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The Journal of Frailty & Aging©
Volume 1, Number 1, 2012
FRAILTY AND AGING
M. CESARI1,2,3
1. Institut du Vieillissement, Université de Toulouse, Toulouse, France; 2. Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; 3. INSERM Unit 1027, Toulouse,
France. Address for correspondence: Matteo Cesari, MD, PhD, Institut du Vieillissement, Université de Toulouse; 37 Allées Jules Guesde, 31000 Toulouse, France;
Phone: +33 (0)5 61145628, Fax: +33 (0)5 61145640, email: macesari@gmail.com
As a geriatrician, I have always been taught to look at
medical issues in a different way, from an alternative
perspective. What is true and well-established in younger adults
becomes arguable and doubtful in the complex older patient.
Such uncertainty is largely at the basis of the long-lasting
“evidence-based medicine” issue which has necessarily
generated an immediate practical sense in geriatrics. With
advancing age, even the importance of the clinical and research
endpoints characteristic of adulthood tends to become weaker.
For example, the mortality outcome may lose most of its
significance when evaluating the efficacy of an intervention in
nonagenarians or centenarians. In fact, any (forcely relative)
extension of survival might easily become misleading if not
sided by a broader evaluation of the effects on the multifaceted
health status (1). In this context, other conditions may appear
more determinant in driving clinical choices, developing
guidelines, and directing research interests in geriatrics. Among
all, disability surely deserves a special spot.
The inability to adequately interact with the surrounding
environment does not only represents a major burden for the
person, but is also associated with relevant public health
expenditures. Paradigmatical are data published some years ago
by Fried and colleagues (2) showing that the 19.6% of
community-dwelling older persons with functional dependence
accounted for almost 50% of total health care expenditures in
the United States. From these figures and taking into account
the epidemiological trends documenting the progressive aging
of our societies, it is natural considering disability as a major
public health issue (3).
Since disability is largely considered as an irreversible
condition (4), the most appropriate way to face it is through
prevention. Thus, it is necessary to implement screening
programs for the early detection of subjects at increased risk of
experiencing disability in the next future, and to develop
interventions specifically targeting the inner foundations of the
disabling cascade. We need to promptly act when disability is
not yet appeared, but the prodromal symptoms and signs start at
being manifest. Such pre-disability condition is commonly
identified with the so-called “frailty syndrome” (5).
Frailty is a state of increased vulnearbility to endogeneous
and exogenous stressors experienced by older persons. It poses
the subject at higher risk of major negative health-related
events, including disability, hospitalization, institutionalization,
Received February 14, 2012
Accepted for publication February 21, 2012
3
and mortality (6). Its detection is important because frailty,
differently from disability, is described as a reversible
condition, thus still amenable of interventions.
The clinical relevance of frailty is obvious. The idea of
detecting subjects at increased risk of adverse outcomes to
preventively act constitutes one of the cornerstones of
medicine. At the same time, it should not be ignored the
important role played by frailty in the research setting. Frail
subjects may represent the ideal candidates to test interventions
aimed at preventing negative events (e.g., onset of disability).
Their higher profile of risk may specifically support the design
of trials (by selecting a sample population more likely to
experience the study outcome, thus reducing the length of the
follow-up) and enhance the intervention efficacy (by excluding
low-risk profile subjects from the study).
Unfortunately, although several algorithms have been
developed over the last decade to support clinicians and
researchers in objectively screening older persons for frailty, a
controversy exists about the optimal instrument to adopt (7).
The major reason for the difficulties in reaching an agreement
probably resides in the multidimensional nature of frailty (1).
Frailty is a syndrome, and its clinical manifestation may greatly
vary. The only way to appropriately measure it is by using
instruments that may comprehensively evaluate the subject’s
overall health status. It is true that most of the available
screening tools share the common concept of a “critical mass”
of symptoms and signs to determine the frailty status (in
accordance to the syndromic nature of the condition).
Nevertheless, each tool tends to identify different sets of frail
subjects depending on its conception and design specificities.
Thus, for example, the Frailty Index proposed by Fried and
colleagues (8) or by Ensrund and colleagues (9) more closely
look at the physical domain of frailty, whereas the measure
designed by Rockwood and colleagues (10) is better focused at
estimating the accumulation of deficits. Moreover, some
instruments have been conceived as screening tools to identify
persons at risk (8, 9, 11), while others are designed to estimate
the clinical reserves of the individual after the completion of
the comprehensive geriatric assessment (10, 12). Another
limitation of these tools is that they are often felt to be more
research-oriented than suitable for the clinical setting. The
physician looks for screening tools able to easily, immediately,
and accurately find support to his/her clinical decisions in the
often crowded and busy environment of a clinic. Long
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The Journal of Frailty & Aging©
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FRAILTY AND AGING
questionnaires, complex scales, or multiple tasks to administer
are (too) easily considered inadapt for the clinical assessment of
the older patient. A possible alternative might be represented by
the adoption of physical performance tests (13), especially
those focused on mobility (a capacity shared by all living
beings, from Drosophila to humans (14)). Physical performance
measures (in particular, gait speed (15, 16)) should not be
anymore considered as mere markers of the physical (or lower
extremity) function. These tests have shown to indeed predict a
wide and heterogeneous spectrum of adverse outcomes, even
those not directly related to the functional domain (e.g.,
hospitalization, institutionalization, mortality). Moreover,
physical performance measures are strongly associated with the
subclinical and clinical factors which are well-established key-
components of frailty (e.g., inflammation (17), oxidative
damage (18, 19), body composition modifications (20),
comorbidities (5, 21), poor lifestyle behaviours (22-24)),
implicitly mimicking the peculiar multidimensionality of the
syndrome (1). Interestingly, for all these reasons, gait speed has
even been proposed as an additional vital sign and a marker of
biological age (15, 25). From this perspective, it might be
suggested frailty as a clinically evident threshold in the
pathophysiological continuum of the aging process.
The adoption of physical performance tests in the screening
of older persons may represent the first step towards a structural
reorganization of the current way to offer health care to older
patients (26). For example, the preliminary evaluation of the 4-
meter gait speed may easily identify subjects presenting the
poorest health status (or frailty) (16), independently of
endogenous and/or exogenous causes. These patients (different
from the “only anagraphically old” ones) should indeed be
those electively forwarded to the geriatrician and in the need of
undergoing the comprehensive geriatric assessment (with
subsequent planification of the individualized intervention)
(15).
Since multiple factors determine and aliment the frailty
syndrome (27), intervening only against one of the alterations
may not be sufficient to restore a solid homeostatic equilibrium
(28). Therefore, it is not surprising that significant results to
reduce the burden of frailty and prevent disability are more
likely to be obtained when adopting interventions acting at
multiple levels (e.g., physical exercise (29), comprehensive
geriatric assessment (30)). Specific research methodologies
have also been developed to adequately study the complexity of
geriatric syndromes (including frailty), such as the standardly-
tailored design of clinical trials (in which participants only
receive the intervention components corresponding to the
presented risk factors) (31-33). In other words, appropriate
modifications to the usual schemes are needed to successfully
study and target frailty.
4
Today, a growing interest is directed towards the study of
age-related conditions, and frailty represents an ideal
benchmark to start. We are at the very beginning of the study of
this syndrome, but our knowledge is exponentially growing.
After all, we need to take into account that the paper by Fried
and colleagues proposing the most commonly used phenotypic
description of the syndrome is only dated 11 years (8). At the
same time, the relative novelty of the topic imposes a cautious
approach and flexibility. Too rigid statements and positions at
the present time may hamper the proper collection of
experience precluding the development of clear definitions and
guidelines.
The frailty syndrome is an extremely exciting, innovative,
and ambitious topic of research with crucial relevance for
medicine of tomorrow (necessarily focused on older persons as
suggested by the epidemiological trends). It is time to start
openly thinking at frailty as a true clinical entity rooted in the
complex scenario of the aging process. Thus, in the attempt to
promote and convey research in this increasingly important
field, the International Association of Gerontology and
Geriatrics and the Global Ageing Research Network recently
decided to develop the present new editorial initiative.
The Journal of Frailty & Aging (or JFA) is born to be a peer-
reviewed international journal aimed at presenting scientific
articles in the area of aging and age-related (sub)clinical
conditions. In particular, it publishes high-quality papers
describing and discussing social, biological, and clinical
features underlying the onset and development of frailty in
older persons. The journal is initially composed of five different
sections entitled 1) “Biology of frailty and aging” (presenting
preclinical studies and experiences focused at identifying,
describing, and understanding the subclinical
pathophysiological mechanisms at the basis of frailty and
aging), 2) “Physical frailty and age-related body composition
modifications” (exploring the physical and functional
components of frailty with special attention to sarcopenia and
obesity), 3) “Neurosciences of frailty and aging” (containing
reports on cognitive and neurological aspects of frailty and age-
related conditions), 4) “Frailty and aging in clinics and public
health” (including the description of multidisciplinary
experiences facing frailty and aging, e.g., onco-geriatrics,
ortho-geriatrics, geriatric cardiology,…), and 5) “Clinical trials
and therapeutics” (reporting findings from pharmacological and
non-pharmacological interventions aimed at preventing,
delaying, or treating frailty and age-related conditions).
In this first article of the Journal of Frailty & Aging, it is
impossible to not warmly thank the Executive Committee of the
International Association of Gerontology and Geriatrics for
trusting and appointing me as Editor-in-Chief. I am honoured
with their choice and committed at doing my best to fully meet
their expectations. Special thanks also go to all the Associate
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The Journal of Frailty & Aging©
Volume 1, Number 1, 2012
THE JOURNAL OF FRAILTY & AGING
Editors and Editorial Board Members for their availability in
accepting to pursue together this new adventure. I indeed
believe the Journal of Frailty & Aging has a distinguished
panel of high-profile investigators, notable coming from
different backgrounds, professional experiences, and Countries.
Finally, I would like to thank the Authors that made this first
issue possible by submitting their manuscripts to this new
journal. I believe the quality of the contributions is very high.
This first issue contains two conceptual papers potentially
stimulating interesting debates on the frailty condition. In a first
paper, Rockwood and Mitnitski (34) discuss the above-
mentioned definition of frailty based on the mathematical
accumulation of clinical deficits (10). At the same time, in a
second article, Gutierrez-Robledo and Avila-Funes (35)
propose an interesting opening towards a needed and more
careful evaluation of social factors as major determinants of
frailty onset. Both these contributions summarize two
presentations given at a recent workshop organized by the
International Association of Gerontology and Geriatrics, the
World Health Organization, and the Société Française de
Gériatrie et Gérontologie. The meeting was held in Athens
(Greece) on January 19-20, 2012 and convened worldwide
experts to discuss on “Promoting access to innovation and
clinical research for frail old persons”. A consensus paper from
the workshop will be shortly published on Journal of Nutrition,
Health and Aging.
This first issue of the Journal of Frailty & Aging contains
interesting original and methodological articles as well. Waters
and colleagues (36) explore the gender-specific differences of
body composition potentially at the basis of the frailty
phenotype. An Italian group of researchers describes the
design, methods, and preliminary results of a large cohort of
older persons aimed at exploring the underlying mechanisms
responsible for dementia (37). Moreover, a valuable
contribution confirms the importance of physical performance
(in particular, muscle strength) in the assessment of older
persons, encouraging its use in the acute care setting (38). Last
but not least, Yamada and colleagues (39) present the
promising results of a clinical trial demonstrating the beneficial
effects of an extremely simple intervention on physical
function in sedentary older persons.
We all hope the journal will soon become a primary resource
of information for both clinicians and researchers daily facing
the complexity of the frailty and aging phenomena. With such
ambitious aim in mind, we invite all the readers to consider
Journal of Frailty & Aging as a potential journal to host their
scientific works. Hopefully, we might contribute together in
fighting age-related conditions (in particular, disability), offer
better services to older persons, and improve quality of life at
advanced age.
5
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