Some family lineages produce far more long-lived individuals than others with the same background: similar region, culture, wealth, and era. From that we can conclude that some natural genetic variations provide a greater chance of living longer in good health. The present high level view of genetics and aging is that outside of rare and catastrophic mutations, genetic variation has comparatively little influence on survival prior to old age: it's all about lifestyle choices, and to a first approximation those boil down to smoking, exercise, excess fat tissue, and how much you eat. After age 70 or so this changes, and genetic variation plays an ever larger role. Centenarians, those who reach age 100 or more, typically are less impacted by aging at any given age than their less fortunate peers. Aging is damage, they are less damaged, and their genetics has a role in this.
This is the logic that leads a great many researchers to investigate the biochemistry and genetics of centenarians and long-lived families in search of knowledge that can be turned to treatments to slow aging. This is little different to work on calorie restriction mimetics in terms of expected utility, however. It is hard work, a slow, expensive investigation of extremely complex systems that are at present poorly understood. The end result will not be any way to turn back aging, but at best to slow it. Genetic variations that show up more often in centenarians are not a guarantee of comparative longevity, they only swing the odds. There are many people with these genes, and very, very few of them live to be 100 or older. It's just that if you don't have that biochemistry the odds are even more terrible.
I don't want the future of aging research to be an expensive, slow scrabble for ways to slightly slow aging, or to make it slightly more possible to be burdened by a high load of cellular and molecular damage and yet remain alive. The future should be the targeted exploitation of what is known of the root causes of aging, so as to build repair and rejuvenation therapies that can maintain health and youth, and effectively cure age-related conditions in the old. That is the path to meaningful results in terms of more years lived in good health: repair the damage in the system you have, as this is a much more efficient approach in comparison to changing the system to slow its decay.
That doesn't mean that centenarian research is uninteresting, however. It is fascinating stuff. Just bear in mind that it most likely isn't a path to much of use other than greater knowledge of the fine details of the biology of aging. This is knowledge that we arguably have little need of in order to move a long way towards a cure for aging based on repair its known root causes.
Autophagy is a major clearance mechanism that degrades organelles and large protein aggregates to maintain cell survival and protein homeostasis. Although induction of autophagy can promote longevity in experimental models, the question as to whether increased basal levels of autophagy can be associated with human longevity remains open. In this pilot study, we investigated the association between serum concentrations of beclin-1, a key regulator of autophagy, and human exceptional longevity.
Serum beclin-1 was measured in three study groups: 79 healthy centenarians (39 males, aged 100-104 years); 178 non-diabetic patients who had experienced an acute myocardial infarction at a young age (101 males, 28-39 years); and 180 age- and sex-matched healthy young volunteers (103 males, 27-39 years). Healthy centenarians had significantly higher beclin-1 levels compared with both young patients with myocardial infarction and healthy controls, whereas no significant difference was observed between the two groups of young subjects. Our preliminary data suggest that elevated basal levels of autophagy as reflected by high serum beclin-1 levels may be a biomarker of healthy human exceptional longevity.
To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. We identified 130 coding variants that were annotated as "pathogenic" or "likely pathogenic" based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several of these variants are located in genes that harbor actionable incidental findings, according to the recommendations of the American College of Medical Genetics. In addition, we found risk variants for late-onset neurodegenerative diseases, such as the APOE ε4 allele that was even present in a homozygous state in one centenarian who did not develop Alzheimer's disease. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions.
The survival probability of becoming a centenarian (SPBC) is defined as an estimate of the production of centenarians by a population. The SPBC (70) is the survival probability of becoming a centenarian for those aged 70. Significant positive correlations were found between the SPBC (70), and the socioeconomic factors of gross national income (GNI), public expenditure on health as a percentage of gross domestic product (PEHGDP), fixed and mobile telephone subscribers (FMTS) as the standard of living, and improved sanitation facilities (ISF).