MIRAI 2.0 R&I Week 2021

Ageing

Tentative program

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Moderators:
Anna Sandgren, Linnaeus University
Nobuhiro Takahashi, Tohoku University
Yoshihisa Hirakawa, Nagoya University

Moderators:
Elenor Kristoffersson, Örebro university
Sofi Fristedt, Jönköping University
Yuto Kitamura, University of Tokyo
Kazuhiro Tsuga, Hiroshima University

Moderators:
Carl-Johan Boraxbekk, Umeå University
Takayuki Akimoto, Waseda University

SPEAKERS

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Boo Johansson is a senior professor at the Department of Psychology at the University of Gothenburg. He specializes in geropsychology. Prof Johansson’s research interests include cognition, cognitive and mental health in late adulthood and aging. Normal aging, compromised cognition, and dementia. Clinical, twin, and longitudinal population-based aging studies. He is a steering committee member of AgeCap Centre for Ageing and Health, a multidisciplinary research centre hosting more than 160 researchers from 25 disciplines working interdisciplinary to increase the quality of life and societal participation of older persons.

The pandemic demonstrates the need for a multidisciplinary perspective of ageing
Research on ageing requires broad multidisciplinary perspectives. At the fundamental level, the focus is on age-related underlying biological changes in cells, tissues and organ systems which affects functioning and ultimately survival. At focus at the psychological level are mental and neural processes involved in cognition, experiences of wellbeing and how this is reflected in individuals coping behavior with internal and external environmental demands. Social ageing refers to how individuals are viewed and treated depending on their age and how this affects older adults’ integration and participation in the societal life. The current Covid-19 pandemic clearly illustrates the need to take all the above perspectives into account for determination of age-related risks from a biological, psychological, and social perspective, and how this knowledge can inform societal policies, preventative, and treatment interventions.        

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Ingmar Skoog is the Director of the Centre for Ageing and Health AGECAP, including 130 researchers from 16 institutions and 6 faculties at the University of Gothenburg, Sweden, and is leading the Neuropsychiatric Epidemiology Unit (Epinep) at the Sahlgrenska Academy. He has been involved in epidemiological research since 1983, and is PI of the Gothenburg H70 Birth Cohort Studies, including the 95+ study. He has published more than 400 scientific papers, and been invited speaker to more than 300 international meetings. His main research interest is the epidemiology of ageing, including time-trends, and dementia, and mental disorders in old age. (M.D. in 1985, Ph.D. in 1993, specialist in psychiatry 1993, and professor in Psychiatry in 2001)

The societal response to Covid-19 and its effect on older adults wellbeing and everyday life
In Sweden, it soon became clear that authorities and experts in virology lacked knowledge about aging. Much emphasize during the first wave of the pandemic was put on protecting and isolating people above age 70 years, who were all regarded to be frail and helpless. This led to a lot of ageism and prejudice about older people in a country where the view of older people was already negative. However, it soon became clear that 75% of all deaths in covid 19 occurred among the 3% of the population who had old age care. This took authorities by some surprise. Reasons included that people in old age care are frail, but also that they meet more younger people at a very close distance than any other group in society. This led to a lot of discussion in Sweden about different aspects of old age care, and the quality of the care.

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Effectiveness of 222-nm ultraviolet light on disinfecting microorganisms
Approximately half of the surfaces present in hospital premises are insufficiently cleaned during the manual cleaning. Recently, non-touch disinfection technologies using ultraviolet (UV) light have been increasingly used in health care settings in an attempt to decrease the transmission of nosocomial pathogens and prevent health care-associated infections.Most UV disinfection systems use germicidal lamps emitting UV radiation C (UVC) around 254 nm. However, it is well known that 254-nm UVC is harmful to the skin and eyes. Previous reports demonstrated that 222-nm UVC light, belonging to far-UVC (207-222 nm), has the same highly effective germicidal proper-ties as 254-nm UVC; however, it is less harmful to the skin and eyes than 254-nm UVC because far-UVC light has a very limited penetration depth in the skin or eye. Our group demonstrated the efficacy of 222-nm UVC irradiation against SARS-CoV-2 or multidrug-resistant bacterial contamination in in vitro experiment. Further evaluations of the safety of 222-nm UVC light to the skin and eyes are required to establish an effective strategy for UV disinfection of hospital or public space.

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Cytoprotective and Anti-Aging Function of NRF2 and its Role in Sulfur Metabolism
Keap1-NRF2 system is a sulfur-based cytoprotection mechanism and makes critical contributions to prevention and alleviation of various diseases relating to oxidative stress.  Recent studies of ours and others also clarified that appropriate activation of NRF2 has anti-aging effects by limiting accumulation of oxidative damages of tissues. 
KEAP1 utilizes multiple cysteine residues for sensing electrophiles, whereas NRF2 activates various genes regulating sulfur-involving reactions.  Although NRF2 enhances mitochondrial activity, a precise mechanism has not been fully understood.  Based on our recent finding that mitochondrial sulfur metabolism makes a substantial contribution to mitochondrial energy metabolism, we hypothesized that NRF2 promotes the mitochondrial activity through promoting the sulfur metabolism.  Since SLC7A11 encoding a cystine transporter, xCT, is a well-known NRF2 target gene, NRF2 was likely to enhance the mitochondrial sulfur metabolism by increasing the supply of their substrate, cysteine. 
Indeed, cystine restriction in the culture medium and xCT inhibition by sulfasalazine both decreased the mitochondrial membrane potential (MMP), suggesting that sufficient cysteine availability is required for the maintenance of MMP. 
To examine contributions of the mitochondrial sulfur oxidation pathway mediated by SQOR, ETHE1 and SUOX and the mitochondrial persulfide production catalyzed by CARS2 to the MMP maintenance, we knocked down each enzyme gene and examined its impact on the MMP.  The MMP was significantly decreased by knockdown of these enzymes except for SUOX.  Among them, we found that SQOR, encoding sulfide-quinone oxidoreductase (SQOR), is directly activated by NRF2.  Increased mitochondrial membrane potential by NRF2 activation was canceled by simultaneous suppression of SQOR.  These results suggest that one of the mechanisms for NRF2-dependent mitochondrial activation is the facilitation of sulfur metabolism in mitochondria following the increased cystine uptake.

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