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Examples of Genetic Association Studies of Human Longevity

Posted: April 14, 2013 at 2:58 am

A fair number of research groups worldwide are gathering and processing data in search of associations between minor genetic variations and human longevity. As for all studies of long-term human health, this a challenging process: statistics become involved, it is costly to gather data of even moderate quality, and the underlying biology is exceedingly complex. This is illustrated by the fact that comparatively few genetic associations can be validated across different study populations: if you find a genetic polymorphism with a statistically significant association with longevity in Italian lineages, the odds are very good that it won't show up in Asian populations, or even in other Italian study populations, for that matter. The range of minor variation in the human genome is very large, and it seems to be the case that there are many, many tiny genetic contributions to the way in which metabolism interacts with environment to determine natural longevity, most of which differ widely in different populations.

So while the funding lasts, this is a deep well for researchers to work on - just not one likely to produce more than knowledge for the foreseeable future. If you want actual results in terms of therapies to reverse the course of aging, then look to the programs described in the SENS research outline. The research community already knows what needs to be repaired in aged tissue, as the low-level differences between old and young tissue are well enumerated - it is the intricate, enormously complex metabolic dance of progressing from undamaged to damaged that remains an open field of work. The difference between SENS and the mainstream efforts to fully understand aging is the difference between on the one hand making the effort to rust-proof a metal surface and on the other producing a complete and detailed model of how rust progresses and interacts with metal structures at every level, from chemistry through to the physics of forces acting on structures and material strengths. The latter isn't necessary to achieve the goal of prevention once you know what rust is, and indeed will probably prove to cost far more than just preventing the rust.

Here are a couple of illustrative papers from the steady flow of new associative studies of genetics and aging in humans. There will be many more similar results arriving in the years ahead: a lot more money goes towards this sort of work than to any effort to do something about aging.

The functional VNTR MNS16A of the TERT gene is associated with human longevity in a population of Central Italy

Telomerase, encoded by TERT, is the ribonucleoprotein polymerase that maintains telomere ends and it plays a crucial role in cellular senescence. TERT single nucleotide polymorphisms (SNPs) have been associated both with various malignancies and telomere length (TL). The association of TERT SNPs with longevity remains uncertain and varies with ethnicity. Aim of this study was to investigate whether the functional variable number of tandem repeat (VNTR) MNS16A of TERT is associated with longevity.

MNS16A genotypes have been determined for 1072 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes. MNS16A appears associated to longevity. The MNS16A*L allele is significantly underrepresented in Age Class 3 compared to Age Class 2. The concomitant significant telomere cross sectional attrition rate observed for L*/L* genotype suggests that this polymorphism could influences human longevity by affecting TL.

Common polymorphisms in nitric oxide synthase (NOS) genes influence quality of aging and longevity in humans

Nitric oxide (NO) triggers multiple signal transduction pathways and contributes to the control of numerous cellular functions. Previous studies have shown in model organisms that the alteration of NO production has important effects on aging and lifespan. We studied in a large sample (763 subjects, age range 19-107 years) the variability of the three human genes (NOS1, -2, -3) coding for the three isoforms of the NADPH-dependent enzymes named NO synthases (NOS) which are responsible of NO synthesis.

We found that gene variation of NOS1 and NOS2 was associated with longevity. In addition NOS1 rs1879417 was also found to be associated with a lower cognitive performance, while NOS2 rs2297518 polymorphism showed to be associated with physical performance. Moreover, SNPs in the NOS1 and NOS3 genes were respectively associated with the presence of depression symptoms and disability, two of the main factors affecting quality of life in older individuals. On the whole, our study shows that genetic variability of NOS genes has an effect on common age related phenotypes and longevity in humans as well as previously reported for model organisms.


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