Institute for Cell and Molecular Biosciences

Staff Profile

Emeritus Professor Thomas Kirkwood

Emeritus Professor

Background

Qualifications:                             

BA Mathematics, University of Cambridge, 1972.

MSc Applied Statistics, University of Oxford, 1973.

PhD Biology, University of Cambridge, 1983.


Previous positions:

2011 – 2015  Associate Dean for Ageing, Newcastle University

2004 – 2011  Director, Institute for Ageing and Health, Newcastle University

1999 – 2004  Head, Department of Gerontology, Newcastle University

1999 – 2015  Professor of Medicine, Newcastle University

1993 – 1999  Professor of Biological Gerontology, University of Manchester

1988 – 1993  Head, Laboratory of Mathematical Biology, MRC National Institute for Medical Research, London

1981 – 1988  Staff Scientist, then Senior Staff Scientist (1987), Computing Laboratory, MRC National Institute for Medical Research, London.

1973 – 1981  Scientist, then Staff Scientist (1979), Statistics Section, National Institute for Biological Standards and Control, London.


Honours and distinctions:

Karger Prize 1984 (international science prize for an article on cellular ageing)

Verzar Medal, Vienna 1994

Fellow, Institute for Advanced Study, Budapest 1997

BBC Reith Lecturer ‘The End of Age’ 2001 (www.bbc.co.uk/radio4/reith2001)

Fellow, Academy of Medical Sciences 2001

Honorary Fellow, Faculty of Actuaries 2002

Royal Institution Dale Prize 2002 (featured as an Editorial in Nature DOI: 10.1038/417471a)

Honorary Life Member, Royal Institution 2002

Honorary Doctor of Science, University of Hull 2003

Cohen Medal of the British Society for Research on Ageing 2006

Honorary Life Member, British Society for Research on Ageing 2011

National Institute for Health Research, Senior Investigator 2009

CBE (Commander of the Order of the British Empire) 2009 (from Her Majesty the Queen)

Queen’s Anniversary Prize for Higher Education 2009 (from Her Majesty the Queen; I led the research programme on ageing for which this award was made to Newcastle University)

Excellence with Impact Prize, BBSRC 2011 (awarded to Institute for Ageing and Health)

Ipsen Foundation Longevity Prize 2011

Fellow, Royal College of Physicians of Edinburgh 2013

Nathan Shock Award Lecture, US National Institute on Aging 2016 (chosen by vote of NIA research staff)

Paton Prize Lecture, World Congress of Physiology 2017


Advisory and professional roles:

Member, UCL Commission for Mission-Oriented Innovation and Industrial Strategy (2018-)

Trustee, Age International (2017-)

Trustee, Dunhill Medical Trust (2017-)

International Scientific Advisory Committee, McMaster Institute for Research on Aging (2017-)

Government Office for Science, Expert Group on Ageing (2014-2016)

This relates to a Foresight project providing the UK government with the evidence to develop policies to address the challenges and opportunities of population ageing.

Royal Society, Research Grants Committee (£20k) (2014-)

Chair of the Jury of the Ipsen Foundation Longevity Prize (2014-2018)

International prize for research on the science of longevity.

Trustee Director, BIG Lottery Centre for Ageing Better (2013-2015)

I was a founding trustee director for this centre; I stepped down after the grant of £50M had been secured from BIG Lottery.

AXA Research Fund, President of Scientific Board (2012-)

The AXA Research Fund supports research at the highest standard of excellence in leading academic institutions around the world; the Fund is supported by the AXA insurance group but operates its own selection processes to choose research that is independent from the company’s business; I chair the board and provide strategic leadership.

Trustee, Cumberland Lodge (King George VI and Queen Elizabeth St Catharine’s Foundation) (2007-2016)

Government Office for Science, Foresight Theme Leader “Mental Capital Through Life” (2007-9)

This was a Foresight project on Mental Capital and Wellbeing.

Mechanisms of Ageing and Development, Editor (2000-2012)

PLoS Biology, Editorial Board (2005-)

Science and Industry Council of North England (2007-9)

International Association of Gerontology, European President (Biology) (2003-7)

Trustee, International Longevity Centre – UK (2006-8)

Academy of Medical Sciences, Council Member (2002-5)

House of Lords Science & Technology Select Committee Inquiry into Ageing (2004-6)

My role as Specialist Adviser to the Select Committee was to advise the committee on its agenda, selection of witnesses and questions to be asked, and to draft the report.

Biotechnology and Biological Sciences Research Council, Council Member (2001-2004)

UK Foresight Task Force on Healthcare for Older People, Chair (1999-2001)

British Society for Research on Ageing, Chair (1992-1999)

International Biometric Society (British Region), President (1998-2000)

Research into Ageing, Trustee (1998-2000)

Research into Ageing, Research Advisory Council (1992-2000), Chair (1996-2000)

Wellcome Trust, Basic Sciences Interest Group (1992-7)

This group selects candidates from among the very best scientists in their fields to receive the highly prestigious Wellcome Trust Senior Fellowships

Wellcome Trust, Mathematical Biology Panel (1993-7)

This panel selected projects to help grow the innovative cross-disciplinary field that is now well-established bridging mathematics and biology.

Medical Research Council, Human Genome Mapping Project Committee (1991-3)

This panel selected projects to fund in the earliest stages of the human genome project.

Research

Research Interests

Evolution and genetics of ageing

Starting in 1977, I suggested that a major contribution to understanding ageing can be achieved by linking the evolutionary and physiological approaches in a concept called the disposable soma theory.  This predicts that: (1) ageing is due to evolved limitations in investments in somatic maintenance and repair, due to competing priorities of reproduction; (2) ageing therefore results from the accumulation during life of damage in cells and tissues; (3) multiple mechanisms contribute to ageing (since there are multiple forms of somatic maintenance, all of which are subject to the same optimality process); (4) the principal genes determining longevity and rate of senescence are genes specifying the levels of maintenance functions (e.g. DNA repair genes, antioxidant enzymes, stress proteins); (5) the ageing process is intrinsically stochastic, but that longevity is programmed, on the average, through the settings of genes of the type just considered; (6) maximum life span is not clock-driven but malleable, e.g. through modifying exposure to damage or enhancing somatic maintenance functions.

I have used these ideas to explore life history evolution (eg evolution of menopause) and the optimal allocation of metabolic resources in varying environments (eg life extension through rodent calorie-restriction).  Such models are important for understanding the genetic architecture of the life history and have major relevance for genome research on longevity.  With Rudi Westendorp (University of Leiden), we reported in Nature the first evidence for a trade-off between human longevity and fertility.

In genome studies on human ageing, I pioneered novel approaches to the analysis of gene polymorphisms affecting human longevity in collaboration with Francois Schachter and Daniel Cohen (Centre d’Etude du Polymorphisme Humain), and subsequently developed models of genetic and non-genetic factors affecting human longevity.  Emerging from the disposable soma theory, there is a growing recognition that the development of the senescent phenotype is strongly affected by intrinsic stochastic factors (chance), as well as by genes and environment.  A major synthesis of this new perspective was published in collaboration with Caleb Finch (University of Southern California).

Mechanisms of cellular ageing

A central problem in experimental gerontology is to understand how cells accumulate damage during ageing and how age changes at the cell level produce age-related dysfunction and disease within tissues and organs.  In collaboration with Chris Potten (Paterson Institute for Cancer Research), I obtained some of the first direct evidence of age changes occurring within tissue stem cells in the intestinal epithelium.  These changes involve increased susceptibility to genotoxic agents (low-dose irradiation) and impaired regenerative capacity.  In a different context, I showed that primary skin fibroblasts from long-lived mammalian species have greater intrinsic capacity to withstand a variety of stresses in vitro than cells from short-lived species.  This confirmed a key prediction of the disposable soma theory and points to the central role of cell maintenance and stress response systems in ageing and longevity.

Another key prediction of the disposable soma theory is that there is no single mechanism of cell ageing, but rather that multiple mechanisms operate together.  I have developed this concept of a network theory of cellular ageing in a series of theoretical models that examined the major candidate mechanisms of cell ageing in an integrated way (collaboration with Axel Kowald, Humboldt University).  This work led the way in establishing the importance of systems-biology approaches to addressing the inherent complexity of the ageing process. Within the Centre for Integrated Systems Biology of Ageing and Nutrition, established with BBSRC funding in 2005, major programmes have examined the complex pathways responsible for phenomena such as replicative senescence, using a combination of computational and experimental approaches.

Most recently, in collaboration with the Center for Healthy Aging at the University of Copenhagen, where I have been a part-time professorship since 2016 (now affiliate professor), I am a co-investigator in a Challenge Programme funded by the Novo-Nordisk Foundation to make use of big data to examine trajectories of ageing. This involves working to connect research on systems biology of molecular mechanisms with large volumes of pathophysiological samples as well as with data collected by national bodies such as Statistics Denmark.

Ageing in human populations

In recognition of the fact that there was then limited information about the spectrum of health in the general population at advanced age, I led the establishment of the Newcastle 85 Study which since 2006 has been examined in great detail the many factors that influence trajectories of health beyond age 85. Following a two year pilot study, during which the procedures were rigorously tested and refined, the main study sought to recruit as many as possible of the population of Newcastle upon Tyne and North Tyneside who had been born in 1921. The study has included a wide range of domains of assessment (e.g. health, via nurse assessment and GP record review; cognitive and physical function; sleep; sensory function; psychology; socioeconomics; biological markers; genetics).


Publications