Have you ever wondered why some people live longer than others? While a healthy lifestyle is the most crucial and essential aspect to promoting longevity and healthspan, genetics and family history also play a role. Genetics and family history influence an individual’s susceptibility to diseases of aging and overall lifespan, but for most people, not as much as you may think. In this article, we will explore the impact of genetics and family history on longevity and healthspan, providing actionable guidance for readers.
Impact of Genetics on Longevity: What Studies on Centenarians Revealed
Longevity is influenced by genetics, which was once thought to account for 20-30% of the variation in lifespan (Herskind et al., 1996), but more recent studies have argued that it only accounts for 10% (Ruby et al., 2018). Essentially, this means that lifestyle and environment account for as much as 90% of one’s longevity.
Where genetics may take a larger role in contributing to longevity is for the longest lived people: centenerians (100-109) and supercentenarians (110+). Studies have identified several genetic variants associated with longevity, including the FOXO3A gene, which regulates cell death and DNA repair (Willcox et al., 2008). Additionally, genetic variants affecting the insulin/IGF-1 signaling pathway have been linked to longevity (Deelen et al., 2011). These findings suggest that genetic variants affecting critical cellular processes play a role in determining lifespan. However, these genes are only part of the story for the world’s longest lived people and don’t fully explain how they are consistently 20 to 40 years behind their peers (remember, slower is better!) in the aging process.
Impact of Family History on Longevity
Family history is a consideration when predicting one’s lifespan. People with parents or siblings who live to old age are more likely to live longer than those without such a family history (Newman et al., 2010). Studies have shown that the children of long-lived parents have a 20-30% lower mortality rate than those without long-lived parents (Seshadri and Wolf, 2007). Moreover, siblings of centenarians have a 2-3 fold higher chance of living to 90 years or older than the general population (Perls et al., 2002). These findings suggest that longevity runs in families and that familial factors contribute to lifespan.
However, it’s important to note that this does not mean it’s predominantly based on genetics. Other factors such as education, lifestyle and environment – which accounts for the majority of one’s longevity – also tend to run in families. If your relatives weren’t living pro-longevity lifestyles, you have the power to buck that trend and live substantially longer and healthier than your relatives.
Family History, Genetics, and Healthspan: Impacts on Cancer, Alzheimer’s and Other Diseases of Aging
Healthspan refers to the length of time an individual lives in good health, free from diseases and disabilities of aging. Genetics and family history play a role, albeit limited, in determining healthspan. Studies have shown that individuals with a family history of diseases of aging, such as cancer, cardiovascular disease, and Alzheimer’s disease, are at higher risk of developing these conditions (Kuchenbaecker et al., 2017). For example, a family history of breast cancer increases a woman’s risk of developing the disease by 2-4 fold (Mavaddat et al., 2019).
Similarly, a family history of cardiovascular disease increases the risk of developing the condition by 50-60% (Lloyd-Jones et al., 2010). These findings suggest that genetics and family history contribute to an individual’s risk of developing diseases of aging, which can impact healthspan. For this reason, we suggest that you pay particular attention to lifestyles that can reduce the risks for these diseases if they run in your family – and to do so now, not to wait.
While genetics and family history play a crucial role in determining lifespan and healthspan, there are actionable steps individuals can take to promote longevity and healthspan.
Adopt a Longevity Lifestyle
Adopting the NOVOS longevity lifestyle, including regular exercise, a pro-longevity diet, and avoiding smoking and excessive alcohol consumption, can promote longevity and healthspan (Willcox et al., 2008). Studies have shown that individuals who follow a longevity lifestyle live longer and have a lower risk of developing diseases of aging (Li et al., 2020).
Get Regular Health Checkups
Regular health checkups can help detect diseases of aging early, improving the chances of successful treatment and reducing the impact of these conditions on healthspan. Individuals with a family history of diseases of aging should consider more frequent health checkups and screening tests to detect these conditions early, as well as to proactively research and live lifestyles that minimize the odds of those specific diseases.
Consider Genetic Testing
Genetic testing can help identify genetic variants associated with diseases of aging, allowing individuals to take proactive steps to reduce their risk of developing these conditions. Genetic testing can also provide valuable information for family planning, as individuals can learn about the likelihood of passing on genetic conditions to their children.
However, it is essential to keep in mind that genetic testing has limitations and may not provide a complete picture of an individual’s risk of developing diseases of aging. Genetic variants are only one factor contributing to disease risk, and environmental factors and lifestyle play a far larger role for most of us.
Hallmarks of Aging Impacted by Genetics and Family History
The 12 hallmarks of aging are a set of biological processes that contribute to aging and age-related diseases. Although more than 90% of aging is dictated by lifestyle and environment, for the 10% that’s contributed by genetics, family history can impact several of these hallmarks, including:
Mitochondrial Dysfunction: Genetic variants affecting mitochondrial function can contribute to cellular aging and the development of age-related diseases (Dai et al., 2019).
Cellular Senescence: Familial factors and genetic variants can contribute to the accumulation of senescent cells, which promote inflammation and tissue damage (Childs et al.,2015).
Loss of Proteostasis: Genetic variants affecting protein quality control mechanisms can contribute to the accumulation of damaged proteins, leading to cellular dysfunction and disease (Ciechanover and Kwon, 2015).
Altered Cellular Communication: Genetic variants affecting cell signaling pathways can disrupt cellular communication, contributing to tissue dysfunction and disease (Gough et al., 2020).
Genomic Instability: Familial factors and genetic variants affecting DNA repair mechanisms can contribute to the accumulation of DNA damage, leading to mutations and the development of age-related diseases (Vijg and Campisi, 2008).
Epigenetic Alterations: Familial factors and genetic variants affecting epigenetic modifications can alter gene expression patterns, contributing to age-related diseases (Horvath, 2013).
Telomere Shortening: Genetic variants affecting telomerase activity can contribute to telomere shortening, which is associated with cellular aging and the development of age-related diseases (Blackburn et al., 2015).
Deregulated Nutrient Sensing: Genetic variants affecting nutrient sensing pathways can contribute to metabolic dysfunction, leading to the development of age-related diseases (Kennedy and Lamming, 2016).
Stem Cell Exhaustion: Familial factors and genetic variants affecting stem cell function can contribute to tissue degeneration and the development of age-related diseases (Liu and Rando, 2011).
Disabled Macroautophagy: Genetic variants affecting autophagy mechanisms can contribute to the accumulation of damaged organelles and proteins, leading to cellular dysfunction and disease (Klionsky et al., 2016).
Inflammaging: Familial factors and genetic variants affecting inflammatory signaling pathways can contribute to chronic inflammation, promoting tissue damage and disease (Franceschi and Campisi, 2014).
Microbiome Dysbiosis: Familial factors and genetic variants affecting the gut microbiome can contribute to dysbiosis, promoting inflammation and metabolic dysfunction (Tremaroli and Bäckhed, 2012).
Genetics, Family History and Longevity
Genetics and family history play a role in determining longevity and healthspan. While genetics and family history cannot be changed, adopting a healthy NOVOS longevity lifestyle, getting regular health checkups, and considering genetic testing, will help promote longevity and healthspan significantly more so than genetics in the vast majority of people. Furthermore, understanding the hallmarks of aging impacted by genetics and family history can provide valuable insights into potential areas of focus for personalized preventative strategies to reduce the risk of developing age-related diseases.
- Ruby, J., Wright, K., Rand, K., et al. (2018). Estimates of the Heritability of Human Longevity Are Substantially Inflated due to Assortative Mating. Genetics, 210(3), 1109-1124.
- Blackburn, E. H., Epel, E. S., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2015). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101(49), 17312-17315.
- Ciechanover, A., & Kwon, Y. T. (2015). Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Experimental & Molecular Medicine, 47(3), e147-e147.
- Dai, D. F., Chiao, Y. A., Marcinek, D. J., Szeto, H. H., & Rabinovitch, P. S. (2014). Mitochondrial oxidative stress in aging and healthspan. Longevity & Healthspan, 3(1), 6.
- Franceschi, C., & Campisi, J. (2014). Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(Suppl_1), S4-S9.
- Gough, N. R., Hattem, G. L., & Fambrough, D. M. (2020). Signaling: cell communication and signaling. Elsevier.
- Holt-Lunstad, J., Smith, T. B., & Layton, J. B. (2010). Social relationships and mortality risk: a meta-analytic review. PLoS Medicine, 7(7), e1000316.
- Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14(10), R115.
- Kennedy, B. K., & Lamming, D. W. (2016). The mechanistic target of rapamycin: the grand conductor of metabolism and aging. Cell Metabolism, 23(6), 990-1003.
- Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., … & Acevedo-Arozena, A. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy, 17(1), 1-382.
- Liu, L., & Rando, T. A. (2011). Manifestations and mechanisms of stem cell aging. Journal of Cell Biology, 193(2), 257-266.
- Tremaroli, V., & Bäckhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature, 489(7415), 242-249.
- Vijg, J., & Campisi, J. (2008). Puzzles, promises and a cure for ageing. Nature, 454(7208), 1065-1071.
- Zhang, J., Rane, G., Dai, X., Shanmugam, M. K., Arfuso, F., Samy, R. P., … & Sethi, G. (2019). Ageing and the telomere connection: An intimate relationship with inflammation. Ageing Research Reviews, 54, 100917.
*We are currently working on providing full citations, which will be available soon.