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Mutat Res Rev Mutat Res. 2015 Oct-Dec;766:48-57. doi: 10.1016/j.mrrev.2015.08.001. Epub 2015 Aug 28.

Super DNAging-New insights into DNA integrity, genome stability and telomeres in the oldest old.

Author information

1
University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria.
2
University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria; Queensland University of Technology, Faculty of Health, School of Biomedical Sciences, Institute of Health and Biomedical Innovation (IHBI), Tissue Repair and Regeneration Group, 60 Musk Avenue, Kelvin Grove Campus, Brisbane, QLD 4059, Australia.
3
University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria; University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraße 14, 1090 Vienna, Austria. Electronic address: karl-heinz.wagner@univie.ac.at.

Abstract

Reductions in DNA integrity, genome stability, and telomere length are strongly associated with the aging process, age-related diseases as well as the age-related loss of muscle mass. However, in people reaching an age far beyond their statistical life expectancy the prevalence of diseases, such as cancer, cardiovascular disease, diabetes or dementia, is much lower compared to "averagely" aged humans. These inverse observations in nonagenarians (90-99 years), centenarians (100-109 years) and super-centenarians (110 years and older) require a closer look into dynamics underlying DNA damage within the oldest old of our society. Available data indicate improved DNA repair and antioxidant defense mechanisms in "super old" humans, which are comparable with much younger cohorts. Partly as a result of these enhanced endogenous repair and protective mechanisms, the oldest old humans appear to cope better with risk factors for DNA damage over their lifetime compared to subjects whose lifespan coincides with the statistical life expectancy. This model is supported by study results demonstrating superior chromosomal stability, telomere dynamics and DNA integrity in "successful agers". There is also compelling evidence suggesting that life-style related factors including regular physical activity, a well-balanced diet and minimized psycho-social stress can reduce DNA damage and improve chromosomal stability. The most conclusive picture that emerges from reviewing the literature is that reaching "super old" age appears to be primarily determined by hereditary/genetic factors, while a healthy lifestyle additionally contributes to achieving the individual maximum lifespan in humans. More research is required in this rapidly growing population of super old people. In particular, there is need for more comprehensive investigations including short- and long-term lifestyle interventions as well as investigations focusing on the mechanisms causing DNA damage, mutations, and telomere shortening.

KEYWORDS:

Centenarians; Genome stability; Healthy aging; Longevity; Maximum lifespan; Nonagenarians

PMID:
26596548
DOI:
10.1016/j.mrrev.2015.08.001
[Indexed for MEDLINE]

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