U N I V E R S I T Ä T S M E D I Z I N B E R L I N

Gender in Aging

Ursula Müller-Werdan,Chair of Geriatrics,

Charité – Universitätsmedizin Berlin,Ev. Geriatriezentrum Berlin

International Congress on Gender Medicine, Charité – Berlin, 23 September 2015

Classification of age

⇒“yound old“ ≥ 65 years

⇒“old old“ ≥ 75 years

⇒“oldest old“ ≥ 85 years

• In the last century:

Progressive increase

⇒ Portion of “young old“, “old old“ and “oldest old“ individuals

⇒ In the industrialised nations the most rapidly growing population is the age group over 65

Overallrank

Country Overall lifeexpectancy

Male lifeexpectancy

Malerank

Female lifeexpectancy

Femalerank

1 Japan 87 85 1 87.3 22 Andorra 84.2 80.8 8 87.6 13 Singapore 84 82 2 87 34 Hong Kong 83.8 82 2 85.6 55 San Marino 83.5 82 2 85 116 Iceland 83.3 81.4 5 85.2 97 Italy 83.1 80.4 10 85.8 48 Sweden 83 81.4 5 84.6 139 Australia 83 80.5 9 85.5 610 Switzerland 82.8 80.4 10 85.4 711 Canada 82.5 80.4 10 84.6 1312 Spain 82.5 79.5 15 85 1113 New Zealand 82.1 80.2 19 84 1914 Luxembourg 82 79.5 15 84.5 1514 Israel 82 80 14 84 1915 Norway 81.9 80.2 13 83.6 2216 Austria 81.5 78.5 24 84.5 1517 France 81.5 78 19 85 918 Netherlands 81.5 79.5 15 83.5 2519 Ireland 81.4 79.2 22 83.6 2220 Cyprus 81.2 79.1 23 84.3 1821 Chile 81.2 80.1 38 82.3 3322 Germany 81 78.5 24 83.5 2523 Greece 81 78 28 84 1924 Finland 81 78 0 28 84 19

http://en.wikipedia.org/wiki/List_of_countries_by_life_expectancy

WHO 2012

Age and functional status

Modified from: Meisel M, Dessau

ever reached by a human being:

122 years and 164 days

Jeanne Louise Calment* 21.02.1875† 04.08.1997

The highest age documented

http://www.supercentenarian.com/records.html

“Aging“?

Definition:

The collection of changes that render human beings progressively more likely to die

Medawar 1952

“Mortality: Hallmark of Ageing“

Finch CE (1990) Longevity, Senescence, and the Genome. The University of Chicago Press, Chicago and London

Gompertz function

http://www.welt.de/gesundheit/article8126817/Jedes-vierte-Maedchen-in-Deutschland-wird-100.html

Sexually dimorphic longevity in humans

SexYears for the those having reached the age of…

At birth 65 70 75 80 85 90 95 100

Male 75.89 16.26 12.83 9.83 7.24 5.19 3.64 2.62 1.95

Femal 81.55 19.77 15.67 11.93 8.64 6.01 4.02 2.80 2.03

Life expectancy related to sex and age

in Germany

Deutsches Zentrum für Altersfragen, Berlin.Basisdaten: Statistisches Bundesamt, Wiesbaden - Fachserie 1: Bevölkerung und Erwerbstätigkeit.Reihe 1.1: Natürliche Bevölkerungsbewegung.

Estimations by the “Max-Planck-Institut für Demographische Forschung“ in Rostock predict that every other girl born now will survive to her

100th birthday

Every other boy born now will at least live to his 95th birthday.

Compression or extension of morbidity?

Fries J (2003) Ann Intern Med 139: 455 - 459 Fries J (1980) N Engl J Med 303: 130 - 139

0 55 76 Jahre

Present state of morbidity

0 55 80 Jahre

Life extension,

extension of morbidity

0 65 81 Jahre

Life extension,

compression of morbidity

Organisms with negligible senescense

http://www.senescence.info/nature.html http://en.wikipedia.org/wiki/Andean_Condor http://www.aquarium-kosmos.de/.../hydra_blau2.jpg

Red sea urchin Galapagos tortoise Andean condor

Hydra

Senescence in mammals

http://images.modhoster.de/system/files/0008/7710/large/Gorilla.jpg

Why senescence?

Ageing, i.e. the intrinsic modulation of the probability of survival, is not necessary to control the size of a population.

Thomas von Zglinicki, Thorsten Nikolaus; In: Schmidt/Thews, Physiologie des Menschen, 30. Auflage

Ageing: an evolutionarily successful strategy

Extrinsic risks mainly determine the length of life and reproduction.

Therefore only limited resources are allocated for maintenance and repair.

Genes controlling repair processes are important for ageing and longevity.

There are no specific genes programming ageing aa a deterministic Process.

Thomas von Zglinicki, Thorsten Nikolaus; In: Schmidt/Thews, Physiologie des Menschen, 30. Auflage

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From: Kleine-Gunk; Deutsches Ärzteblatt 2007; 104:A2054-A2060

Age (years)

Development of hormone levels over lifetime (100 = maximum)

(GH)

E

e

Sex/ gender differences in aging

• Physiology/Biology

• Burden of disease

• Sociology

Lucas Cranach der Ältere, 1533

Sex/ gender differences in aging

• Physiology/Biology

• Burden of disease

• Sociology

Lucas Cranach der Ältere, 1533

Epstein et al; N Engl J Med 1999; 340:1801-1811

Genomic and non genomic effects of estrogens

ER ER -E

ERENucleus

Gene expression

Cytoplasm

Estrogen

Estrogen receptors are ligand activated transcription factors

Nach: Moggs & Orphanides; EMBO reports 2001; 21:775-781

ER -E

CoAct Int

Epstein et al; N Engl J Med 1999; 340:1801-1811

Sexual dimorphism of immune response♦ Autoimmune dieases are more frequently seen in women

(e.g.. SLE, Hashimoto thyroiditis, rheumatoid arthritis)

♦ Women on average have higher plasma antibody levelsthan men

♦ Female mice exhibit a stronger cellular immune responsein sepsis → sepsis is better tolerated

♦ Male mice in hemorrhagic trauma have a worse heartfunction when compard to females, heart funtion in thesemale mice can be improved by castration or testosteron

Angele .... Chaudry; Shock 2000; 14:81-90

Innate immunity Adaptive immunity

Archaic system Evolutionarily more recent

Activation non-specifically Clonal expansion, memory

In senescence: In senescence: preserved/ activated worsened

Physiological ageing of the immune system

Relative abundances of the most abundant bacterial groups on the hand surfaces, with the hand samples divided into categories of sex (A), time since last hand washing (B), and the

dominant versus the nondominant hand (C)

Fierer N. et.al. PNAS 2008;105:17994-17999

©2008 by National Academy of Sciences

Seals und Esler 2000; J Physiol 528.3:407-417

Nerval sympathetic activity Plasma noradrenaline

young old Young old

Nerval sympathetic activity/ Plasma noradrenaline levels

20-year old woman

20-year old man

65-year old woman

65-year old man

Men

Women

Sex/ gender differences in aging

• Physiology/Biology

• Burden of disease

• Sociology

Lucas Cranach der Ältere, 1533

Prevalence of chronic diseases as a function of age (USA 2002-2003)

http://www.senescence.info/definitions.html

• CAD- in-patient morbidity in men twice as high as in women

• Fatalities inischemic heart disease in males only slightly higher than in females („gender paradox“)

• More women than men die from heart failure (2011: 30621 women and 14807 men), valvular disease and arrhythmias

Cardiovasc 2014; 14 (2): 28-30

Marijon E te al; JAMA 2013;310:642-643

Sudden cardiac death at moderate/ high physical activityFrance 2005-2010, 775 fatalities (42 women), Age 15-76

Bicycle riding Jogging Swimming

Incidence men: 10.1 per 1 Million sporting participants per yearIncidence women: 0.51

Sex/ gender differences in aging

• Physiology/Biology

• Burden of disease

• Sociology

Lucas Cranach der Ältere, 1533

BILD Leipzig, 03.04.2012

„Turn-Oma“ Johanna Quaas (88)

Serum-Kreatinin und Kreatinin-Clearance in verschiedenen Lebensphasen

Wehling, Burkhardt: Arzneitherapie für Ältere. Springer 2010

Fleg et al. 1995; J Appl Physiol 78:890-900

Änderung hämodynamischer Parameter im Alter

Baltimore Longitudinal Study of Aging

121 Männer

79 Frauen