As the population ages and people commonly live into their eighties, nineties and beyond, there is an increasing focus on how we can help people live, not just long lives, but healthy ones. With more and more elderly people needing care in hospitals or residential care homes, finding ways to help people maintain their cognitive powers, and limit frailty and morbidity in later years, will be critical to improving quality of life and reducing the burden on healthcare systems.
One strategy that researchers are using to uncover pathways to these goals, is to study centenarians. These remarkable people who live beyond their 100th year, often with only mild morbidity, appear to have a certain level of resistance to the process of inflammation – which is ultimately the process of aging. Therefore, identifying biological markers to explain this longevity could help us determine the nutritional and genetic secrets of healthy aging.
Using nuclear magnetic resonance (NMR) spectroscopy, a group of researchers studying centenarians from Northern Italy have gone a long way to uncovering such markers.
In a 2013 study, the team, led by Sebastiano Collino (Nestlé Institute of Health Science, Lausanne, Switzerland), used a combined liquid chromatography-mass spectrometry approach with NMR to study blood serum and urine samples from 143 centenarians.
They found that many parameters were significantly different between the centenarians and elderly or young people, including body mass index, cholesterol levels and markers of inflammation, such as C-reactive protein.
What’s more, they found that the centenarians had specific modifications to their metabolic pathways that skewed them towards cellular detoxification and appeared to promote an anti-oxidative response.
To follow-up these results, the same team carried out a further study using NMR metabolomics to profile the serum
of centenarians and compare it with elderly study participants (mean age: 70 years).
The researchers used a Bruker AVANCE III 600 MHz spectrometer to analyze their samples and processed the spectra using Bruker Topspin software. This revealed that the centenarians had a distinct metabolic phenotype.
Of particular note, the oldest subjects had higher levels of phenylalanine, a product of amino acid metabolism which has anti-inflammatory properties and is used as a treatment for Parkinson’s disease and arthritis. The centenarians also had higher levels of glutamine, an amino acid that can cross the blood-brain barrier to remove the toxic build-up of urea, improving brain functions.
Aside from differences in amino acids, centenarians also had lower levels of a circulating marker called glycerophosphocholine, which emerging research suggests is associated with cell senescence.
This finding is particularly interesting when viewed alongside the researchers’ lipidomics results, which showed that there were 41 different types of lipid that were more abundant among centenarians than elderly subjects. These resulted in a number of biological consequences that point towards an improved ability to maintain healthy cell membranes.
Taken together the results support the notion that, as the researchers write, “from a metabolic point of view centenarians are younger than their chronological age”.
References
Collino S, et al. Metabolic signatures of extreme longevity in Northern Italian centegenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PloS One 2013; 8: e56564.
Montoliu I, et al. Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity. Aging 2014; 6: 9-25.