Is Longevity Primarily Determined by Genetics?

Is longevity primarily determined by genetics?

Check out this answer from Consensus:

While genetics play a crucial role in determining longevity, it is not the sole factor. The genetic basis of longevity is complex and involves multiple genes with small effects, influenced by environmental and lifestyle factors. Future research should continue to explore the intricate gene-environment interactions and the population-specific genetic factors that contribute to longevity.

Longevity, the ability to live a long life, is a complex trait influenced by a myriad of factors. While lifestyle and environmental factors play significant roles, the genetic component of longevity has been a subject of extensive research. This article explores whether longevity is primarily determined by genetics, drawing on findings from various studies.

Genetic Contributions to Longevity

Several studies have highlighted the genetic basis of longevity. Research indicates that certain genes are consistently associated with longer lifespans. For instance, the APOE and FOXO3A genes have been identified as significant contributors to longevity across multiple studies1 2 4 5. These genes are involved in cardiovascular health, which is crucial for achieving a longer life.

Genome-Wide Association Studies (GWAS)

GWAS have been instrumental in identifying genetic loci associated with longevity. Despite the complexity of the trait, some genetic variants have been consistently linked to longer lifespans. For example, the APOE ε2 allele is associated with increased longevity, while the APOE ε4 allele is linked to reduced lifespan2 5. Additionally, other loci near genes such as GPR78 have been implicated in longevity2.

Population-Specific Genetic Factors

The genetic determinants of longevity can vary significantly between populations. Studies suggest that population-specific genes may play a more substantial role in longevity than those shared across different populations1 7. This variability underscores the importance of considering genetic diversity in longevity research.

The Role of Gene-Environment Interactions

Longevity is not solely determined by genetics; it is also influenced by gene-environment interactions. The dynamic interplay between genetic predispositions and environmental factors, such as diet, lifestyle, and socioeconomic status, significantly impacts lifespan1 6 7. For instance, early-life nutrition and access to resources can modulate the expression of longevity-related genes6.

Sex and Age-Dependent Genetic Effects

Research has shown that the genetic influence on longevity can be sex- and age-dependent. Certain genetic variants may have different effects on lifespan depending on the individual’s sex and age6. For example, some longevity loci are only detectable in older individuals or exhibit sex-specific effects6.

Polygenic Nature of Longevity

Longevity is a polygenic trait, meaning it is influenced by multiple genes, each contributing a small effect. Meta-analyses have identified several genetic polymorphisms associated with exceptional longevity, but the effect sizes are generally modest5 8. This polygenic nature suggests that a complex interplay of many genes, rather than a few major ones, determines longevity.

 

 

Is longevity primarily determined by genetics?

David Gems has answered Near Certain

An expert from University College London in Biology

There is no single answer to this question, since it can be construed in different ways. If one takes it to mean: are the differences in lifespan between individual people primarily determined by genetics, then the answer is “extremely unlikely”, for reasons given by other contributors (for example Janet Thornton). But considering the word longevity in the sense of having a long life, the question could also mean: are the upper limits of longevity in humans as a species primarily determined by genetics, in which case the answer is “near certain”. For example the maximum lifespan of human beings is approximately twice that of our closest relatives among the higher primates, such as chimpanzees and gorillas. That this is determined by genetics is “near certain”. So my answers are: “extremely unlikely” and “near certain”. But since I am not permitted to choose both (which is a flaw in this site), I will choose the latter so as to answer the second question, since others have already answered the first.

 

Is longevity primarily determined by genetics?

Vincent Geli has answered Unlikely

An expert from Cancer Research Center of Marseille in Oncology, Cell Biology

Aging is a complex process that depends from our ability to renew, repair, and regenerate our tissues that undergo/accumulate multiple dommages with age. Our ability to renew our tissues with age depends on our ability to sustain the functions of our stem cell with aging. This is determined by genetics and in particular by the length of our telomeres.

Along the same line, the proper functions of our tissue depends on our ability to maintain the genome integrity of the cells forming our tissues. The DNA repair machineries are encoded by genes and therefore their efficiency are also determined by genetics. Now, aging is strongly dependent of the numerous damages suffered by our cells and that remain unrepaired with age. Therefore longevity is determined by genetics (and epigenetic) and by the environment and behaviors.

 

Is longevity primarily determined by genetics?

Cornelie Nienaber-Rousseau has answered Unlikely

An expert from North-West University in Nutrition

Candidate gene and large-scale genome-wide association studies (GWAS) have made significant strides in understanding the genetic basis of aging and longevity in humans. These studies have identified numerous genetic loci – specific locations on chromosomes – that are influential in determining key aging traits, including overall lifespan. The Apolipoprotein E (APOE) and Forkhead Box O3 (FOXO3A) genes have consistently been association with longevity in GWAS (1, 2). However, longevity is a multi-trait loci (3). This suggests that there are common genetic pathways influencing various aspects of aging, from specific diseases to overall lifespan. For example, a genetic variation that increases the risk for a condition like heart disease might also be involved in other aging processes or diseases.

Studies show low to moderate heritability estimates for age at death that range from 15 to 30% (4-7). The heritability of lifespan increases at more extreme ages (8) for instance the heritability of living past 85 years is as high as 40% (9). The significant missing heritability (60-85%) highlights the combined influence of genetics and environmental factors. Longevity is influenced by a complex interplay of factors, where genetics does play a crucial role but is not the sole determinant. Recently Ni et al. (10) examined the influence of various factors on longevity using a Mendelian randomization approach. Analyzing data from over 36,000 individuals, they reported significant associations between 13 risk factors and longevity. Notable findings include the impact of smoking, education, blood pressure, venous thromboembolism, obesity, body mass index (BMI), body size at age 10, type 2 diabetes and blood cholesterol levels. The study concluded that BMI significantly influences longevity through pathways including blood pressure, lipid levels and type 2 diabetes, highlighting BMI as a critical target for health and longevity improvement strategies. Therefore, while genetics provides a foundation for lifespan, it is the lifestyle choices and external environmental factors that largely shape how long an individual might live.

For a comprehensive understanding of the role of genetics in longevity, in addition to my current response, please also see my detailed exploration of the impact of lifestyle choices and behaviors on life expectancy in my Q&A post at nutrition-unveiled.ghost.io.

1.           Broer L, van Duijn CM. GWAS and meta-analysis in aging/longevity. Longevity Genes: A Blueprint for Aging. 2015:107-25.
2.           Broer L, Buchman AS, Deelen J, Evans DS, Faul JD, Lunetta KL, et al. GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy. The Journals of Gerontology: Series A. 2014;70(1):110-8.
3.           Melzer D, Pilling LC, Ferrucci L. The genetics of human ageing. Nature Reviews Genetics. 2020;21(2):88-101.
4.           Herskind AM, McGue M, Holm NV, Sörensen TI, Harvald B, Vaupel JW. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Human genetics. 1996;97:319-23.
5.           McGue M, Vaupel JW, Holm N, Harvald B. Longevity is moderately heritable in a sample of Danish twins born 1870–1880. Journal of gerontology. 1993;48(6):B237-B44.
6.           Kerber RA, O’Brien E, Smith KR, Cawthon RM. Familial excess longevity in Utah genealogies. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2001;56(3):B130-B9.
7.           Mitchell BD, Hsueh WC, King TM, Pollin TI, Sorkin J, Agarwala R, et al. Heritability of life span in the Old Order Amish. American journal of medical genetics. 2001;102(4):346-52.
8.           Hjelmborg Jv, Iachine I, Skytthe A, Vaupel JW, McGue M, Koskenvuo M, et al. Genetic influence on human lifespan and longevity. Human genetics. 2006;119:312-21.
9.           Murabito JM, Yuan R, Lunetta KL. The search for longevity and healthy aging genes: insights from epidemiological studies and samples of long-lived individuals. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2012;67(5):470-9.
10.       Ni X, Su H, Lv Y, Li R, Liu L, Zhu Y, et al. Modifiable pathways for longevity: A Mendelian randomization analysis. Clinical Nutrition. 2023;42(6):1041-7.

 

Is longevity primarily determined by genetics?

Ken Parkinson has answered Uncertain

An expert from Queen Mary University of London in Oncology, Anti-Ageing, Cell Biology

I think to some extent it is as my own family on my father’s side are consistently long lived and many groups are trying to understand this by sequencing the DNA of centenarians and supercentenarians and performing genome-wide analysis to look for linked loci. My father is 91 and still is fairly active and is not even completely grey. Puzzling since telomere length is reputed to be inherited through the paternal line  I have very short age-adjusted telomere length. However, I am 68 and ran 5km in 27 minutes last week so see above.

 

Is longevity primarily determined by genetics?

Evandro Fei Fang has answered Likely

An expert from University of Oslo in Anti-Ageing, Alzheimer’s Disease

Yes. Speaking of species, that is the genetic codes that decide a maximum lifespan of mice is 3 years and which can be extended to 30 years in the naked mole rat. 

 

Is longevity primarily determined by genetics?

Dot Bennett has answered Uncertain

An expert from St George’s, University of London in Cell Biology, Skin Cancer, Oncology

Uncertain. I’m not sure if we really know as to “predominantly” at present, although there are clearly some genetic factors, both positive and negative. There are also clearly environmental factors.

 

Is longevity primarily determined by genetics?

Marco Demaria has answered Extremely Unlikely

An expert from University Medical Center Groningen in Cell Biology, Anti-Ageing

Certainly not. Environment and lifestyle are extremely important determinants.

 

Is longevity primarily determined by genetics?

Valery Krizhanovsky has answered Unlikely

An expert from Weizmann Institute of Science in Cell Biology, Anti-Ageing

There is solid evidence that genetic factors can influence longevity. However, on the individual person basis the primary determinant would most probably be environmental and not genetic. Please take responsibility for your health.

 

Is longevity primarily determined by genetics?

Lorna Harries has answered Unlikely

An expert from University of Exeter in Genetics, Cell Biology

No. Genetics definitely plays a part, but lifestyle and environment play an equally important role. Genetics can set you up for a long life, but you then need to do the right things to realise that.

 

Is longevity primarily determined by genetics?

‪Gerardo Ferbeyre has answered Uncertain

An expert from Université de Montréal in Biochemistry, Anti-Ageing

The fact that longevity is so variable across species indicates a strong genetic component. Aging itself could be mostly determined by the environment and longevity, defined as the mechanism that prevent aging, by genes. Whether aging itself is genetically determined is still unknown.

 

Is longevity primarily determined by genetics?

Janet Thornton has answered Extremely Unlikely

An expert from European Bioinformatics Institute in Bioinformatics, Anti-Ageing, Cell Biology

No. Genetics accounts for less than 30% of the effect – but it is true that longevity tends to run in families – ie some families have many very old people!

 

Is longevity primarily determined by genetics?

Nazif Alic has answered Unlikely

An expert from University College London in Genetics, Anti-Ageing, Cell Biology

The variation in longevity of individuals within a species can often be attributed to environment. In humans, the genetic contribution to longevity is about 15%. However, the between species variation is mostly thought to be genetic.