PROGETTO A.A. - Fondazione Friuli

Personalized Health Management of Physical, Mental and Social Frailty in the Elderly



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Cell senescence is a permanent and irreversible cell cycle arrest that is accompanied by changes in cell morphology and physiology. Senescence evolved as a beneficial response to damage promoting wound healing, limiting fibrosis, fighting against cancer and helping embryonic development. However, excessive accumulation of senescent cells is considered to favour aging-related diseases and other changes associated with ageing and is an emerging hallmark of cancer chemoresistance. Therefore, it is highly demanded the design of strategies to selectively eliminate senescent cells and improve the health condition of ageing population.
Senolytic therapy is an emerging strategy to promote senescent cells replacement, currently in clinical trial for age-related diseases, such as sarcopenia, but represent a promising perspective for designing novel anticancer strategies to combine with current chemotherapy regimens. Different compounds have been indicated to exert senolytic capacity. Among them, some polyphenols are indicated as promising in regulating cell senescence, aging, and longevity. As well known, polyphenols represent a large class of compounds naturally occurring in many fruits and vegetables and derived products. They are divided into several classes including flavonoid and non-flavonoid compounds and exist as aglycones and sugar conjugates. Examples of polyphenols under study for senolytic effect are quercetin, curcumin, resveratrol and oleuropein.
The aim of this WP will be to i) tackle ageing related issues by studying the molecular mechanisms of ageing and related molecular biomarkers; ii) define anti-ageing strategies by exploiting the senolytic activity of bioactive molecules; iii) develop foods for elderly; iv) organize dissemination activities to get population aware of the basis of ageing processes.

Involved researchers of DAME and DI4A
1. Enrico Braidot
2. Sonia Calligaris
3. Alessandro Cavarape
4. Monica Colitti
5. Clara Comuzzi
6. Alessandra Corazza
7. Francesco Curcio
8. Rossella De Marco
9. Gianluigi Gigli
10. Nadia Innocente
11. Giovanna Lippe
12. Renata Lonigro
13. Ugolino Livi
14. Francesca Patriarca
15. Maria Rosa Peri
16. Nicoletta Pellegrini
17. Sandro Spanga
18. Mara Lucia Stecchini
19. Bruno Stefanon
20. Paolo Strazzolini
21. Gianluca Tell
22. Emilio Tibaldi
23. Francesca Tulli
24. Giancarlo Verardo
25. Marco ZancanI
26. Giulia Antoniali
27. Marta Codrich
28. Kristel Conte
29. Giuseppe Dall’Agnese
30. Monica Degrassi
31. Renato Fanin
32. Matilde Clarissa Malfatti
33. Giovanna Mangiapane
34. Sofia Melchior
35. Martina Moretton
36. Tommaso Montanari

In WP2 the following activities will be organized:
1 A parish map
2 An international seminar on medical anthropological approach on ageing and active ageing

WP2.1 A parish map
A “parish map” (for the Italian experience, “mappe di comunità”), as a collaborative, interactive, and intergenerational tools will be co-produced both by youngs and older people living in the same place will be produced.
The map construction will be an innovative process during which the tangible and intangible heritage of a local context will be redefined and co-experienced by the social actors through different type of communication: visual, graphic, oral and written language. The role of ageing peoples is basic in the process, as guardians of the community memories; at the same time youngs’ perspective will be essential to in order to understand and manage the future changes of their place.
The aim of the action is to contribute to social interaction and the maintaining of a good memory in older people, through exercising and sharing their “semantic memory” (defining as “our knowledge” of the world around us).

Involved researchers
1. Linda Borean
2. Nadia Carestiato
3. Michele Geronazzo
4. Marina Marcolini
5. Patrizia Quattrocchi

WP2.2 An international seminar on medical anthropological approach on ageing and active ageing
The seminar will focus on the contribution of medical anthropology to the topic of aging and active aging. Theoretical perspectives, research experiences, methodologies and case studies will be presented and discussed with experts, health practitioners, students and stakeholders.
The seminar will make available a comprehensive, comparative and social actors-based approach to integrate the biomedical and healthcare perspectives and contribute to the groundbreaking “Frailty prevention approach to these issues. It will also contribute to create and enhance international and national research networks on the topic.
Involved researchers
Patrizia Quattrocchi
Donatella Cozzi

Specific educational and recreational projects and activities can demonstrably improve the general wellbeing of the elderly, their smart and active ageing, and ultimately their community inclusion within a multicultural and multilingual society. The analysis of the literary conceptualisations and representations of old age and the elderly of different epochs and cultures can contribute valuable insights into stereotypes and clichés which make up our own cultural construct of old age.
WP 3 Researchers:
Fusco (DILL); D. Zoletto (DILL); D. Cozzi (DILL); guest speakers
Luise (DILL); A. Bier (research assistant DILL); M. Cohen (president of the ‘L-Senior’ association
Paolone (DILL); guest speakers
Di Sciacca (DILL); D. Capelli (PhD student DILL); guest speaker.

Work ability tends to decline with age but a fair cooperation between the employer and the employee can create a better balance in the workplace and enhance work ability. Risk assessments should take into consideration the large individual differences in functional capacities and health of personnel, age, disabilities, gender issues.
Age is just one aspect of the diversity of the workforce, but the awareness of managers and supervisors of age-related issues needs to be improved.
All these age-related actions and improvements needed at workplaces can be termed “age management”.
WP 4 – Involved Researchers (DISG)
1. Valeria Filì (PO)
2. Marina Brollo (PO)
3. Elisabetta Bergamini (PA)
4. Rocco Lobianco (PA)
5. Anna Zilli (PA)
6. Francesco Bilotta (RU)
7. Raffaella Pasquili (RU)
8. Carmela Garofalo (PhD, Assegnista)
9. Claudia Carchio (PhD, Assegnista)
10. Caterina Mazzanti (Borsista)
11. Gianluca Picco (PhD Student)
12. Gianluigi Pezzini (PhD Student)
13. Carla Ida Maggio (PhD, Assegnista)
14. Massimiliano De Falco (Assegnista)
15. Luigi Gaudino (PA)
16. Gioietta Maccioni (RU)

Fabio Buttussi (RU)

Frailty represents a challenging expression of population ageing, which can be defined as a condition of vulnerability, a consequence of the cumulative decline in multiple physiological systems over a lifespan. Landmark literature has focused on the association between models for frailty and adverse health outcomes. Besides, population ageing brings a wide set of health challenges, such as the common chronic conditions associated with aging and of the required coordination between healthcare staff, family members, and caregivers to take care for the elderly. Moreover, it deserves attention the WHO recommendation on the shifting from disease-driven attention towards personalized and integrated continuous care of older individuals aimed at the maintenance of functional independence. These represent emerging issues in the care of elderly well-being and in the reduction of sources of frailty in older adults, which is sustained by the improvement of health and quality of life among elders.
Aging adults experience higher risk of chronic diseases (heart disease, cancer, chronic bronchitis or emphysema, stroke, diabetes mellitus, dementia, Alzheimer’s disease) reducing their health status. Health status is one of the most important indicators of well-being and predicts a large proportion of societal expenditures on health and social services devoted to elderly. The increased availability of specific types of health and social environmental data has enhanced the set of quantitative tools useful to assess health policy and planning measures for elderly populations. Moreover, the identification of the trajectories of health measures adopted is relevant to forecasting health care needs. Finally, the data required to study the health status and well-being of the elderly may come from many sources in order to detect the different quality of life aspects eligible to cause frailty in older adults. On these grounds, the following tasks will be developed. 
WP 5 Involved researchers:
1. Laura Rizzi (DIES)
2. Laura Pagani (DIES)
3. Luca Grassetti (DIES)
4. Alessio Fornasin (DIES
5. Stefano Comino (DIES)
6. Alvisa Palese (DAME)
7. Alessandro Cavarape (DAME)
8. Michele Gobbato (ARCS – FVG)
9. Ivana Burba (ARCS – FVG)
10. Elena Clagnan (ARCS – FVG)
11. Stefano Lazzer (DAME)
12. Stefano Burigat (DMIF)

Sarcopenia is a syndrome characterized by a progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death.
Low muscle strength is the most reliable measure of muscle function.  Clinically, sarcopenia is diagnosed by a loss of muscle strength, reflecting the presence of reduced quantity and quality of skeletal muscle mass. However, presence of both low muscle function (strength) and low muscle mass is essential for the diagnosis of sarcopenia. The assessment of muscle quantity/mass can be estimated by a variety of techniques not suitable in routine clinical practice (Magnetic Resonance Imaging, Computed Tomography). DEXA is also used for measuring skeletal muscle mass. However, DEXA is currently not usable for use in community and can also be influenced by the hydration status of the patient.  
Ultrasound is a widely used technique to measure muscle mass and also to assess muscle quality. Moreover it could be applied bedside. Ultrasound can detect a decrease in muscle thickness and in cross-sectional area of muscles (quadriceps) within a relatively short period of time, thus suggesting potential for use of this tool in clinical practice, including use in the community.  Thus, ultrasound has the advantage of being able to assess both muscle quantity and quality, and can be considered a potential reliable tool in clinical practice for the diagnosis and in the screening of sarcopenia in elderly subjects.
Since sarcopenia is a condition that can be prevented or treated if diagnosed in time, this diagnostic technique could be of support in the diagnosis at bedside or when gold standard techniques are not available.
In this project we will perform on a population of elderly subjects both ultrasound investigation of the quadriceps femoral muscle and DEXA.  We will compare the measurements obtained with the two methods in order to validate ultrasonography as a novel method of diagnosis and screening of sarcopenia in our clinical center.
The possibility of analyzing the obtained data with image analysis and artificial intelligence methods will be evaluated.
Apart from the loss of muscle mass and strength, sarcopenia is also associated with metabolic impairments. Of specific interest are the impairments of oxidative metabolism, the main energy source for activities lasting longer than 1-2 minutes, and thereby strictly associated with everyday life. The resulting reduction of exercise tolerance negatively affects the patients’ quality of life, leads to inactivity/sedentarism, insulin resistance, glucose intolerance, and is a risk factor for cardiovascular and other chronic diseases, including cancer. Our group has a long experience in the analysis of “central” (respiratory and cardiovascular) and “peripheral” (peripheral vascular, endothelial function, intramuscular matching between O2 delivery and O2 uptake, peripheral O2 diffusion, intramuscular oxidative metabolism and mitochondrial function and dysfunction) impairments of oxidative metabolism. Among peripheral factors, mitochondrial dysfunction (including impaired respiratory function, ROS production, increased susceptibility to permeability transition) leads to redox imbalance and insulin resistance. Identification and quantification of biomarkers associated with these impairments, in the elderly population, will allow to define the metabolic impact of sarcopenia, and to envisage rehabilitation interventions.
WP6  - Involved researchers:
1. Alessandro Cavarape (DAME)
2. Chiara Zuiani (DAME)
3. Vincenzo Della Mea (DMIF)
4. Christian Di Luccio (Resident MD - DAME)
5. Bruno Grassi (DAME)
6. Giovanna Lippe (DI4A)
7. Marina Comelli (DAME)
8. Luigi Vetrugno (DAME)
9. Lucrezia Zuccarelli (Assegnista – DAME)
10. Giovanni Baldassarre (PhD student – DAME)
11. Clarissa Gissi (PhD student – DAME)

Endometrial carcinoma is the most frequent neoplastic pathology of the female genital system and is the fifth most frequent cause of cancer in women. In 2019, in the 50-69 age group, it was in third place for frequency of cancer.
Oxidative stress represents an important link between endometrial cancer, obesity and diabetes. The damage resulting from oxidative stress has been implicated in the physiological processes of aging and in the pathogenesis of various diseases. The relationship between oxidative stress and endometrial cancer is an emerging theme. The aim of the study is to evaluate the level of oxidative stress in patients with endometrial cancer at diagnosis with particular reference to risk factors such as diabetes and obesity in order to evaluate the changes following treatment and during follow up, paving the way in the future to the role of oxidative stress reduction through lifestyle modification and the use of oxidizing substances in the prevention of endometrial carcinoma and a procession of chronic diseases associated with aging. The number of elderly patients in Western countries is increasing, as is their life expectancy. At the same time, surgical indications have been extended to elderly patients with gynaecologic cancer patients. surgery in elderly patients is particularly challenging because of the possible presence of one or more serious chronic diseases. For this reason, the management of these patients require a close collaboration within a multidisciplinary team consisting of geriatric, anesthesia, and gynaecologic specialists. For elderly cancer patients with a high risk of developing postoperative complications, the use of minimally invasive surgery (MIS) is particularly interesting, because the reduced surgical trauma can potentially lead to a reduction in postoperative complications. Robotic surgery (RS) is gaining increasing acceptance for treating gynaecologic cancer, allowing performance of more complex procedures by MIS. The exact role of this promising technology and surgical strategy in gynaecologic oncology for elderly patients remains under investigation. We were prompted to investigate the feasibility, safety and short-term outcomes of RS versus laparoscopy for elderly patients affected by endometrial cancer. 
WP7 - Involved researchers:
1. Lorenza Driul (DAME)
2. Stefano Restaino (ASUFC-Udine)
3. Anna Biasioli (ASUFC-Udine)
4. Monica della Martina (ASUFC-Udine)
5. Vetrugno (DAME)
6. Monica Anese (DI4A)

According to the reports of the World Health Organization, in 2018, falls represented the second cause of unintentional injury deaths worldwide, only exceeded by road traffic injuries. Consequently, this problem has generated a wide range of studies aimed at developing e
effective ways to detect such accidents.
Computer Vision has recently seen the dawn of new era with the advent of Deep Learning techniques that have significantly improved the performance on many tasks. Recently, Computer Vision techniques based on deep learning managed to obtain great fall classification results, employing Convolutional Neural Networks, Recurrent Neural Networks and many combinations of those.
However, despite the large number of pieces of research published in recent years around the problem of fall detection, there is a poor choice of datasets containing fall videos. Factors such as the accidental nature of a fall event and the privacy of the subject involved led to the creation of datasets which include simulated falls performed by actors in a controlled environment.  Yet, the availability of such datasets is very scarce.
In addition, video data could also be complemented by other types of sensors such as accelerometers that could be combined via Data Fusion techniques to perform real-time detection of fall accidents. The system would therefore be able to trigger an immediate alarm to care-givers.
The objective of this WP is to develop a new dataset of simulated falls for experimenting Deep Learning techniques for automatic fall accident detection.
WP8  Involved researchers:
1. Lauro Snidaro (DMIF)
2. Andrea Apicella (DMIF)
3. Vincenzo Della Mea (DMIF)
4. Alvisa Palese (DAME)
5. Vittorio Bresadola (DAME)