Beyond the Absence of

Disease

John Beard
Recent frameworks for thinking about aging
and health
National Academy of Medicine 2021

WHO 2015
 But after just a few years……
The science is advancing so quickly that it is starting
to challenge the way we think about health itself:
• Geroscience
Hallmarks of Aging

Lopez Otin C et al..

Cell, 2023
 Now
The science is rapidly advancing to now question the
very way we think about health:
• Geroscience
• Complex systems
Complex systems

Image: Perito Moreno

Complex systems
Complex systems
 Now
The science is rapidly advancing to now question the
very way we think about health:
• Geroscience
• Complex systems
• Big data and AI
Prevalence of chronic disease

Harris RE, 2013

 Chronic disease
Chronic
disease
expression

Symptom
Threshold

Age
 Chronic disease
Chronic
disease
expression

Symptom
Threshold

Age
 Chronic disease
Chronic
disease
expression

Symptom
Threshold

Age
 Chronic disease
Chronic
disease
expression

Symptom
Threshold

Age
 Chronic disease
Chronic
disease
expression

Symptom
Threshold

Age
 Chronic disease
Chronic
disease
expression

Symptom
Threshold

Age
 Chronic disease
Chronic
disease
expression

Symptom
Threshold

Age
Recent frameworks for thinking about aging
and health

Ferrucci et al. Circ Resp 2018

 A functional framing of health and ageing

Framed around the

functional ability that
enables people to be
and do the things
they value.
What are the things older people want to
be and do?

20
Capacity across the life course

Increasing age group

There is no such thing as a typical older person

65 and above

Increasing age group

Capacity across the life course

Increasing age group

Capacity across the life course

Increasing age group

Capacity across the life course

Increasing age group

 Capacity across the life course

Early
Prenatal Develop- Maturation Robust and stable Age-related declines
ment

Significant losses

Mean Capacity

Increasing age group

 Life course opportunities for intervention

Early
Prenatal Develop- Maturation Robust and stable Age-related declines
ment

Interventions to foster ability

v Significant losses
Interventions to foster resilience and capacity

Mean Capacity

Increasing age group

Agefriendlyworld.org
 Measuring intrinsic capacity

All the individual level attributes

that contribute to functional ability
 Problems with current functional measures

• Actually disease-based (Global Burden of Disease

DALYs, HALE, YLD)
• Domain specific (e.g. cognitive)
• Categorical (e.g. frailty)
• Severe losses (e.g. Activities of Daily Living)
• Fail to distinguish between the contribution of the
environment and that of the individual
(Instrumental Activities of Daily Living)
 High Life Expectancy Countries in
HRS Family

HRS ELSA CHARLS SHARE

US UK China Austria Belgium Czech Denmark France
Participants 25,726 18,813 12,740 2,553 6,002 2,612 1,750 2,105
Waves 14 9 4 8 8 7 8 8
Ages (years) ≥51 ≥50 ≥45 ≥50 ≥50 ≥50 ≥50 ≥50
Commenced 1992 1998 2011 2004 2004 2006 2004 2004

SHARE

Germany Greece Israel Italy Netherlands Portugal Slovenia Spain Sweden Switzerland

Participants 3,423 2,883 2,585 3,209 3,174 2,168 3,779 3,302 3,964 1,605

Waves 8 6 6 8 8 4 5 8 8 8

Ages (years) ≥50 ≥50 ≥50 ≥50 ≥50 ≥50 ≥50 ≥50 ≥50 ≥50

Commenced 2004 2004 2005 2004 2004 2011 2011 2004 2004 2004
 Bifactor CFA

ELSA

Beard JR, Jotheeswaran AT,

Cesari M, et al. BMJ Open
2019
 Direct and indirect effects of
characteristics on loss of IADLs in Wave 2

ELSA

Beard JR et al. BMJ Open 2019

 Intrinsic Capacity

Locomotor Cognitive Sensory Psychological Other

Expressed
Capacities

Vitality/
DNA Integrity Proteostasis Glycans
• Nuclear Stem cell
Resilience
• Mitochondrial exhaustion
Cellular
senescence/SASP
Intercellular
Epigenetic communication
changes (pro-inflammatory
(Methylation) Microbiome mediators)

Genetic inheritance

Beard JR, Si Y, Liu Z, Chenoweth L, Hanewald K.

Journals of Gerontology Series A: Biomedical Sciences
and Medical Sciences. 2022
 Capacity across the life course

Early
Prenatal Develop- Maturing Age-related declines
ment ation

Significant losses

Mean Overt
Capacity

Mean
Vitality/Resilience

Increasing age group

Intrinsic capacity by age

Beard JR, Chen M J Nut Health Aging 2023

Relationship between capacity and SES
in SHARE
Variation of intrinsic capacity between
setting
Intrinsic capacity summary score by chronic
health conditions and age-group

Beard JR et al. BMJ Open 2019

Intrinsic capacity summary score by chronic
health conditions and age-group

Beard JR et al. BMJ Open 2019

 Linking early-life factors with late-life intrinsic,
cognitive and sensory capacities, China, 2011–2013

Si Y et al. Bull World Health Organ 2023

 Cohort trends in Intrinsic Capacity in ELSA
intrinsic_capacity psychological locomotor
.5

.5

.5
Mean factor score

Mean factor score

Mean factor score

0

0
-.5

-.5

-.5
-1

-1

-1
-1.5

-1.5

-1.5
60 65 70 75 80 85 90 60 65 70 75 80 85 90 60 65 70 75 80 85 90
Age Age Age

vitality cognition sensory

.5

.5
.5
Mean factor score

Mean factor score

Mean factor score

0

0
0
-.5

-.5
-.5
-1

-1
-1
-1.5

-1.5

-1.5
60 65 70 75 80 85 90 60 65 70 75 80 85 90 60 65 70 75 80 85 90
Age Age Age

1920 1930 1940 1950

 Functional outcomes: possibilities

• Public health/epidemiology
– Behavioral risk factors
– Stratification, comparison between interventions
• Meaningful clinical/research endpoints (ICD
code MG2A)
– Health system funding mechanisms
• Better characterise relationship of overt
capacities with biological changes
– The real outcome for geroscience
 Collaborators

World Health Organization University College London

Matteo Cesari, Moreno, Dario
Islene Araujo de Carvalho,
Jotheeswaran
Amuthavalli Thiyagarajan University of New South Wales
Yafei Si,
Katja Hanewald,
Shu Chen,
Toulouse University Hospital Bingqin Li,
Kelly Virecoulon Giudici, Hazel Bateman
Philipe de Souto Barreto, Zhixin Liu,
Christelle Cantet, Lynn Chenoweth
Yves Rolland,
Sandrine Andrieu,
Bruno Vellas
Mailman School PH
Yuan Zhang
Ying Wei
Science of Health
Columbia Aging Center
 Intrinsic Capacity buts……………….

• No validated instrument
• Still unclear conceptualization (e.g. personality
traits, knowledge, vitality, other)
• What about the life course?
• Language (e.g. resilience, reserves)
• Functional ability
Decomposing the life-course inequalities in
intrinsic capacity, China, 2011–2013

Si Y et al. Bull World Health Organ 2023

Enabling communities to look after themselves
 Early
Prenatal Develop- Maturing Robust and stable Age-related declines
ment

Significant losses

Mean Capacity

Mean Resilience

Increasing age group

 Early
Prenatal Develop- Maturing Robust and stable Age-related declines
ment

Significant losses

Mean Capacity

Mean Resilience

Increasing age group

 Width
Recovery
Depth

Robustness = D
Resilience = W+R
 Why do we need to move on
from a disease-based paradigm?

• Reinforce segmented models of health care

• Disjointedness makes it difficult to build a coherent
policy response
• Does not align with older people’s understanding
of health
• Life is about continuums