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Overview

Theo Murphy international scientific meeting organised by Dr Helen Weavers and Professor Anna Jazwinska.

Most animal and plant tissues have an intrinsic ability to withstand day-to-day stress, but many also exhibit extraordinary adaptive responses to stress that drive increased ‘resilience’ against further insult. This inter-disciplinary meeting will showcase cutting-edge research from basic scientists and clinicians exploring the mechanistic basis and translational potential of these remarkable phenomena, including the role of diet, ageing and biomechanics.

More information about the schedule of talks and speaker biographies will be available soon. Meeting papers will be available in a future issue of Philosophical Transactions of the Royal Society B

Poster session

There will be a poster session on Wednesday 26 April. If you would like to apply to present a poster please submit your proposed title, abstract (not more than 200 words), author list, name of proposed presenter and institution to the Scientific Programmes team no later than Friday 31 March 2023. Please include the text 'Poster abstract submission - Tissue resilience' in the email subject line. Please note that posters are selected at the scientific organisers' discretion. 

Attending this event

This meeting is intended for researchers in relevant fields. This will be a residential meeting held at INNSiDE Manchester, 1 First Street, Manchester, M15 4RP. 

  • Free to attend
  • Limited places, advance registration essential
  • This is an in-person meeting only
  • Meals during the meeting can be paid for through Eventbrite (lunches on both days of the meeting and dinner on the first night)
  • Participants will need to book their own accommodation with INNSiDE Manchester. 

Enquiries: contact the Scientific Programmes team.

Wound inflammatory response (Helen Weavers)

Image: Wound inflammatory response (Helen Weavers)

Zebrafish heart (Anna Jazwinska Lab)

Image: Zebrafish heart (Anna Jazwinska Lab)

Organisers

Schedule


Chair

09:00-09:05
Welcome by the lead organiser
09:05-09:30
Synaptic and metabolic targets for ischemic neuroprotection by preconditioning paradigms

Abstract

Abstract of the talk will be available soon. 

Speakers

09:30-09:45
Discussion
09:45-10:15
Tissue conditioning 2

Abstract

Abstract of the talk will be available soon.

10:15-10:30
Discussion
10:30-11:00
Break
11:00-11:30
Tissue conditioning 2

Abstract

Abstract of the talk will be available soon.

11:30-11:45
Discussion
11:45-12:15
Intrinsic stress resilience 1

Abstract

 

12:15-12:30
Discussion

Chair

13:30-14:00
Intrinsic stress resilience 2

Abstract

 

14:00-14:15
Discussion
14:15-14:45
Intrinsic stress resilience 3

Abstract

 

14:45-15:00
Discussion
15:00-15:30
Break
15:30-16:00
Biomechanics of resilience 1

Abstract

 

16:00-16:15
Discussion
16:15-16:45
Biomechanics of resilience 2
16:45-17:00
Discussion
17:00-18:00
Poster session
09:00-09:30
Remote conditioning 1

Abstract

Abstract of the talk will be available soon.

Speakers

09:30-09:45
Discussion
09:45-10:15
Cardio-resilience due to chronic or brief stresses: pathology vs. conditioning

Abstract

The response of the adult human myocardium to a relatively long sustained injurious insult (e.g., during cardiac surgery) can be altered by pathology. The progression of different cardiac diseases triggers different remodelling (metabolic, molecular, structural etc) that determine how the heart responds to the insult and the extent of injury. Additionally, brief non-injurious stresses applied directly to the heart (conditioning) are known to protect the myocardium against a long sustained injurious insult. The conditioning can also be a remote one (Remote Ischaemic Preconditioning, RIPC) where a brief stress applied to a distant organ is cardioprotective. RIPC has advantages but its clinical translation in disease setting has been controversial. Understanding of disease-induced cardiac remodelling and mechanisms underlying conditioning is important for mobilising cardiac intrinsic protective pathways.

Speakers

10:15-10:30
Discussion
10:30-11:00
Break
11:00-11:30
Cardioprotection by remote ischemic conditioning (RIC) and its translation

Abstract

There is still a medical need for cardioprotection beyond that by rapid coronary reperfusion, since mortality and morbidity, notably from heart failure, in patients with acute myocardial infarction remain high. Brief cycles of ischemia/reperfusion in a tissue or organ remote from the heart (RIC) reduce infarct size from sustained myocardial ischemia/reperfusion in all species tested so far, including humans. In the researchers' pig model of reperfused acute myocardial infarction, RIC before (preconditioning) or during (perconditioning) coronary occlusion reduces infarct size. The signal transfer of RIC from the periphery to the heart involves humoral and neuronal factors. Humoral factors of RIC can be transferred with plasma preparations from one individual to another, even across species. The neuronal signal transfer involves peripheral sensory afferents, the central nervous system and vagal efferents. The spleen serves as a decisive relay organ of RIC and releases humoral cardioprotective factors upon vagal activation. The protective signal transduction in the myocardium involves STAT3 activation and improved mitochondrial function. Repeated blood pressure cuff inflation/deflation on the arm or leg has been demonstrated to reduced infarct size and improve clinical outcome in patients undergoing coronary bypass surgery when this RIC was used in a preconditioning mode and in patients with reperfused acute myocardial infarction when RIC was used in a perconditioning mode. However, larger clinical trials with neutral results on RIC also exist and have raised disappointment on its translation. Co-morbidities, co-medications but also a primordial myocardial non-responsiveness may interfere with cardioprotection by RIC. It appears important to focus on RIC in patients who really need adjunct cardioprotection because they are at high risk and/or have suboptimal therapeutic reperfusion, and respective trials are underway. Humoral factors of RIC in humans can also be transferred to bioassay recipient hearts. In cardiosurgical patients, the myocardial signal tranduction of RIC also involves STAT activation and improved mitochondrial function. 

Nat Rev Cardiol 12,2020,773-89; Basic Res Cardiol 117,2022,39 and 58; AJP 323,2022,H 1365-75

Speakers

11:30-11:45
Discussion
11:45-12:15
Remote conditioning 4

Abstract

 

12:15-12:30
Discussion
13:30-14:00
Resilience, diet and ageing 1

Abstract

 

14:00-14:15
Discussion
14:15-14:45
Resilience, healthy ageing and longevity: a biological perspective

Abstract

More than 60 years of biogerontological research has led to the understanding that ageing is not a disease, and there are no ageing-causing gerontogenes. Genes determine our ability to survive and maintain health for a limited period, known as the essential lifespan of the species. These longevity-assurance genes or vitagenes create a homeodynamic space, characterised by stress response, damage control and constant remodelling. Resilience, robustness and longevity of an organism are the primary expressions of the homeodynamic space. We are, of course, able to live much longer than our species’ essential lifespan, but our imperfect homeodynamic space progressive shrinks due to the accumulation of molecular damage, and makes us less robust, less resilient and more prone to physical impairment and consequent diseases. Among various interventional approaches being tested and developed, an evidence-based holistic scientific strategy towards healthy ageing is that of mild stress-induced hormesis. Physical, nutritional and mental stress-inducing hormetins lead to the strengthening of the homeodynamics of maintenance and repair systems. Exercise, heat and irradiation are examples of physical hormetins, which activate various stress responses. Several non-nutritional chemical components in the food, such as flavonoids and polyphenols present in spices, herbs and other sources, are examples of nutritional hormetins. Calorie restriction and intermittent fasting are hormetins, which activate the autophagic and sirtuin-mediated stress responses. Intense brain activity and focussed attention comprise mental hormetins. A combination of different hormetins offers the possibility of recovering and enhancing body’s resilience and robustness, and help achieving healthy ageing and longer lifespans. 

Speakers

14:45-15:00
Discussion
15:00-15:30
Break
15:30-16:00
The role of metabolic resilience in healthy aging

Abstract

Energy metabolism provides fuel for basic and adaptive activities of the cell including quality control and repair processes. Moreover, metabolic plasticity is directly required for the successful adaptation of the cells to extrinsic and intrinsic stressors, and it supports the healthy longevity at the organismal level. In previous work, the authors of this study found that the adaptive capacities of mitochondria, lipid metabolism and glycolysis fail with age in an interconnected fashion. This failure has an impact not only on the general well-being of the organism but also on the positive effects of the resilience-promoting treatments such as dietary restriction (DR) and DR-mimetic compounds like metformin. Particularly, the scientists found that resilience benefits of metformin in non-diabetic C. elegans are abrogated and even reversed following late-life onset intervention, with life extension of metformin-exposed young nematodes mirrored by toxicity of this drug in old animals and cells. In this talk Dr Maria Ermolaeva will discuss molecular mechanisms that underlay late life failures of the conventional metabolic resilience treatments, and will speak about new intervention paradigms discovered by her group, which facilitate metabolic plasticity independently of age.  

Speakers

16:00-16:15
Discussion
16:15-17:00
Panel discussion/overview