Ageing and Frailty

Young female face on the left merging with old female face on the right.

We research inflammatory processes that drive human ageing and translate this to interventions to prevent age-related disease and frailty and improve outcomes after trauma. Our discovery science is multidisciplinary including epigenetics, immunometabolism, microbiome, immunothrombosis and immunosenescence.  We lead two national centres of excellence: MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research and the Scar Free Foundation Centre for Conflict Wound Research.

DSC_0933-4 - simon jonesTheme Lead (Interim)

Professor Simon Jones

Professor in Musculoskeletal Ageing

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Research sub-themes

Ageing and Multimorbidity

Ageing and Multimorbidity

Co-leads: Dr Thomas Jackson and Professor Joao Pedro de Magalhaes

Multimorbidity is defined as the co-occurrence of 2 or more long-term conditions and advancing age is the biggest risk factor for developing multimorbidity. With changing demographics and an ageing population, the prevalence of multimorbidity is increasing with significant consequences for health and social care costs. Although age is the major risk factor for multimorbidity, the role of biological ageing mechanisms is currently unknown. This limits our ability to tackle the primary drivers of multimorbidity and maintains the status quo of treating component diseases individually, resulting in polypharmacy.

The diseases that older adults acquire are not random and distinct clustering of diseases is seen, such as clusters of musculoskeletal or cardiovascular conditions. This suggests that there are common mechanisms driving these associations. Our overall aim is to identify modifiable underlying ageing mechanisms associated with clusters of multimorbidity, test interventions (drugs or lifestyle) to inhibit these mechanisms and use novel clinical trial designs to carry out clinical trials in multimorbid patients. 

 

Animated image of an elderly couple holding a protection shield and heart

 

Artificial Intelligence (AI) and Multimorbidity

We use data from primary care (GP) and hospital records to define multimorbidity clusters and also the way these clusters develop over time. This will help us to identify those adults at risk of progressing to multimorbidity and allow us to recruit these adults to intervention studies.

Key datasets include electronic health records at the Queen Elizabeth hospital Birmingham, where our department is located. These data allow also us to track which medicines patients are given and how this influences their future health.

Meet the team:

 

Animated image of doctors interacting with digital interfaces and checking health data

Biological Mechanisms of Multimorbidity

Recent advances in ageing research have led researchers to propose that 12 processes drive the ageing phenotype, termed the Hallmarks of Ageing. Four modifiable hallmarks, which already have therapeutic agents available, were identified as linked to multimorbidity namely:

1) Deregulated nutrient sensing;
2) Mitochondrial dysfunction,
3) Cell senescence;
4) Altered intercellular communication (inflammation).

Additionally, it has now become clear that the gut microbiome changes with age and has a major influence on how well we age, notably affecting increased inflammation with age. This hallmark is readily modifiable by diet and probiotic supplementation.

We are determining the presence of these hallmarks in patients in the different multimorbidity clusters to determine their possible role in multimorbidity development. We are also using animal models to test the impact of repurposed drugs that inhibit the hallmarks to determine the impact on multimorbidity.

Meet the team:

 

Animated image of an elderly man sitting in a medical office at a table opposite a doctor having a consultation

Frailty Mechanisms

Frailty Mechanisms

Co-leads: Professor Janet Lord and Dr Niharika Duggal

Frailty is a state of increased vulnerability to, and impaired recovery from, stresses such as infections and falls. It involves compromise to the functioning of multiple body systems which results in a loss of resilience.

Advancing age is the major risk factor for frailty and with increasing life expectancy and the ensuing heightened prevalence of frailty, there is a need to understand the underlying factors driving this syndrome.

We are using cohorts of non-frail, pre-frail and frail older adults to understand the heterogeneity in those presenting with frailty. In so doing we aim to improve the stratification of frail adults, identify processes driving the development of frailty and intervene to prevent or reverse its progression.

Our MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research is a major vehicle for this research. 

In addition, we also consider the impact of a major trauma on ageing trajectories, working with both civilian and military trauma victims. 

 

Animated image of male individual pushing an elderly woman in a wheelchair to a doctor's appointment

Trauma and Frailty

Trauma is the main cause of death in young adults but with improvements in experimental medicine, more victims now survive. However, these survivors have shortened lifespans and develop many age-related diseases earlier than their uninjured counterparts.

In addition, common injuries in older adults, such as hip fractures, have poor outcomes with many patients progressing rapidly to frailty. These data suggest that injuries accelerate the ageing process, shortening lifespan and healthspan.

This theme investigates the impact of trauma in young and old adults on ageing processes and the mechanism involved.

Meet the team:

 

Animated image of an elderly man using a walker and standing in a doctor's office talking to a doctor. The elderly man is being assisted and supported from the back by another man.

Lifestyle and Ageing Trajectories

It has been long established that physical activity and diet are major influences on how well we age. Understanding exactly which aspects of ageing can be prevented by maintained levels of physical activity and which are intrinsic ageing processes is poorly understood.

This theme works with a cohort of lifelong exercisers to address this question. It has also become clear that the microbiome is a major influence on ageing trajectories and microbial dysbiosis is now included as one of the hallmarks of ageing.

Meet the team:

 

Animated image of two elderly men standing side by side. Elderly man on the right looks exhausted and holding his lower back in pain and is using a walking stick. Elderly man on the left is standing upright and lifting dumbbells above his head.

Immunometabolism and chronic inflammatory disease

Immunometabolism and chronic inflammatory disease

Lead: Professor Claudio Mauro

This theme investigates the interconnections between metabolic and inflammatory pathways and how systemic and local metabolic alterations in diseases with an inflammatory component lead to aberrant immune cell responses, which favour both the establishment and the propagation of inflammation.

In particular, it focuses on unveiling how specific metabolites, including lactate and fatty acids, act as signalling molecules modulating many aspects of the immune-inflammatory response in health and disease.

Diseases studied include Rheumatoid arthritis, Sjögren’s disease, Cardiovascular (Atherosclerosis), Osteoarthritis and Tuberculosis (TB).

Meet the team:

 

Animated image of female doctor injecting vaccine syringe in an older man's arm

Immune-metabolic host responses in tuberculosis disease

Tuberculosis is a major public health problem and new treatments are urgently needed. New drug-discovery approaches focus on changing the way our immune system reacts to infection, helping it to fight back.

During an infection, our immune cells engage on glycolysis to rapidly produce energy to mount an efficient response. This results in lactate formation, first considered a waste product, now recognised as a modulator of immune responses, a concept we seeded in the research community. The way in which lactate exerts this effect is not known. 

Our immune-metabolic research investigates the mechanisms behind lactate-mediated driven immune functions, trying to understand exactly how lactate impacts immune function and infection outcome.

We use state-of-the-art techniques, including high resolution microscopy at the single cell level, and immune cells from human lung, a rare and precious resource.

We work on assessing the therapeutic potential of targeting lactate to treat tuberculosis using a variety of human and murine models. Our research represents a unique opportunity to ease the pathway towards novel treatments for an ancient disease.

Meet the team:

 

Animated image of doctors interacting with a digital interface displaying a human lung and diagnosing lung conditions. One doctor is touching an iPad and one doctor is holding a magnifying glass whilst another doctor is looking at the interface.

Inflammatory mechanisms that drive degenerative joint pathology in osteoarthritis

Inflammatory mechanisms that drive degenerative joint pathology in osteoarthritis

Lead: Professor Simon Jones

It is now recognised that osteoarthritis (OA) is a disease of the whole joint, including not just the articular cartilage but also the subchondral bone, the synovium and the skeletal muscle tissue. It has also become clear that joint inflammation is a central hallmark of OA throughout the disease course, exacerbating joint damage and causing joint pain.

Combining clinical studies with in vitro and ex vivo human tissue models, this team is focused on understanding the inflammatory and age-related mechanisms that mediate the pathological changes in these joint tissues – including the degradation of articular cartilage, changes in the functional role of osteoblasts and osteocytes in abnormal bone remodelling, skeletal muscle atrophy and synovial inflammation (synovitis).

Particular areas of interest are understanding the effect of obesity on OA joint pathology, and in determining the role of non-coding RNAs (microRNAs and long non-coding RNAs) in mediating inflammatory responses within the joint.

Meet the team:

 

Animated image of doctors examining human foot joints

Ageing mechanisms and delirium

Ageing mechanisms and delirium

Lead: Dr Thomas Jackson

Delirium is a sudden loss of brain function, secondary to infection, surgery, and other inflammatory insults. 

Delirium affects 1 in 5 people in hospitals, from children to the very old.  It is more common in Intensive care settings, and among older people with cognitive impairment. 

People who develop delirium are more likely to die in hospital, and have an increased risk of developing dementia. 

Despite this importance, we know little about what causes delirium to occur and how it causes these long-term effects. There are currently no treatments to improve delirium once it has started.

This theme investigates if changes to the immune system that occur with age lead to an altered immune response that causes delirium. 

In particular, we are investigating how these changes increase the transfer of inflammatory signals outside the brain, to inside the brain. We also partner with colleagues in Oxford and Nottingham to deliver clinical trials of immune modulating drugs in people having hip fracture surgery.

Find out further information about the WHITE LIT trial which seeks to investigate the best treatments to prevent and treat confusion and delirium after surgery in adults with a broken bone in the leg.

WHITE LIT Trial

Meet the team:

 

Animated image of a doctor and elderly patient using a walker with a large human brain in the background, displaying the concept of brain inflammation.

Mitochondrial ageing and diabetes

Mitochondrial ageing and diabetes

Lead: Dr Jose Hombrebueno

Mitochondria are essential for tissue homeostasis, by regulating central processes involved in metabolism, inflammation, and cellular aging. Given their pivotal role, mitochondrial dysfunction has emerged as a key pathogenic factor for the multiple conditions of diabetes.

Our theme focuses on understanding how old, damaged mitochondria can be rejuvenated pharmacologically. We are particularly interested in targeting the processes that control mitochondrial turnover, so that old mitochondria can be efficiently replaced by new functional units (i.e., like replacing a battery).

Using state-of-the-art (drug) screening platforms, along with disease models and clinical technology to assess mitochondrial health, our team is developing new molecules with bioactivity to rejuvenate mitochondria at the multisystem level, with potential to:

  1. Tune-up immunity;
  2. Alleviate cellular ageing;
  3. Rescue stem-cell exhaustion

Our ultimate goal is to translate these therapies to alleviate chronic disease in diabetes.

Meet the team:

 

Animated image of hands holding a glucose meter measuring their blood sugar levels using the finger stick.

Publications, Grants and Patient Partnerships

Publications

Ageing and Multimorbidity

  • Sharma-Oates, A, Zemedikun, D.T., Kumar, K, Reynolds, J.A., Jain, A, Raza, K, Williams, J.A., Bravo, L, Cardoso, V.R., Gkoutos, G, Nirantharakumar, K, and Lord, J.M. (2022) 'Early onset of immune mediated diseases in minority ethnic groups in the UK'. BMC Med, 20:346.
  • Zemedikun, D.T., Lee, H, Nirantharakumar, K, Raza, K, Chandan, J.S., Lord, J.M. and Jackson, T.A. (2022) 'Comorbidity phenotypes and risk of mortality in patients with osteoarthritis in the UK: A latent class analysis'. Arthr Res Ther., 24(1):231.
  • Subramanian, A, Nirantharakumar, K, Hughes, S, Myles, P, Williams, T,  Gokhale, K, Taverner, T, Chandan, J.S., Brown, K, Simms-Williams, N, Shah, A.D., Singh, M, Kidy, F, Okoth, K, Hotham, R, Bashir, N, Cockburn, N, Lee, S.I., Turner, G.M., Gkoutos, G.V., Aiyegbusi, O.L., McMullan, C, Denniston, A.K., Sapey, E, Lord, J.M., Wraith, D.C., Leggett, E, Iles, C , Marshall, T, Price, M, Marwaha, S, Davies, E.H., Jackson, L, Matthews, K.L., Camaradou, J, Calvert, M, and Haroon, S. (2022) 'Symptoms and risk factors for long COVID in non-hospitalised adults'. Nature Med, 28, 1706–1714.
  • Cox, L.S. and Lord J.M. (2021) 'Perspective: Targeting ageing cells improves survival', Science, 373:281-282.
  • Alsaleh, G, Panse, I, Swadling, L, Zhang, H, Meyer, A, Lord, J.M., Barnes, E, Klenerman, P, Green, C, and Simon, A.K. (2020) 'Autophagy in T cells from aged donors is maintained by spermidine, and correlates with function and vaccine responses', eLIFE, 9: article 57950.
  • Ford, G.A., Lord, J.M., Ferguson, M.A.J., Bountra, C, and Le Couteur, D. (2020) 'Organizational innovation for developing new medicines that target aging and age-related conditions', J Gerontol. Series A:Biol Sci Med Sci., 75(1):87-88.
  • Ermogenous, C, Green, C, Jackson, T.A., Ferguson, M, and Lord, J.M. (2020) 'Treating age-related multi-morbidity: The drug discovery challenge', Drug Discovery Today, 25:1403-1415.
  • Duggal, N.A., Niemiro, G, Simpson, R.J., Harridge, S.D.R. and Lord, J.M. (2019) 'Can physical activity ameliorate immunesenescence and thereby reduce age-related multi-morbidity?', Nature Rev Immunol., 19:563-572.
  • Sullivan, J, Mirbahai, L, and Lord, J.M. (2018) 'Major trauma and acceleration of the ageing process', Ageing Res Rev., 48:32-39.

Frailty Mechanisms

  • McAuley, H.J.C., Evans, R.A., Bolton, C.E., Brightling, C.E., Chalmers, J.D., Docherty, A.B., Elneima, O, Greenhaff, P.L., Gupta, A, Harris, V.C., Harrison, E.M., Ho, L-P, Horsley, A, Houchen-Wolloff, L, Jolley, C.J., Leavy, O.C., Lone, N.I., Man, W D-C, Marks, M, Parekh, D, Poinasamy, K, Quint, J.K., Raman, B, Richardson, M, Saunders, R.M., Sereno, M, Shikotra, A, Singapuri, A, Singh, S.J., Steiner, M, Tan, A.L., Wain, L.V., Welch, C, Whitney, J, Witham, M.D., Lord, J, Greening, N.J., and PHOSP collaborative (2023) 'Prevalence of physical frailty including risk factors up to one year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study', eClinMed, 57:101896.
  • Taylor, J, Greenhaff, P, Bartlett, D.B., Jackson, T, Duggal, N, and Lord, J.M. (2022) 'A Multisystem Physiological Perspective of Human Frailty and its modulation by Physical Activity', Physiol Rev., 103:1137-1191.
  • Doody, P, Asamane, E.A., Aunger, J.A., Swales, B, Lord, J.M., Greig, C.A., and Whittaker, A.C. (2022) 'The prevalence of frailty, and pre-frailty among geriatric hospital inpatients and its association with economic prosperity and healthcare expenditure: A systematic review and meta-analysis of 467,779 geriatric hospital inpatients', Ageing Res Rev., 80:101666.
  • Evans, R.A. et al; PHOSP-COVID collaborative group. (2022) 'Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study', Lancet Resp Med., 10:761-775.
  • Allen, S.L., Seabright, A.P., Quinlan, J.I., Dhaliwal, A, Williams, F.R., Fine, N.H.F., Hodson, D.J., Armstrong, M.J., El Sharkawy, A.M., Greig, C.A., Lai, Y-C, Lord, J.M., Lavery, G.G., and Breen, L. (2022) 'The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth', Cells, 11:1098.
  • Evans, R.A. et al; PHOSP-COVID collaborative group. (2021) 'Physical, cognitive and mental health impacts of COVID-19 following hospitalisation – a multi-centre prospective cohort study', Lancet Resp Med., 9:1275-1287.
  • Dhaliwal, A, Quinlan, J.I., Overthrow, K, Greig, C, Lord, J.M., Armstrong, M.J., and Cooper, S.C. (2021) 'Sarcopenia in inflammatory bowel disease: A narrative overview', Nutrients, 13(2):656.
  • Allen, S, Quinlan, J, Dhaliwal, A, Armstrong, M, Elsharkawy, A, Greig, C, Lord, J, Lavery, G, and Breen L. (2020) 'Sarcopenia in Chronic Liver Disease: Mechanisms and Countermeasures', Am J Physiol: Gastrointestinal Liver Phys, 320(3), G241–G257. 
  • Wilson, D, Drew, W, Jasper, A, Crisford, H, Nightingale, P, Newby, P, Jackson, T, Lord, J.M., and Sapey, E. (2020) 'Frailty is associated with neutrophil dysfunction which is correctable with phosphoinositol-3-kinase inhibitors', J Gerontol Series A: Biol Sci Med Sci., 75:2320-2325.
  • Wilson, D.V., Moorey, H, Stringer, H, Sahbudin, I, Filer, A, Lord, J.M., and Sapey, E. (2019) 'Bilateral anterior thigh thickness: a new diagnostic tool for the identification of low muscle mass?', JAMDA, 20:1247+.
  • Williams, F.R., Lord, J.M., and Armstrong, M.J. (2019) 'Impact of Exercise on Physical Frailty in patients with Chronic Liver Disease', Alimentary Pharmacol Therapeutics, 50:988-1000.
  • Lazarus, N, Lord, J.M., and Harridge, S. (2019) 'The relationships and interactions between age, exercise and physiological function', J Physiol., 597.5: 1299-1309.
  • Fuggle, N.R., Westbury, L.D., Syddall, H.E., Duggal, N.A., Shaw, S.C., Maslin, K, Dennison, E.M., Lord, J, and Cooper, C. (2018) 'Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study', Osteoporosis Int., 29:1581-1589.
  • Duggal, N.A., Pollock, R.D., Lazarus, N.R., Harridge, S, and Lord, J.M. (2018) 'Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood', Aging Cell, 17:e12750.
  • Pollock, R.D., O’Brien, K, Daniels, L.J., Nielsen, K.B., Rowlerson, A, Duggal, N.A., Lazarus, N.R., Lord, J.M., Philp, A, and Harridge, S.D.R. (2018) 'Properties of the vastus lateralis muscle in relation to age and physiological function in master cyclists aged 55-79 years', Aging Cell, 17: article UNSP e12735.

Immunometabolism and chronic inflammatory diseases

  • Wijesinghe, S, Badoume, A, Nanus, D, Sharma-Oates, A, Farah, H, Certo, M, Alnajjar, F.A.Q., Davis, E, Mauro, C, Lindsay, M.A., and Jones, S. (2023), 'Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets', Clinical and Translational Medicine, vol. 13, no. 4, e1232. https://doi.org/10.1002/ctm2.1232.
  • Grudzinska, F, Jasper, A, Sapey, E, Thickett, D, Mauro, C, Scott, A and Barlow, J. (2023) 'Real-time assessment of neutrophil metabolism and oxidative burst using extracellular flux analysis', Frontiers in immunology, vol. 14, 1083072. https://doi.org/10.3389/fimmu.2023.1083072.
  • Farah, H, Wijesinghe, S, Nicholson, T, Alnajjar, F. A. Q., Certo, M, Alghamdi, A. M. A., Davis, E, Young, S, Mauro, C and Jones, S. (2022) 'Differential metabotypes in synovial fibroblasts and synovial fluid in hip osteoarthritis patients support inflammatory responses', International Journal of Molecular Sciences, 23(6), 3266.
  • Macchi, C, Moregola, A, Greco, M. F., Svecla, M, Bonacina, F, Dhup, S, Dadhich, R. K., Audano, M, Sonveaux, P, Mauro, C, Mitro, N, Ruscica, M, and Norata, G. D. (2022) 'Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity', iScience, 25(6,) 104435.
  • Camacho-Muñoz, D, Niven, J, Kucuk, S, Cucchi, D, Certo, M, Jones, S. W., Fischer, D. P., Mauro, C. and Nicolaou, A. (2022) 'Omega-3 polyunsaturated fatty acids reverse the impact of western diets on regulatory T cell responses through averting ceramide-mediated pathways', Biochemical Pharmacology, 204, 115211.
  • Certo, M, Llibre, A, Lee, W. and Mauro, C. (2022) 'Understanding lactate sensing and signalling', Trends in Endocrinology & Metabolism, 33(10), pp.722-735. 
  • Conway, J, Certo, M, Lord, J. M., Mauro, C. and Duggal, N. A. (2022) 'Understanding the role of host metabolites in the induction of immunesenescence: future strategies for keeping the ageing population healthy', British Journal of Pharmacology, 179(9), pp. 1808-1824. 
  • Llibre, A, Dedicoat, M, Burel, J. G., Demangel, C, O'Shea, M. K. and Mauro, C. (2021) 'Host immune-metabolic adaptations upon mycobacterial infections and associated co-morbidities', Frontiers in immunology, 12, 747387.
  • Garcia, A. M., Bishop, E, Li, D, Jeffery, L, Garten, A, Thakker, A, Certo, M, Mauro, C, Tennant, D. A., Dimeloe, S, Evelo, C. T., Coort, S. L. and Hewison, M. (2021) 'Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis', The Journal of Steroid Biochemistry and Molecular Biology, 211, 105891.
  • Kucuk, S, Niven, J, Caamano, J, Jones, S, Camacho-muñoz, D, Nicolaou, A. and Mauro, C. (2021) 'Unwrapping the mechanisms of ceramide and fatty acid-initiated signals leading to immune-inflammatory responses in obesity', The International Journal of Biochemistry & Cell Biology, 135, 105972.
  • Ko, J-H, Olona, A, Papathanassiu, A. E., Buang, N, Park, K-S, Costa, A. S. H., Mauro, C, Frezza, C. and Behmoaras, J. (2020) 'BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages', Journal of Cell Science, 133(22). 
  • Certo, M, Tsai, C-H, Pucino, V, Ho, P-C. and Mauro, C. (2020) 'Lactate modulation of immune responses in inflammatory versus tumour microenvironments', Nature Reviews Immunology.
  • Farah, H, Young, S, Mauro, C. and Jones, S. (2020) 'Metabolic dysfunction and inflammatory disease: The role of stromal fibroblasts', The FEBS journal. 
  • Cheung, K. C. P., Fanti, S, Mauro, C, Wang, G, Nair, A. S., Fu, H, Angeletti, S, Spoto, S, Fogolari, M, Romano, F, Aksentijevic, D, Liu, W, Li, B, Cheng, L, Jiang, L, Vuononvirta, J, Poobalasingam, T. R., Smith, D. M., Ciccozzi, M, Solito, E. and Marelli-Berg, F.M. (2020) 'Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming', Nature Communications, 11, 3595.
  • Pucino, V, Certo, M, Bulusu, V, Cucchi, D, Goldmann, K, Pontarini, E, Haas, R, Smith, J, Headland, S. E., Blighe, K, Ruscica, M, Humby, F, Lewis, M. J., Kamphorst, J. J., Bombardieri, M, Pitzalis, C. and Mauro, C. (2019) 'Lactate buildup at the site of chronic inflammation promotes disease by inducing CD4+ T cell metabolic rewiring', Cell Metabolism, 30(6), 1055-1074.e8.
  • Cucchi, D, Camacho-muñoz, D, Certo, M, Niven, J, Smith, J, Nicolaou, A. and Mauro, C. (2019) 'Omega-3 polyunsaturated fatty acids impinge on CD4+ T cell motility and adipose tissue distribution via direct and lipid mediator-dependent effects', Cardiovascular Research, 116(5), pp.1006-1020. 

Inflammatory mechanisms that drive degenerative joint pathology in osteoarthritis

  • Mellors, B, Allen, P, Lavecchia, C.E., Mountcastle, S, Cooke, M.E., Lawless, B.M., Cox, S.C., Jones, S, and Espino, D.M. (2023) 'Development and experimental validation of a dynamic numerical model for human articular cartilage', Proc Inst Mech Eng H, 237(7):879-889. doi: 10.1177/09544119231180901.
  • Wijesinghe, S.N., Badoume, A, Nanus, D.E., Sharma-Oates, A, Farah, H, Certo, M, Alnajjar, F, Davis, E.T., Mauro, C, Lindsay, M.A., and Jones, S.W. (2023) 'Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets', Clin Transl Med., 13(4):e1232. doi: 10.1002/ctm2.1232. 
  • Nicholson, T.A., Sagmeister, M, Wijesinghe, S.N., Farah, H, Hardy, R.S., and Jones, S.W. (2023) 'Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges', Pharmaceutics, 15(1), 237. https://doi.org/10.3390/pharmaceutics15010237. 
  • Edwards, S.J., Carter, S, Nicholson, T, Allen, S.L., Morgan, P.T., Jones, S.W., Rendeiro, C, and Breen, L. (2022) 'Epicatechin and its colonic metabolite hippuric acid protect against dexamethasone-induced atrophy in skeletal muscle cells', The Journal of Nutritional Biochemistry, 1;110:109150.
  • Simou, K, Jones, S.W., Davis, E.T., Preece, J, and Zhang, Z.J. (2022) 'Rheological and interface adhesive properties of osteoarthritic synovial fluids', Biotribology, 1;32:100227.
  • Wijesinghe, S.N., Anderson, J, Brown, T.J., Nanus, D.E., Housmans, B, Green, J.A., Hackl, M, Choi, K.K., Arkill, K.P., Welting, T, James, V, Jones, S.W., and Peffers, M.J. (2022) 'The role of extracellular vesicle miRNAs and tRNAs in synovial fibroblast senescence', Frontiers in Molecular Biosciences, 23;9.
  • Nicholson, T, Davis, L, Davis, E.T., Newton Ede, M, Scott, A, and Jones, S.W. (2022) 'e-Cigarette Vapour Condensate Reduces Viability and Impairs Function of Human Osteoblasts, in Part, via a Nicotine Dependent Mechanism',  Toxics, 10(9), 506.
  • Fenton, C.G., Crastin, A, Martin, C.S., Suresh, S, Montagna, I, Hussain, B, Naylor, A.J., Jones, S.W., Hansen, M.S., Gorvin, C.M., and Price, M. (2022) '11β-Hydroxysteroid Dehydrogenase Type 1 within Osteoclasts Mediates the Bone Protective Properties of Therapeutic Corticosteroids in Chronic Inflammation', International Journal of Molecular Sciences, 30;23(13):7334.
  • Farah, H, Wijesinghe, S.N., Nicholson, T, Alnajjar, F, Certo, M, Alghamdi, A, Davis, E.T., Young, S.P., Mauro, C, and Jones, S.W. (2022) 'Differential metabotypes in synovial fibroblasts and synovial fluid in hip osteoarthritis patients support inflammatory responses', International Journal of Molecular Sciences, 17;23(6):3266.
  • Wijesinghe, S.N., Lindsay, M.A., and Jones, S.W. (2022) 'Long Non-coding RNAs in Rheumatology. Long Noncoding RNA: Mechanistic Insights and Roles in Inflammation', Cham: Springer International Publishing, pp. 35-70.
  • Nanus, D. E., Badoume, A, Wijesinghe, S. N., Halsey, A. M., Hurley, P, Ahmed, Z, Botchu, R, Davis, E. T., Lindsay, M. A., and Jones, S. W. (2021) 'Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets', eBioMedicine, 72:103618. https://doi.org/10.1016/j.ebiom.2021.103618.
  • Wijesinghe, S. N., Lindsay, M. A., and Jones, S. W. (2021) 'Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review', Biomedicines, 9(8), 902. https://doi.org/10.3390/biomedicines9080902.
  • Philp, A. M., Butterworth, S, Davis, E. T., and Jones, S. W. (2021) 'eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation', International journal of molecular sciences, 22(13), 6719. https://doi.org/10.3390/ijms22136719.
  • Alnajjar, F. A., Sharma-Oates, A, Wijesinghe, S. N., Farah, H, Nanus, D. E., Nicholson, T, Davis, E. T., and Jones, S. W. (2021) 'The Expression and Function of Metastases Associated Lung Adenocarcinoma Transcript-1 Long Non-Coding RNA in Subchondral Bone and Osteoblasts from Patients with Osteoarthritis', Cells, 10(4), 786. https://doi.org/10.3390/cells10040786.
  • Nicholson, T, Scott, A, Newton Ede, M, and Jones, S. W. (2021) 'Do E-cigarettes and vaping have a lower risk of osteoporosis, nonunion, and infection than tobacco smoking?', Bone & joint research, 10(3), 188–191. https://doi.org/10.1302/2046-3758.103.BJR-2020-0327.R1.
  • Wilhelmsen, A, Tsintzas, K, and Jones, S. W. (2021) 'Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing', GeroScience, 43(1), 85–110. https://doi.org/10.1007/s11357-021-00322-4.
  • Farah, H, Young, S. P., Mauro, C, and Jones, S. W. (2021) 'Metabolic dysfunction and inflammatory disease: the role of stromal fibroblasts', The FEBS journal, 288(19), 5555–5568. https://doi.org/10.1111/febs.15644.
  • Wijesinghe, S. N., Nicholson, T, Tsintzas, K, and Jones, S. W. (2021) 'Involvements of long noncoding RNAs in obesity-associated inflammatory diseases', Obesity reviews: an official journal of the International Association for the Study of Obesity, 22(4), e13156. https://doi.org/10.1111/obr.13156.
  • Nicholson, T, Scott, A, Newton Ede, M, and Jones, S. W. (2021) 'The impact of E-cigarette vaping and vapour constituents on bone health', Journal of inflammation, 18(1), 16. https://doi.org/10.1186/s12950-021-00283-7.
  • Pandey, P. R., Yang, J. H., Tsitsipatis, D, Panda, A. C., Noh, J. H., Kim, K. M., Munk, R, Nicholson, T, Hanniford, D, Argibay, D, Yang, X, Martindale, J. L., Chang, M. W., Jones, S. W., Hernando, E, Sen, P, De, S, Abdelmohsen, K, and Gorospe, M. (2020) 'circSamd4 represses myogenic transcriptional activity of PUR proteins', Nucleic acids research, 48(7), 3789–3805. https://doi.org/10.1093/nar/gkaa035.
  • Nanus, D. E., Wijesinghe, S. N., Pearson, M. J., Hadjicharalambous, M. R., Rosser, A, Davis, E. T., Lindsay, M. A., and Jones, S. W. (2020) 'Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis-Associated Lung Adenocarcinoma Transcript 1 Long Noncoding RNA in Obese Patients With Osteoarthritis', Arthritis & Rheumatology, 72(4), 609–619. https://doi.org/10.1002/art.41158.
  • Anderson, J. R., Phelan, M. M., Rubio-Martinez, L. M., Fitzgerald, M. M., Jones, S. W., Clegg, P. D., and Peffers, M. J. (2020) 'Optimization of Synovial Fluid Collection and Processing for NMR Metabolomics and LC-MS/MS Proteomics', Journal of proteome research, 19(7), 2585–2597. https://doi.org/10.1021/acs.jproteome.0c00035. 
  • Pearson, M. J., Philp, A. M., Haq, H, Cooke, M. E., Nicholson, T, Grover, L. M., Newton Ede, M, and Jones, S. W. (2019) 'Evidence of Intrinsic Impairment of Osteoblast Phenotype at the Curve Apex in Girls With Adolescent Idiopathic Scoliosis', Spine deformity, 7(4), 533–542. https://doi.org/10.1016/j.jspd.2018.11.016.
  • Davies, O. G., Cox, S. C., Azoidis, I, McGuinness, A, Cooke, M, Heaney, L. M., Davis, E. T., Jones, S. W., and Grover, L. M. (2019) 'Osteoblast-Derived Vesicle Protein Content Is Temporally Regulated During Osteogenesis: Implications for Regenerative Therapies', Frontiers in bioengineering and biotechnology, 7, 392. https://doi.org/10.3389/fbioe.2019.00392.
  • Nicholson, T, Church, C, Tsintzas, K, Jones, R, Breen, L, Davis, E. T., Baker, D. J., and Jones, S. W. (2019) 'Vaspin promotes insulin sensitivity of elderly muscle and is upregulated in obesity', The Journal of endocrinology, JOE-18-0528.R3. Advance online publication. https://doi.org/10.1530/JOE-18-0528.
  • Mountcastle, S. E., Allen, P, Mellors, B, Lawless, B. M., Cooke, M. E., Lavecchia, C. E., Fell, N, Espino, D. M., Jones, S. W., and Cox, S. C. (2019) 'Dynamic viscoelastic characterisation of human osteochondral tissue: understanding the effect of the cartilage-bone interface', BMC musculoskeletal disorders, 20(1), 575. https://doi.org/10.1186/s12891-019-2959-4.
  • Hurley, P, Alnajjar, F, Wijesinghe, S, Nanus, D. E., Davis, E. T., and Jones, S. W. (2019) 'The combination of local infiltration analgesia reagents increases their detrimental effect on human hip OA patient osteoblast viability and function', Journal of orthopaedics, 16(5), 434–439. https://doi.org/10.1016/j.jor.2019.06.014.
  • Murphy, D. P., Nicholson, T, Jones, S. W., and O'Leary, M. F. (2019) 'MyoCount: a software tool for the automated quantification of myotube surface area and nuclear fusion index', Wellcome open research, 4:6. https://doi.org/10.12688/wellcomeopenres.15055.1.
  • Macfadyen, M. A., Daniel, Z, Kelly, S, Parr, T, Brameld, J. M., Murton, A. J., and Jones, S. W. (2019) 'The commercial pig as a model of spontaneously-occurring osteoarthritis', BMC musculoskeletal disorders, 20(1), 70. https://doi.org/10.1186/s12891-019-2452-0.
  • O'Leary, M. F., Wallace, G. R., Davis, E. T., Murphy, D. P., Nicholson, T, Bennett, A. J., Tsintzas, K, and Jones, S. W. (2018) 'Obese subcutaneous adipose tissue impairs human myogenesis, particularly in old skeletal muscle, via resistin-mediated activation of NFκB', Scientific reports, 8(1), 15360. https://doi.org/10.1038/s41598-018-33840-x.
  • Cooke, M. E., Lawless, B. M., Jones, S. W., and Grover, L. M. (2018) 'Matrix degradation in osteoarthritis primes the superficial region of cartilage for mechanical damage', Acta biomaterialia, 78, 320–328. https://doi.org/10.1016/j.actbio.2018.07.037.
  • Nicholson, T, Church, C, Baker, D. J., and Jones, S. W. (2018) 'The role of adipokines in skeletal muscle inflammation and insulin sensitivity', Journal of inflammation, 15, 9. https://doi.org/10.1186/s12950-018-0185-8.
  • Cooke, M. E., Jones, S. W., Ter Horst, B, Moiemen, N, Snow, M, Chouhan, G, Hill, L. J., Esmaeli, M, Moakes, R, Holton, J, Nandra, R, Williams, R. L., Smith, A. M., and Grover, L. M. (2018) 'Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications', Advanced materials, 30(14), e1705013. https://doi.org/10.1002/adma.201705013.
  • Majumdar, T, Cooke, M. E., Lawless, B. M., Bellier, F, Hughes, E, Grover, L. M., Jones, S. W., and Cox, S. C. (2018) 'Formulation and viscoelasticity of mineralised hydrogels for use in bone-cartilage interfacial reconstruction', Journal of the mechanical behavior of biomedical materials, 80, 33–41. https://doi.org/10.1016/j.jmbbm.2018.01.016. 

 

Ageing mechanisms and delirium

  • de Magalhães, J.P. (2023) 'Ageing as a software design flaw', Genome Biol., 24, 51.https://doi.org/10.1186/s13059-023-02888-y. 
  • Vega-Magdaleno, G.D., Bespalov, V, Zheng, Y, Freitas, A, and de Magalhães, J.P. (2022) 'Machine-learning-based predictions of caloric restriction associations across ageing-related genes', BMC Bioinformatics, 23:10. https://doi.org/10.1186/s12859-021-04523-8. 
  • Palmer, D, Fabris, F, Doherty, A, Freitas, A.A., and de Magalhães, J.P. (2021) 'Ageing transcriptome meta-analysis reveals similarities and differences between key mammalian tissues', Aging, 13(3), 3313-3341. https://doi.org/10.18632/aging.202648. 
  • Avelar, R.A., Ortega, J.G., Tacutu, R, Tyler, E, Bennett, D, Binetti, P, Budovsky, A, Chatsirisupachai, K, Johnson, E, Murray, A, Shields, S, Tejada-Martinez, D, Thornton, D, Fraifeld, V.E., Bishop, C, and de Magalhães, J.P. (2020) 'A multidimensional systems biology analysis of cellular senescence in aging and disease', Genome Biology, 21(1), 91. https://doi.org/10.1186/s13059-020-01990-9.
  • Chatsirisupachai, K, Palmer, D, Ferreira, S, and de Magalhães, J.P. (2019) 'A human tissue‐specific transcriptomic analysis reveals a complex relationship between aging, cancer, and cellular senescence', Aging Cell, 18(6), e13041. https://doi.org/10.1111/acel.13041. 

For a full list of publications, please visit the Rejuvenomics Lab Publications website. 

Mitochondrial ageing and diabetes

  • Publications coming soon

Grants

  • 2023-2028, BHF Senior Fellowship, £1,200,00

Project: Project: Investigating and exploiting lactate signalling in athero-immunometabolism (Lead investigator: Claudio Mauro).

  • 2022-2027, NIHR Birmingham BRC in Inflammation, £1,726,000 

Project: Sarcopenia and Multimorbidity (Principal investigator: Janet Lord). 

  • 2022-2025, MRC UKRI, £1,322,218

Project:  MICA: Synovial fibroblast pain pathotypes: A roadmap to understanding and targeting the complexity of patient-reported joint pain in osteoarthritis (Lead investigator: Simon Jones).

  • 2022-2024, MRC-BBSRC Ageing Network, £211,530

Project: Food for added life years: Putting research into action (Co-investigator: Niharika Duggal).

  • 2022-2024,  BBSRC, £200,000

Project: Establishing a network to catalyse collaboration for reducing immune ageing (CARINA) (Co-investigator: Janet Lord).

  • 2022 - 2024, National Institute for Health Research, £249,927

Project: WHiTE-DECI: World Hip Trauma Evaluation – Delirium and Cognitive Impairment; a randomised feasibility trial comparing severity of delirium symptomatology between hip fracture patients 60 years and over treated with a peri-operative infusion of anti-TNF or placebo (Co-investigator: Thomas Jackson).

  • 2022-2023, Scar Free Foundation, £120,000

Project: Does major trauma accelerate the ageing process and can it be alleviated by physical activity? (Lead investigator: Janet Lord).

  • 2021-2024, NADACE Europe, £310,000

Project: Comparing the Phenotypes and Trajectories of Human Ageing Associated with Exercise or Inactivity: with a particular focus on the biology of skeletal muscle and the immune system (Principal investigator: Janet Lord).

  • 2021 – 2024, National Institute for Health Research, £2,495,158

Project: OPTIMising therapies, disease trajectories, and AI assisted clinical management for patients Living with complex multimorbidity (OPTIMAL study) (Lead investigator: Thomas Jackson).

  • 2021-2023, Bayer Consumer Care, £482,213

Project: An uncontrolled open label trial of a nutritional supplement to reduce biological and immune ageing in healthy older people (Alphaville) (Principal investigators: Thomas Jackson and Janet Lord)

  • 2021-2023, Academy of Medical Sciences (Springboard Award), £100,000

Project: Gut microbiome dysbiosis and immune ageing: investigating associations and potential for novel therapies (Lead investigator: Niharika Duggal).

  • 2021-2023, Academy of Medical Sciences (Newton Fellowship), £99,000

Project: Understanding the influence of physical activity on ageing processes (Lead investigator:  Amanda Sardeli).

  • 2020-2023, MRC Research Grant, £591,000

Project: Lactate as an inflammatory early signal in ectopic lymphoid neogenesis and its translational impact in patients with autoimmune diseases (Lead investigator: Claudio Mauro).

  • 2020-2023, M . BHF PhD studentship, £107,000

Project: Measurement of EV in cardiovascular disease using a novel interferometric method (Lead supervisors: Paul Harrison and Thomas Jackson)

  • 2020-2022, Marie-Curie Fellowship, €225,000

Project: Dissecting the impact of lactate in tuberculosis (Lead investigator: Alba Llibre).

  • 2018-2022, Versus Arthritis, £201,248

Project: Obesity-associated joint inflammation in patients with osteoarthritis: The role of long non-coding RNAs (Lead investigator: Simon Jones).

  • 2017-2023, MRC-Versus Arthritis, £2,000,000

Project: Centre for Musculoskeletal Ageing Research (Principal investigator: Janet Lord).

  • 2017-2022, Versus Arthritis, £228,668

Project: Are synovitis-associated lncRNAs central regulators of inflammatory pain in patients with knee OA: A route to identifying a novel analgesic drug for OA patients (Lead investigator: Simon Jones).

Our patient partnerships

Title

Clinical Trial ID/IRAS

Patient Cohort

Skeletal muscle/adipose cross-talk: novel modulators of OA joint inflammation

IRAS 206880

1000 patients with end-stage osteoarthritis of the knee, hip, hand, shoulder, elbow, foot

 Inflammation and OA joint pain

IRAS 228205

41 patients with early osteoarthritis; 41 patients with end-stage knee osteoarthritis

Intrinsic differences at the curve apex in adolescent idiopathic scoliosis

IRAS 256224

22 patient with adolescent idiopathic scoliosis

Evaluation of Mechanisms of Sarcopaenia in Chronic Inflammatory Disease (Chronic Liver Disease, Inflammatory Arthritis and Inflammatory Bowel Disease) pre- and post-standard of care intervention; an observational study

IRAS 238190

150 patients with chronic inflammatory disease: Rheumatoid arthritis, Chronic liver disease, Inflammatory bowel disease

Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI 2)

 

200 burns patients with longitudinal sampling from day 1 after injury to 1 year

Birmingham 1000 Elders

  

>600 healthy older adults aged 60 and over who support ageing research.

Investigating the role of lactate during Mycobacterium tuberculosis infection

IRAS 278536

50 individuals with latent Mycobacterium tuberculosis infection and 50 with active tuberculosis disease