Vitamins and Antioxidants implication in frailty prevention Tamas - PowerPoint PPT Presentation

Vitamins and Antioxidants implication in frailty prevention Tamas Fulop M.D., PhD Université de Sherbrooke

CONFLICT OF INTEREST DISCLOSURE I have the following potential conflict(s) of interest to report - Consultation fee from Eisai and Co, Japan

Definition of frailty There is no universally accepted definition of frailty : • Depends on whether we consider populations, individuals, research, clinical levels. What is agreed by most: • A geriatric syndrome: multifactorial • cumulative declines and decreased reserves in multiple physiological and organ systems: homeostenosis. • physiologic dysregulation involves multi-organ systems including the musculoskeletal, immune , endocrine, hematologic, and cardiovascular systems: the sum is more important than the nature of each • Results in vulnerability to adverse outcomes: e.g. Falls, death, dependence • Triggered or revealed by minor stressor events, stimuli • Age plays the major role: prevalence  with age

Loss of function

Graphic showing the difference between successful aging and frailty http://www.clinicalgeriatrics.com/article/frailty-multimorbidity-elderly-shift-management-approach#sthash.IfxmHZiW.dpuf

Operationalization/Diagnosis of frailty • The most used criteria to characterize the phenotype of frailty as clinical syndrome are:* : – Loss of wait: self reported – Weakness: grip strength – Exhaustion: self reported – Slowed walking speed: measure of walk speed – Low physical activity: self reported Frailty : presence of at least 3 of these 5 characteristics • Fried, Tangen, Walston et coll., J Ger Med Sci , 2001  The cumulative frailty index (accumulation of deficits):* - disability, - diseases, - physical and cognitive impairments, - psychosocial risk factors, and - Geriatric syndromes (eg, falls, delirium, and urinary incontinence) *Mitnitski AB, et al. Scientific World Journal 2001;1:323 – 36.

Clegg et al, Lancet 2013, 381:752

Fried ried's 's scien scientifi tific c exp xplana lanation tion of of th the c e cycle of le of fr frailty ailty http://www.hopkinsmedicine.org/hmn/s02/feature.

Kanapuru and Erschler, Am J Med. 2009, 122:605

Pathophysiologic Model for Adverse Outcomes in Older Adults Triggers Physiology Outcomes Aging  Free radicals Senescent cells CRP Shortened telomeres IL-6 Activation of Anorexia ? DNA damage Inflammation Frailty Anemia Disability Sarcopenia Disease Osteoporosis Gene Variation IL-6 DHEA-S Cortisol Hyperglycemia Death  Clotting Neuroendocrine Disease Dysregulation IGF-1 Depression DHEA-S Cortisol Cancer Chronic Infection Cardiovascular disease Diabetes/Obesity Modified after Walston et coll., 2006

IL-6 and Multisystem Dysregulation  Lean body mass Anemia Polyclonal expression & IL-6 autoantibodies Osteoporosis HPA axis activation Localized CNS inflammation

Frailty and inflammation/immune-aging markers IL-6  ASSOCIATED to atherosclerosis, osteoporosis, sarcopenia to functional decline and all cause mortality  PREDICTING steeper functional decline during a follow up of 3.5 years (Ferucci et al, JAGS, 2002, 50:1941) measured by:  decreased muscle strength and power and slowed walking speed  two central components of the frailty syndrome.  In Vitro: PBMC stimulated by LPS produced higher IL-6 in frail than Non-frail community dwelling subjects  IL-6 levels: independently associated with frailty

Rutenberg, A.D., Experimental Gerontology (2017), http://dx.doi.org/10.1016/j.exger.2017.08.027

Putative alterations of major biological parameters AGING FRAILTY LOW GRADE INFLAMMATION HIGH GRADE INFLAMMATION NO LIPID ALTERATIONS LIPID ALTERATIONS IMMUNE RESPONSE:  IMMUNE RESPONSE:    HORMONES: LOW HORMONES: VERY LOW NO ANEMIA ANEMIA NO NUTRITIONAL ALTERATIONS NUTRTITIONAL ALTERATIONS CHRONIC VIRAL INFECTION+(?) CHRONIC VIRAL INFECTION++(?) Aging Aging+ + syndr syndrome ome (=b (=biolo iologi gical cal age) ge) Fulop et al. 2010

The etiology and progression of clinical frailty in the older adult Heuberger RA, JNGG, 2011, 30:315

Dorner et al. The Journal of Nutrition, Health & Aging; Volume 18, Number 3, 2014; 264

The immune system and oxi-inflamm-ageing Frailty M.E. Bauer, M.D.l. Fuente / Mechanisms of Ageing and Development 158 (2016) 27 – 37

P. Soysal et al. / Maturitas 99 (2017) 66 – 72

Grouped-time Multivariate Cox Proportional Hazard Models for Demographic and Health Characteristics and Incidence of Severe Walking Disability in the Women’s Health and Aging Study I (N = 545) Oxidative parameters increased in frailty!!! Semba et al. Am J Med. 2007 Dec; 120(12): 1084 – 1089.

Nutrition du sujet âgé, Université Médicale virtuelle francophone

P. Soysal et al. / Maturitas 99 (2017) 66 – 72

Age Age- and and se sex-adjusted adjusted le levels els of of vi vitamin tamin E acc accor ording ding to to fr frail ailty ty sta status. T tus. The unit he unit of of measur measure e for or vi vitamin tamin E (y a (y axis) is xis) is μmol /L /L Ble et al. Journal of Gerontology: MEDICAL SCIENCES, 2006, Vol. 61A, No. 3, 278 – 283

AA is at the crossroads of biological aging, intercepting immunosenescence, inflamm-aging, and oxidative stress (free radical theory of aging), with a potential role in the onset of age- related diseases and frailty trajectories Monacelli et al. Nutrients 2017, 9, 670

* * * * * Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600 – 607 WHAS I study: women 70-80 years: n=754

Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600 – 607

Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600 – 607

* * Independently of the adjusted model the OR, was always higher for those with low micronutrient concentrations Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600 – 607

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Semba et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 594 – 599

From 463 studied 205 became frail Semba et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 594 – 599

Semba et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 594 – 599

Dokuzlar et al. North Clin Istanb 2017;4(1):22 – 28

Bartali et al. Arch Intern Med. 2006 November 27; 166(21): 2335 – 2340

Bartali et al. Arch Intern Med. 2006 November 27; 166(21): 2335 – 2340

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

How does sarcopenia develop in older patients and how is it best managed? http://www.arthritis-rheumatism.com/the-rheuma-muse/sarcopaenia /

Comparison Comparison of of the the fr frequ equenc ency y of of sar sarcop copenia enia and and dyna dynapen penia ia in t in the he pa patients tients acc accor ording ding to vi to vitamin tamin B12 B12 le levels els Bulut et al. Exp. Ger. 2017, 95, 136

Welsh AA. Proceedings of the Nutrition Society (2014), 73, 16 – 33

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Mediterranean Diet Adherence Screener (MEDAS) score and the Mediterranean Diet Score, L.M. León-Muñoz et al. / JAMDA 15 (2014) 899e903 also known as the Trichopoulou index

Ng et al. The American Journal of Medicine, Vol 128, No 11, November 2015; 1225