Biomarkers of Aging: From Function to Molecular Biology

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Abstract

Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

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Most cited references 63

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Inflamm-aging. An evolutionary perspective on immunosenescence.

C Franceschi, M BonaFe, S Valensin … (2000)

In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

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The role of mitochondria in aging.

Ana Bratic, Nils-Göran Larsson (2013)

Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysfunction and major phenotypes associated with aging. Somatic mitochondrial DNA (mtDNA) mutations and respiratory chain dysfunction accompany normal aging, but the first direct experimental evidence that increased mtDNA mutation levels contribute to progeroid phenotypes came from the mtDNA mutator mouse. Recent evidence suggests that increases in aging-associated mtDNA mutations are not caused by damage accumulation, but rather are due to clonal expansion of mtDNA replication errors that occur during development. Here we discuss the caveats of the traditional mitochondrial free radical theory of aging and highlight other possible mechanisms, including insulin/IGF-1 signaling (IIS) and the target of rapamycin pathways, that underlie the central role of mitochondria in the aging process.

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Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability.

Ian Janssen, Robert Ross, Steven B Heymsfield (2002)

To establish the prevalence of sarcopenia in older Americans and to test the hypothesis that sarcopenia is related to functional impairment and physical disability in older persons. Cross-sectional survey. Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III). Fourteen thousand eight hundred eighteen adult NHANES III participants aged 18 and older. The presence of sarcopenia and the relationship between sarcopenia and functional impairment and disability were examined in 4,504 adults aged 60 and older. Skeletal muscle mass was estimated from bioimpedance analysis measurements and expressed as skeletal muscle mass index (SMI = skeletal muscle mass/body mass x 100). Subjects were considered to have a normal SMI if their SMI was greater than -one standard deviation above the sex-specific mean for young adults (aged 18-39). Class I sarcopenia was considered present in subjects whose SMI was within -one to -two standard deviations of young adult values, and class II sarcopenia was present in subjects whose SMI was below -two standard deviations of young adult values. The prevalence of class I and class II sarcopenia increased from the third to sixth decades but remained relatively constant thereafter. The prevalence of class I (59% vs 45%) and class II (10% vs 7%) sarcopenia was greater in the older (> or = 60 years) women than in the older men (P <.001). The likelihood of functional impairment and disability was approximately two times greater in the older men and three times greater in the older women with class II sarcopenia than in the older men and women with a normal SMI, respectively. Some of the associations between class II sarcopenia and functional impairment remained significant after adjustment for age, race, body mass index, health behaviors, and comorbidity. Reduced relative skeletal muscle mass in older Americans is a common occurrence that is significantly and independently associated with functional impairment and disability, particularly in older women. These observations provide strong support for the prevailing view that sarcopenia may be an important and potentially reversible cause of morbidity and mortality in older persons.

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Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 02 June 2016

Publication date Collection: June 2016

Volume: 8

Issue: 6

Electronic Location Identifier: 338

Affiliations

[1 ]Research Platform Active Ageing, University of Vienna, Althanstrasse 14, Vienna 1090, Austria; barbara.wessner@ 123456univie.ac.at (B.W.); bernhard.franzke@ 123456univie.ac.at (B.F.)

[2 ]Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna 1090, Austria

[3 ]Liggins Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; d.cameron-smith@ 123456auckland.ac.nz

[4 ]Department of Sport and Exercise Physiology, Centre for Sport Science and University Sports, University of Vienna, Auf der Schmelz 6, Vienna 1150, Austria

Author notes

[* ]Correspondence: karl-heinz.wagner@ 123456univie.ac.at ; Tel.: +43-1-4277-54930

Article

Publisher ID: nutrients-08-00338

DOI: 10.3390/nu8060338

PMC ID: 4924179

PubMed ID: 27271660

SO-VID: 273765b6-5dd9-4c51-88dd-381497b7b587

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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Biomarkers of Aging: From Function to Molecular Biology

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Abstract

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Aging Pathobiology and Therapeutics

Most cited references 63

Inflamm-aging. An evolutionary perspective on immunosenescence.

The role of mitochondria in aging.

Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability.

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