Sage Journals: Discover world-class research

Abstract

The objectives of this literature review were to (1) synthesize biological processes linked to frailty and their corresponding biomarkers and (2) identify potential associations among these processes and biomarkers. In September 2016, PubMed, Cumulative Index to Nursing and Allied Health, Cochrane Library, and Embase were searched. Studies examining biological processes related to frailty in older adults (≥60 years) were included. Studies were excluded if they did not employ specific measures of frailty, did not report the association between biomarkers and frailty, or focused on nonelderly samples (average age < 60). Review articles, commentaries, editorials, and non-English articles were also excluded. Fifty-two articles were reviewed, reporting six biological processes related to frailty and multiple associated biomarkers. The processes (biomarkers) include brain changes (neurotrophic factor, gray matter volume), endocrine dysregulation (growth hormones [insulin-like growth factor-1 and binding proteins], hormones related to glucose and insulin, the vitamin D axis, thyroid function, reproductive axis, and hypothalamic–pituitary–adrenal axis), enhanced inflammation (C-reactive protein, interleukin-6), immune dysfunction (neutrophils, monocytes, neopterin, CD8⁺CD28⁻T cells, albumin), metabolic imbalance (micronutrients, metabolites, enzyme-activity indices, metabolic end products), and oxidative stress (antioxidants, telomere length, glutathione/oxidized glutathione ratio). Bidirectional interrelationships exist within and between these processes. Biomarkers were associated with frailty in varied strengths, and the causality remains unclear. In conclusion, frailty is related to multisystem physiological changes. Future research should examine the dynamic interactions among these processes to inform causality of frailty. Given the multifactorial nature of frailty, a composite index of multisystem biomarkers would likely be more informative than single biomarkers in early detection of frailty.

Keywords

frailty frail elderly older adults biomarkers biological phenomena

Get full access to this article

View all access options for this article.

References

Addison

Drummond

M. J.

LaStayo

P. C.

Dibble

L. E.

Wende

A. R.

McClain

D. A.

Marcus

R. L.

(2014). Intramuscular fat and inflammation differ in older adults: The impact of frailty and inactivity. Journal of Nutrition Health and Aging, 18, 532–538. doi:10.1007/s12603-014-0019-1

Arts

M. H.

Collard

R. M.

Comijs

H. C.

Naude

P. J.

Risselada

Naarding

… Voshaar

R. C.

(2015). Relationship between physical frailty and low-grade inflammation in late-life depression. Journal of American Geriatric Society, 63, 1652–1657. doi:10.1111/jgs.13528

Ashar

F. N.

Moes

Moore

A. Z.

Grove

M. L.

Chaves

P. H. M.

Coresh

… Arking

D. E.

(2015). Association of mitochondrial DNA levels with frailty and all-cause mortality. Journal of Molecular Medicine, 93, 177–186. doi:10.1007/s00109-014-1233-3

Balducci

Extermann

(2000). Management of cancer in the older person: A practical approach. Oncologist, 5, 224–237. doi:10.1634/theoncologist.5-3-224

Bandeen-Roche

Seplaki

C. L.

Huang

Buta

Kalyani

R. R.

Varadhan

… Kasper

J. D.

(2015). Frailty in older adults: A nationally representative profile in the United States. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 70, 1427–1434.

Barzilay

J. I.

Blaum

Moore

Xue

Q. L.

Hirsch

C. H.

Walston

J. D.

Fried

L. P.

(2007). Insulin resistance and inflammation as precursors of frailty: The Cardiovascular Health Study. Archives of Internal Medicine, 167, 635–641. doi:10.1001/archinte.167.7.635

Baylis

Bartlett

D. B.

Syddall

H. E.

Ntani

Gale

C. R.

Cooper

… Sayer

A. A.

(2013). Immune-endocrine biomarkers as predictors of frailty and mortality: A 10-year longitudinal study in community-dwelling older people. Age, 35, 963–971. doi:10.1007/s11357-012-9396-8

Beben

J. H.

Shlipak

M. G.

Sarnak

M. J.

Fried

L. F.

Hoofnagle

A. N.

… Rifkin

D. E.

(2016). Fibroblast growth factor-23 and frailty in elderly community-dwelling individuals: The cardiovascular health study. Journal of American Geriatrics Society, 64, 270–276. doi:10.1111/jgs.13951

Bishop

N. A.

Yankner

B. A.

(2010). Neural mechanisms of ageing and cognitive decline. Nature, 464, 529–535. doi:10.1038/nature08983

10.

Ble

Cherubini

Volpato

Bartali

Walston

J. D.

Windham

B. G.

… Ferrucci

(2006). Lower plasma vitamin E levels are associated with the frailty syndrome: The InCHIANTI study. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 61, 278–283.

11.

Brouwers

Dalmasso

Hatse

Laenen

Kenis

Swerts

… Wildiers

(2015). Biological ageing and frailty markers in breast cancer patients. Aging, 7, 319–333.

12.

Buchman

A. S.

Wilson

R. S.

Boyle

P. A.

Schneider

J. A.

Bennett

D. A.

(2014). Brain pathology contributes to simultaneous change in physical frailty and cognition in old age. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69, 1536–1544. doi:10.1093/gerona/glu117

13.

Buchman

A. S.

Wilson

R. S.

Schneider

J. A.

Bennett

D. A.

(2013). Association of brain pathology with the progression of frailty in older adults. Neurology, 80, 2055–2061. doi:10.1212/WNL.0b013e318294b462

14.

Buta

B. J.

Walston

J. D.

Godino

J. G.

Park

Kalyani

R. R.

Xue

Q. L.

… Varadhan

(2016). Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments. Ageing Research Reviews, 26, 53–61. doi:10.1016/j.arr.2015.12.003

15.

Calvani

Marini

Cesari

Tosato

Anker

S. D.

von Haehling

… Marzetti

(2015). Biomarkers for physical frailty and sarcopenia: State of the science and future developments. Journal of Cachexia, Sarcopenia, and Muscle, 6, 278–286. doi:10.1002/jcsm.12051

16.

Ceci

Duranti

Rossi

Savini

Sabatini

(2011). Skeletal muscle differentiation: Role of dehydroepiandrosterone sulfate. Hormone and Metabolic Research, 43, 702–707.

17.

Cesari

Penninx

B. W.

Pahor

Lauretani

Corsi

A. M.

Williams

G. R.

… Ferrucci

(2004). Inflammatory markers and physical performance in older persons: The InCHIANTI study. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59, M242–M248.

18.

Chen

Jiang

Zhang

MacKenzie

K. R.

Stossi

Palzkill

… Wang

(2017). Reversible reaction-based fluorescent probe for real-time imaging of glutathione dynamics in mitochondria. ACS Sensors, 2, 1257–1261.

19.

Chen

W. T.

Chou

K. H.

Liu

L. K.

Lee

P. L.

Lee

W. J.

Chen

L. K.

… Lin

C. P.

(2015). Reduced cerebellar gray matter is a neural signature of physical frailty. Human Brain Mapping, 36, 3666–3676. doi:10.1002/hbm.22870

20.

Cheng

Hou

Mattson

M. P.

(2010). Mitochondria and neuroplasticity. ASN Neuro, 2, e00045. doi:10.1042/an20100019

21.

Choi

Ahn

Kim

Won

C. W.

(2015). Global prevalence of physical frailty by Fried’s criteria in community-dwelling elderly with national population-based surveys. Journal of the American Medical Directors Association, 16, 548–550. doi:10.1016/j.jamda.2015.02.004

22.

Clegg

Young

Iliffe

Rikkert

M. O.

Rockwood

(2013). Frailty in elderly people. Lancet, 381, 752–762. doi:10.1016/S0140-6736(12)62167-9

23.

Clejan

Collipp

P. J.

Maddaiah

V. T.

(1980). Hormones and liver mitochondria: Influence of growth hormone, thyroxine, testosterone, and insulin on thermotropic effects of respiration and fatty acid composition of membranes. Archives of Biochemistry and Biophysics, 203, 744–752. doi:10.1016/0003-9861(80)90234-9.

24.

Coelho

F. M.

Pereira

D. S.

Lustosa

L. P.

Silva

J. P.

Dias

J. M. D.

Dias

R. C. D.

… Pereira

L. S. M.

(2012). Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women. Archives of Gerontology and Geriatrics, 54, 415–420. doi:10.1016/j.archger.2011.05.014

25.

Colburn

DeGruttola

DeMets

Downing

Hoth

Oates

,…Biomarkers Definitions Working Group. (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. . Clinical Pharmacology & Therapeutics, 69, 89–95.

26.

Collard

R. M.

Boter

Schoevers

R. A.

Oude Voshaar

R. C.

(2012). Prevalence of frailty in community-dwelling older persons: A systematic review. Journal of the American Geriatrics Society, 60, 1487–1492. doi:10.1111/j.1532-5415.2012.04054.x

27.

Collerton

Martin-Ruiz

Davies

Hilkens

C. M.

Isaacs

Kolenda

… Kirkwood

T. B. L.

(2012). Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: Cross-sectional findings from the Newcastle 85+ study. Mechanisms of Ageing and Development, 133, 456–466. doi:10.1016/j.mad.2012.05.005

28.

Cooper

Dere

Evans

Kanis

J. A.

Rizzoli

Sayer

A. A.

… Reginster

J. Y.

(2012). Frailty and sarcopenia: Definitions and outcome parameters. Osteoporosis International, 23, 1839–1848. doi:10.1007/s00198-012-1913-1

29.

Corona

Polesel

Fratino

Miolo

Rizzolio

Crivellari

… Toffoli

(2014). Metabolomics biomarkers of frailty in elderly breast cancer patients. Journal of Cellular Physiology, 229, 898–902. doi:10.1002/jcp.24520

30.

Corwin

E. J.

Ferranti

(2016). Integration of biomarkers to advance precision nursing interventions for family research across the lifespan. Nursing Outlook, 64, 292–298. doi:10.1021/acssensors.7b00425

31.

Cushman

Psaty

B. M.

Macy

Bovill

E. G.

Cornell

E. S.

Kuller

L. H.

Tracy

R. P.

(1996). Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 16, 1163–1169.

32.

Dalrymple

L. S.

Katz

Rifkin

D. E.

Siscovick

Newman

A. B.

Fried

L. F.

… Shlipak

M. G.

(2013). Kidney function and prevalent and incident frailty. Clinical Journal of the American Society of Nephrology, 8, 2091–2099. doi:10.2215/cjn.02870313

33.

Davalos

Akassoglou

(2012). Fibrinogen as a key regulator of inflammation in disease. Seminars in Immunopathology, 34, 43–62. doi:10.1007/s00281-011-0290-8

34.

Distefano

Standley

R. A.

Zhang

Carnero

E. A.

Cornnell

H. H.

Coen

P. M.

(2017). Physical activity unveils the relationship between mitochondrial energetics, muscle quality and physical function in older adults. bioRxiv, 164160. doi.org/10.1101/164160.

35.

Ehlenbach

W. J.

Larson

E. B.

Randall Curtis

Hough

C. L.

(2015). Physical function and disability after acute care and critical illness hospitalizations in a prospective cohort of older adults. Journal of the American Geriatrics Society, 63, 2061–2069.

36.

El Assar

Angulo

Carnicero

J. A.

Walter

Garcia-Garcia

F. J.

Lopez-Hernandez

… Rodriguez-Manas

(2017). Frailty is associated with lower expression of genes involved in cellular response to stress: Results from the Toledo Study for Healthy Aging. Journal of the American Medical Directors Association, 18, 734.e731–734.e737. doi:10.1016/j.jamda.2017.04.019

37.

Ensrud

K. E.

Blackwell

T. L.

Cauley

J. A.

Cummings

S. R.

Barrett-Connor

Dam

T. T.

… Cawthon

P. M.

(2011). Circulating 25-hydroxyvitamin D levels and frailty in older men: The osteoporotic fractures in men study. Journal of the American Geriatrics Society, 59, 101–106. doi:10.1111/j.1532-5415.2010.03201.x

38.

Ensrud

K. E.

Ewing

S. K.

Taylor

B. C.

Fink

H. A.

Stone

K. L.

Cauley

J. A.

… Cawthon

P. M.

(2007). Frailty and risk of falls, fracture, and mortality in older women: The study of osteoporotic fractures. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62, 744–751.

39.

Espinoza

S. E.

Jung

Hazuda

(2012). Frailty transitions in the San Antonio longitudinal study of aging. Journal of American Geriatric Society, 60, 652–660. doi:10.1111/j.1532-5415.2011.03882.x

40.

Fedarko

N. S.

(2011). The biology of aging and frailty. Clinics in Geriatric Medicine, 27, 27–37. doi:10.1016/j.cger.2010.08.006

41.

Fougere

Vellas

Van Kan

G. A.

Cesari

(2015). Identification of biological markers for better characterization of older subjects with physical frailty and sarcopenia. Translational Neuroscience, 6, 103–110. doi:10.1515/tnsci-2015-0009

42.

Fried

L. P.

Ferrucci

Darer

Williamson

J. D.

Anderson

(2004). Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59, M255–M263.

43.

Fried

L. P.

Tangen

C. M.

Walston

Newman

A. B.

Hirsch

Gottdiener

,…Cardiovascular Health Study Collaborative Research Group. (2001). Frailty in older adults evidence for a phenotype. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 56, M146–M157.

44.

Gale

C. R.

Baylis

Cooper

Sayer

A. A.

(2013). Inflammatory markers and incident frailty in men and women: The English Longitudinal Study of Ageing. Age, 35, 2493–2501. doi:10.1007/s11357-013-9528-9

45.

Gilson

Londoño-Vallejo

J. A.

(2007). Telomere length profiles in humans: All ends are not equal. Cell Cycle, 6, 2486–2494. doi:10.4161/cc.6.20.4798

46.

Gogvadze

Orrenius

Zhivotovsky

(2008). Mitochondria in cancer cells: What is so special about them? Trends in Cell Biology, 18, 165–173.

47.

Gruenewald

T. L.

Seeman

T. E.

Karlamangla

A. S.

Sarkisian

C. A.

(2009). Allostatic load and frailty in older adults. Journal of American Geriatrics Society, 57, 1525–1531. doi:10.1111/j.1532-5415.2009.02389.x

48.

Harman

(1956). Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology, 11, 298–300.

49.

Hart

Paudel

M. L.

Taylor

B. C.

Ishani

Orwoll

E. S.

Cawthon

P. M.

Ensrud

K. E.

(2013). Cystatin C and frailty in older men. Journal of American Geriatrics Society, 61, 1530–1536. doi:10.1111/jgs.12413

50.

Howard

Ferrucci

Sun

Fried

L. P.

Walston

Varadhan

… Semba

R. D.

(2007). Oxidative protein damage is associated with poor grip strength among older women living in the community. Journal of Applied Physiology, 103, 17–20.

51.

Hubbard

R. E.

O’Mahony

M. S.

Calver

B. L.

Woodhouse

K. W.

(2008). Plasma esterases and inflammation in ageing and frailty. European Journal of Clinical Pharmacology, 64, 895–900. doi:10.1007/s00228-008-0499-1

52.

Hubbard

R. E.

O’Mahony

M. S.

Savva

G. M.

Calver

B. L.

Woodhouse

K. W.

(2009). Inflammation and frailty measures in older people. Journal of Cellular and Molecular Medicine, 13, 3103–3109. doi:10.1111/j.1582-4934.2009.00733.x

53.

Hubbard

R. E.

Woodhouse

K. W.

(2010). Frailty, inflammation and the elderly. Biogerontology, 11, 635–641. doi:10.1007/s10522-010-9292-5

54.

Hunt

K. J.

Walsh

B. M.

Voegeli

Roberts

H. C.

(2010). Inflammation in aging part 1: Physiology and immunological mechanisms. Biological Research for Nursing, 11, 245–252.

55.

Hyde

Flicker

Almeida

O. P.

Hankey

G. J.

McCaul

K. A.

Chubb

S. A.

Yeap

B. B.

(2010). Low free testosterone predicts frailty in older men: The health in men study. Journal of Clinical Endocrinology & Metabolism, 95, 3165–3172. doi:10.1210/jc.2009-2754

56.

Inglés

Gambini

Carnicero

J. A.

García-García

F. J.

Rodríguez-Mañas

Olaso-González

… Viña

(2014). Oxidative stress is related to frailty, not to age or sex, in a geriatric population: Lipid and protein oxidation as biomarkers of frailty. Journal of the American Geriatrics Society, 62, 1324–1328.

57.

Inglés

Gambini

Mas-Bargues

García-García

F. J.

Viña

Borrás

(2017). Brain-derived neurotrophic factor as a marker of cognitive frailty. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 72, 450–451. doi:10.1093/gerona/glw145

58.

Johansen

K. L.

Dalrymple

L. S.

Delgado

Chertow

G. M.

Segal

M. R.

Chiang

… Kaysen

G. A.

(2017). Factors associated with frailty and its trajectory among patients on hemodialysis. Clinical Journal of the American Society of Nephrology, 12, 1100–1108. doi:10.2215/cjn.12131116

59.

Joseph

Pandit

Zangbar

Kulvatunyou

Hasmi

Green

… Rhee

(2014). Superiority of frailty over age in predicting outcomes among geriatric trauma patients: A prospective analysis. JAMA Surgery, 149, 766–772. doi:10.1001/jamasurg.2014.296

60.

Kahlon

Pederson

Majumdar

S. R.

Belga

Lau

Fradette

… Padwal

R. S.

(2015). Association between frailty and 30-day outcomes after discharge from hospital. Canadian Medical Association Journal, 187, 799–804. doi:10.1503/cmaj.150100

61.

Kalyani

R. R.

Tian

Xue

Q. L.

Walston

Cappola

A. R.

Fried

L. P.

… Blaum

C. S.

(2012). Hyperglycemia and incidence of frailty and lower extremity mobility limitations in older women. Journal of American Geriatrics Society, 60, 1701–1707. doi:10.1111/j.1532-5415.2012.04099.x

62.

Kalyani

R. R.

Varadhan

Weiss

C. O.

Fried

L. P.

Cappola

A. R.

(2012a). Frailty status and altered glucose-insulin dynamics. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 67, 1300–1306. doi:10.1093/gerona/glr141

63.

Kalyani

R. R.

Varadhan

Weiss

C. O.

Fried

L. P.

Cappola

A. R.

(2012b). Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women. Journal of Nutrition Health and Aging, 16, 679–686. doi:10.1007/s12603-012-0369-5

64.

Lai

H. Y.

Chang

H. T.

Lee

Y. L.

Hwang

S. J.

(2014). Association between inflammatory markers and frailty in institutionalized older men. Maturitas, 79, 329–333. doi:10.1016/j.maturitas.2014.07.014

65.

Leng

S. X.

Cappola

A. R.

Andersen

R. E.

Blackman

M. R.

Koenig

Blair

Walston

J. D.

(2004). Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clinical and Experimental Research, 16, 153–157. doi:10.1007/bf03324545

66.

Leng

S. X.

Hung

Cappola

A. R.

Xue

Q. L.

Fried

L. P.

(2009). White blood cell counts, insulin-like growth factor-1 levels, and frailty in community-dwelling older women. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 64, 499–502. doi:10.1093/gerona/gln047

67.

Leng

S. X.

Tian

Matteini

Hughes

Jain

… Fedarko

N. S.

(2011). IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age and Ageing, 40, 475–481. doi:10.1093/ageing/afr047

68.

Leng

S. X.

Xue

Q. L.

Tian

Huang

Yeh

S. H.

Fried

L. P.

(2009). Associations of neutrophil and monocyte counts with frailty in community-dwelling disabled older women: Results from the Women’s Health and Aging Studies I. Experimental Gerontology, 44, 511–516. doi:10.1016/j.exger.2009.05.005

69.

Leng

S. X.

Xue

Q. L.

Tian

Walston

J. D.

Fried

L. P.

(2007). Inflammation and frailty in older women. Journal of the American Geriatrics Society, 55, 864–871.

70.

Lindsay

R. M.

(1994). Neurotrophic growth factors and neurodegenerative diseases: Therapeutic potential of the neurotrophins and ciliary neurotrophic factor. Neurobiology of Aging, 15, 249–251.

71.

Liu

C. K.

Lyass

Larson

M. G.

Massaro

J. M.

Wang

D’Agostino

R. B.

Sr … Murabito

J. M.

(2016). Biomarkers of oxidative stress are associated with frailty: The Framingham Offspring Study. Age, 38, 1. doi:10.1007/s11357-015-9864-z

72.

Margetic

(2012). Inflammation and haemostasis. Biochemia Medica, 22, 49–62.

73.

Mather

Jacobsen

L. A.

Pollard

K. M.

(2015). Aging in the United States. Population Bulletin, 70. Retrieved from http://www.prb.org/pdf16/aging-us-population-bulletin.pdf

74.

Matteini

A. M.

Walston

J. D.

Fallin

M. D.

Bandeen-Roche

Kao

W. H.

Semba

R. D.

… Stabler

S. P.

(2008). Markers of B-vitamin deficiency and frailty in older women. Journal of Nutrition, Health, & Aging, 12, 303–308.

75.

Maxwell

C. A.

Wang

(2017). Understanding frailty: A nurse’s guide. Nursing Clinics of North America, 52, 349–361. doi:10.1016/j.cnur.2017.04.003

76.

McCarty

M. F.

(2005). Secondary hyperparathyroidism promotes the acute phase response—a rationale for supplemental vitamin D in prevention of vascular events in the elderly. Medical Hypotheses, 64, 1022–1026.

77.

Mekli

Marshall

Vanhoutte

Tampubolon

Nazroo

Pendleton

(2017). The genetics of frailty: Summary of the results of the genetics work in the frail project. Innovation in Aging, 1, 137–137. doi:10.1093/geroni/igx004.552

78.

Mercer

S. W.

Smith

S. M.

Wyke

O’Dowd

Watt

G. C.

(2009). Multimorbidity in primary care: Developing the research agenda. Family Practice, 26, 79–80. doi:10.1093/fampra/cmp020

79.

Metzelthin

S. F.

Daniëls

van Rossum

Cox

Habets

de Witte

L. P.

Kempen

G. I. J. M.

(2012). A nurse-led interdisciplinary primary care approach to prevent disability among community-dwelling frail older people: A large-scale process evaluation. International Journal of Nursing Studies, 50, 1184–1196. doi:10.1016/j.ijnurstu.2012.12.016

80.

Miller

D. B.

O’Callaghan

J. P.

(2005). Aging, stress and the hippocampus. Ageing Research Reviews, 4, 123–140. doi:10.1016/j.arr.2005.03.002***

81.

Miller

R. A.

(1996). The aging immune system: Primer and prospectus. Science, 273, 70.

82.

Mills

E. L.

Kelly

O’Neill

L. A. J.

(2017). Mitochondria are the powerhouses of immunity. Nature Immunology, 18, 488–498. doi:10.1038/ni.3704

83.

Mitnitski

Collerton

Martin-Ruiz

Jagger

von Zglinicki

Rockwood

Kirkwood

T. B.

(2015). Age-related frailty and its association with biological markers of ageing. BMC Medicine, 13, 161. doi:10.1186/s12916-015-0400-x

84.

Moher

Liberati

Tetzlaff

Altman

D. G

(2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Journal of Clinical Epidemiology, 62, 1606–1612. doi:10.1016/j.jclinepi.2009.06.005

85.

Mohler

M. J.

Fain

M. J.

Wertheimer

A. M.

Najafi

Nikolich-Žugich

(2014). The frailty syndrome: Clinical measurements and basic underpinnings in humans and animals. Experimental Gerontology, 54, 6–13. doi:10.1016/j.exger.2014.01.024

86.

Morley

J. E.

Malmstrom

Miller

(2012). A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. Journal of Nutrition, Health & Aging, 16, 601–608.

87.

Namioka

Hanyu

Hirose

Hatanaka

Sato

Shimizu

(2016). Oxidative stress and inflammation are associated with physical frailty in patients with Alzheimer’s disease. Geriatrics & Gerontology International, 17, 913–918. doi:10.1111/ggi.12804

88.

Nicholson

Meyer

Flatley

Holman

(2013). The experience of living at home with frailty in old age: A psychosocial qualitative study. International Journal of Nursing Studies, 50, 1172–1179. doi:10.1016/j.ijnurstu.2012.01.006

89.

Noble

E. E.

Billington

C. J.

Kotz

C. M.

Wang

(2011). The lighter side of BDNF. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology, 300, R1053–R1069.

90.

Orlovsky

Dosenko

Spiga

Skibo

Lightman

(2014). Hippocampus remodeling by chronic stress accompanied by GR, proteasome and caspase-3 overexpression. Brain Research, 1593, 83–94.

91.

Percheron

Hogrel

J. Y.

Denot-Ledunois

Fayet

Forette

Baulieu

E. E.

… Marini

J. F.

(2003). Effect of 1-year oral administration of dehydroepiandrosterone to 60- to 80-year-old individuals on muscle function and cross-sectional area: A double-blind placebo-controlled trial. Archives of Internal Medicine, 163, 720–727.

92.

Picard

McManus

M. J.

Gray

J. D.

Nasca

Moffat

Kopinski

P. K.

… Wallace

D. C.

(2015). Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress. Proceedings of the National Academy of Sciences of the United States of America, 112, E6614–6623. doi:10.1073/pnas.1515733112

93.

Puts

M. T.

Visser

Twisk

J. W.

Deeg

D. J.

Lips

(2005). Endocrine and inflammatory markers as predictors of frailty. Clinical Endocrinology, 63, 403–411.

94.

Raefsky

S. M.

Mattson

M. P.

(2017). Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance. Free Radical Biology & Medicine, 102, 203–216. doi:10.1016/j.freeradbiomed.2016.11.045

95.

Reiner

A. P.

Aragaki

A. K.

Gray

S. L.

Wactawski-Wende

Cauley

J. A.

Cochrane

B. B.

… LaCroix

A. Z.

(2009). Inflammation and thrombosis biomarkers and incident frailty in postmenopausal women. American Journal of Medicine, 122, 947–954. doi:10.1016/j.amjmed.2009.04.016

96.

Robertson

D. A.

Savva

G. M.

Kenny

R. A.

(2013). Frailty and cognitive impairment—A review of the evidence and causal mechanisms. Ageing Research Reviews, 12, 840–851. doi:10.1016/j.arr.2013.06.004

97.

Robson

Shephard

Kirsch

(1994). Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1β, IL-6 and plasminogen activator inhibitors from monocytes in vitro. British Journal of Haematology, 86, 322–326.

98.

Rockwood

Mitnitski

(2007). Frailty in relation to the accumulation of deficits. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62, 722–727.

99.

Rockwood

Song

MacKnight

Bergman

Hogan

D. B.

McDowell

Mitnitski

(2005). A global clinical measure of fitness and frailty in elderly people. Canadian Medical Association Journal, 173, 489–495. doi:10.1503/cmaj.050051

100.

Rohleder

Kudielka

B. M.

Hellhammer

D. H.

Wolf

J. M.

Kirschbaum

(2002). Age and sex steroid-related changes in glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress. Journal of Neuroimmunology, 126, 69–77.

101.

Ronning

Wyller

T. B.

Seljeflot

Jordhoy

M. S.

Skovlund

Nesbakken

Kristjansson

S. R.

(2010). Frailty measures, inflammatory biomarkers and post-operative complications in older surgical patients. Age and Ageing, 39, 758–761. doi:10.1093/ageing/afq123

102.

Rosca

M. G.

Hoppel

C. L.

(2010). Mitochondria in heart failure. Cardiovascular Research, 88, 40–50.

103.

Rosmond

Björntorp

(2000). The hypothalamic–pituitary–adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. Journal of Internal Medicine, 247, 188–197.

104.

Saliba

Elliott

Rubenstein

L. Z.

Solomon

D. H.

Young

R. T.

Kamberg

C. J.

… Sloss

E. M.

(2001). The Vulnerable Elders Survey: A tool for identifying vulnerable older people in the community. Journal of the American Geriatrics Society, 49, 1691–1699.

105.

Sanchis

Nuñez

Ruiz

Bonanad

Fernandez

Cauli

… Nuñez

(2015). Usefulness of clinical data and biomarkers for the identification of frailty after acute coronary syndromes. Canadian Journal of Cardiology, 31, 1462–1468. doi:10.1016/j.cjca.2015.07.737

106.

Sarkisian

C. A.

Gruenewald

T. L.

John Boscardin

Seeman

T. E.

(2008). Preliminary evidence for subdimensions of geriatric frailty: The MacArthur study of successful aging. Journal of the American Geriatrics Society, 56, 2292–2297.

107.

Schäbitz

W. R.

Steigleder

Cooper-Kuhn

C. M.

Schwab

Sommer

Schneider

Kuhn

H. G.

(2007). Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis. Stroke, 38, 2165–2172.

108.

Schleithoff

S. S.

Zittermann

Tenderich

Berthold

H. K.

Stehle

Koerfer

(2006). Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: A double-blind, randomized, placebo-controlled trial. American Journal of Clinical Nutrition, 83, 754–759.

109.

Seeman

T. E.

Singer

B. H.

Rowe

J. W.

Horwitz

R. I.

McEwen

B. S.

(1997). Price of adaptation—allostatic load and its health consequences: MacArthur studies of successful aging. Archives of Internal Medicine, 157, 2259–2268.

110.

Semba

R. D.

Bartali

Zhou

Blaum

C. W.

Fried

L. P.

(2006). Low serum micronutrient concentrations predict frailty among older women living in the community. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 61, 594–599.

111.

Semba

R. D.

Margolick

J. B.

Leng

Walston

Ricks

M. O.

Fried

L. P.

(2005). T cell subsets and mortality in older community-dwelling women. Experimental Gerontology, 40, 81–87. doi:10.1016/j.exger.2004.09.006

112.

Serviddio

Romano

A. D.

Greco

Rollo

Bellanti

Altomare

Vendemiale

(2009). Frailty syndrome is associated with altered circulating redox balance and increased markers of oxidative stress. International Journal of Immunopathology and Pharmacology, 22, 819–827.

113.

Shamliyan

Talley

K. M.

Ramakrishnan

Kane

R. L.

(2013). Association of frailty with survival: A systematic literature review. Ageing Research Reviews, 12, 719–736.

114.

Sterling

Milch

Brenner

Lazarus

(1977). Thyroid hormone action: The mitochondrial pathway. Science, 197, 996–999. doi:10.1126/science.196334

115.

Szanton

Allen

Seplaki

Bandeen-Roche

Fried

(2009). Allostatic load and frailty in the women’s health and aging studies. Biological Research for Nursing, 10, 248–256.

116.

Tajar

Lee

D. M.

Pye

S. R.

O’Connell

M. D.

Ravindrarajah

Gielen

… O’Neill

T. W.

(2013). The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men. Age and Ageing, 42, 352–359. doi:10.1093/ageing/afs162

117.

Tajar

O’Connell

M. D. L.

Mitnitski

A. B.

O’Neill

T. W.

Searle

S. D.

Huhtaniemi

I. T.

,…the European Male Aging Study, G. (2011). Frailty in relation to variations in hormone levels of the hypothalamic–pituitary–testicular axis in older men: Results from the European male aging study. Journal of the American Geriatrics Society, 59, 814–821. doi:10.1111/j.1532-5415.2011.03398.x

118.

Trevisan

Veronese

Maggi

Baggio

Toffanello

E. D.

Zambon

… Sergi

(2017). Factors influencing transitions between frailty states in elderly adults: The Progetto Veneto Anziani longitudinal study. Journal of American Geriatrics Society, 65, 179–184. doi:10.1111/jgs.14515

119.

Tschopp

(2011). Mitochondria: Sovereign of inflammation? European Journal of Immunology, 41, 1196–1202. doi:10.1002/eji.201141436

120.

Tsigos

Chrousos

G. P.

(2002). Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. Journal of Psychosomatic Research, 53, 865–871.

121.

Urpi-Sarda

Andres-Lacueva

Rabassa

Ruggiero

Zamora-Ros

Bandinelli

… Cherubini

(2015). The relationship between urinary total polyphenols and the frailty phenotype in a community-dwelling older population: The InCHIANTI Study. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 70, 1141–1147. doi:10.1093/gerona/glv026

122.

Varadhan

Chaves

P. H.

Lipsitz

L. A.

Stein

P. K.

Tian

Windham

B. G.

… Fried

L. P.

(2009). Frailty and impaired cardiac autonomic control: New insights from principal components aggregation of traditional heart rate variability indices. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 64, 682–687. doi:10.1093/gerona/glp013

123.

Varadhan

Walston

Cappola

A. R.

Carlson

M. C.

Wand

G. S.

Fried

L. P.

(2008). Higher levels and blunted diurnal variation of cortisol in frail older women. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 63, 190–195.

124.

Visser

Goodpaster

B. H.

Kritchevsky

S. B.

Newman

A. B.

Nevitt

Rubin

S. M.

… Harris

T. B.

(2005). Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 60, 324–333.

125.

Visser

Kritchevsky

S. B.

Goodpaster

B. H.

Newman

A. B.

Nevitt

Stamm

Harris

T. B.

(2002). Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: The health, aging and body composition study. Journal of the American Geriatrics Society, 50, 897–904.

126.

von Elm

Altman

D. G.

Egger

Pocock

S. J.

Gøtzsche

P. C.

Vandenbroucke

J. P.

(2007). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies. Preventive Medicine, 45, 247–251. doi:10.1016/j.ypmed.2007.08.012

127.

Walston

McBurnie

M. A.

Newman

Tracy

R. P.

Kop

W. J.

Hirsch

C. H.

… Fried

L. P.

(2002). Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: Results from the cardiovascular health study. Archives of Internal Medicine, 162, 2333–2341.

128.

Wang

Boehm

Mion

L. C.

(2017). Intrinsic capacity in older hospitalized adults: Implications for nursing practice. Geriatric Nursing, 38, 359–361. doi:10.1016/j.gerinurse.2017.06.008

129.

Westra

B. L.

Clancy

T. R.

Sensmeier

Warren

J. J.

Weaver

Delaney

C. W.

(2015). Nursing knowledge: Big data science—Implications for nurse leaders. Nursing Administration Quarterly, 39, 304–310. doi:10.1097/naq.0000000000000130

130.

Whitson

H. E.

Arnold

A. M.

Yee

L. M.

Mukamal

K. J.

Kizer

J. R.

Djousse

… Zieman

(2014). Serum carboxymethyl-lysine, disability, and frailty in older persons: The cardiovascular health study. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69, 710–716. doi:10.1093/gerona/glt155

131.

Woo

Tang

N. L.

Suen

Leung

J. C.

Leung

P. C.

(2008). Telomeres and frailty. Mechanisms of Ageing and Development, 129, 642–648. doi:10.1016/j.mad.2008.08.003

132.

World Health Organization. (2015). World report on ageing and health. Geneva, Switzerland: Author. Retrieved from http://www.who.int/ageing/events/world-report-2015-launch/en/

133.

I. C.

Shiesh

S. C.

Kuo

P. H.

Lin

X. Z.

(2009). High oxidative stress is correlated with frailty in elderly Chinese. Journal of American Geriatrics Society, 57, 1666–1671. doi:10.1111/j.1532-5415.2009.02392.x

134.

Xue

Q. L.

(2011). The frailty syndrome: Definition and natural history. Clinics in Geriatric Medicine, 27, 1–15. doi:10.1016/j.cger.2010.08.009

135.

Yeap

B. B.

Alfonso

Chubb

S. A.

Walsh

J. P.

Hankey

G. J.

Almeida

O. P.

Flicker

(2012). Higher free thyroxine levels are associated with frailty in older men: The health in men study. Clinical Endocrinology, 76, 741–748. doi:10.1111/j.1365-2265.2011.04290.x

136.

Yeap

B. B.

Paul Chubb

S. A.

Lopez

K. K.

Hankey

G. J.

Flicker

(2013). Associations of insulin-like growth factor-I and its binding proteins and testosterone with frailty in older men. Clinical Endocrinology, 78, 752–759. doi:10.1111/cen.12052

137.

Young

Hughes

Russell

Parker

M. J.

Nichols

P. J. R.

(1980). Measurement of quadriceps muscle wasting by ultrasonography. Rheumatology, 19, 141–148. doi:10.1093/rheumatology/19.3.141

138.

Zaslavsky

Cochrane

B. B.

Thompson

H. J.

Woods

N. F.

Herting

J. R.

LaCroix

(2013). Frailty: A review of the first decade of research. Biological Research for Nursing, 15, 422–432. doi:10.1177/1099800412462866

139.

Zaslavsky

Walker

R. L.

Crane

P. K.

Gray

S. L.

Larson

E. B.

(2016). Glucose levels and risk of frailty. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences, 71, 1223–1229. doi:10.1093/gerona/glw024

140.

Zhu

Liu

Wang

Shi

Xie

… Wang

(2016). C-reactive protein, frailty and overnight hospital admission in elderly individuals: A population-based study. Archives of Gerontology and Geriatrics, 64, 1–5. doi:10.1016/j.archger.2015.08.009

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.92 MB

Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review

Abstract

Keywords

Get full access to this article

References

Supplementary Material