performed. After pads and 5 mmHg contention sock, 23 mmHg (group A, Struva 23®) or 35 mmHg (group B, Struva 35®) medical compression stocking was applied 24 h/day for seven days; subsequently 21-23 mmHg medical compression stocking in daytime. Symptoms, compliance, skin findings, and bioimpedance spectroscopy parameters were assessed. RESULTS: A total of 94 patients (48 and 49 limbs in groups A and B, respectively) were enrolled. Three (T3) and seven (T7) days post-operatively, most symptoms were significantly milder in group B, especially pain and heaviness at T7 and at day 40 (T40). Ambulation, medical compression stocking stability/tolerability and skin healing were significantly better in group B, with p = 0.046, 0.021/0.060, and 0.010, respectively, at T7. Bioimpedance parameters increased at T7 and decreased at T40 in both groups; leg reactance and limb L-Dex improved in group B at T7 and T40, respectively (p = 0.039 and 0.012). CONCLUSIONS: Compression with 23 and 35 mmHg medical compression stocking after catheter foam sclerotherapy + phlebectomy was effective and well tolerated at immediate/short term. Compression with 35 mmHg medical compression stocking provided less adverse post-operative symptoms and better tissue healing. Bioimpedance results confirmed a slightly better edema improvement with 35 mmHg medical compression stocking.

A Polyphenol-Based Multicomponent Nutraceutical in Dysmetabolism and Oxidative Stress: Results from a Pilot Study.

To assess short-term efficacy and safety of a multicomponent nutraceutical (MCN) on dysmetabolism and oxidative stress, a pilot prospective observational study was performed on 21 individuals (12 men and 9 women) who took, for 60 days, 2 tablets per day of an MCN based on antioxidants and metabolism regulators: hydroxytyrosol (15 mg), maqui (300 mg), amla (200 mg), monacolin K (10 mg), berberine (245 mg), astaxanthin (0.5 mg), coenzyme Q10 (100 mg), and folic acid (200 mcg). On day 0 (T0) and day 60 (T60), all participants underwent laboratory tests related to lipid profile, carbohydrate metabolism, oxidative stress, and cellular inflammation. Statistical analysis was applied to the resulting data. A significant improvement of most atherogenesis and oxidative stress biomarkers was recorded (mean figure at T0 and T60, p value): total cholesterol 243.50/194.83 mg/dl, p =.0002; low-density lipoproteins 174.50/124.58 mg/dl, p =.0001; glycemia 96.25/88.50 mg/dl, p =.035; total free radicals 306.44/280.93 U.Carr., p =.036; serum antioxidant capacity 2103.00/2246.06 umol/l, p =.0042; oxidized cholesterol 680.33/597.25 uEq/l, p =.0511. Insulinemia, microalbuminuria, high-density lipoproteins, C-reactive protein, and triglycerides had no statistically significant variation. Body weight and systo-diastolic pressure showed no significant change from T0 to T60. No relevant side effects were reported. The investigated MCN (Eonlipid), based on polyphenols, significantly improved the oxidative stress parameters and decreased the majority of atherogenesis parameters at short term. No significant side effects were reported. Further placebo-controlled studies should possibly corroborate the promising results of this pilot study.