Exploring the Connection Between Genes and Lifespan
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Genes and Aging: A Complex Relationship
Aging, often referred to as senescence, is a complex phenomenon marked by physical decline that generally occurs with advancing age. It is influenced by numerous factors, making it a multifaceted challenge.
The aging process impacts all bodily systems, albeit at varying rates and starting points. Ultimately, no bodily function remains untouched as we age. Research is currently investigating various interventions that show promise in positively affecting multiple body tissues. While these findings mainly stem from studies conducted on lab animals, they hint at certain pathways that could significantly influence aging.
As we delve deeper into these pathways, our focus shifts to the specific molecules involved, and further zooming in reveals the genes responsible for coding these molecules. At this stage, researchers examine both the existence of certain gene variants and how gene activity is affected by other genes, molecules, and epigenetic markers—an area that is currently garnering substantial research interest.
Previous studies in mice have pointed to potential genetic "master regulators" associated with aging. More recent investigations have identified both universal and tissue-specific genetic markers related to aging. A recent analysis involving 450 centenarians and 500 control subjects has uncovered several gene variants linked to longevity, particularly those related to cognitive function. Key genes like NFKBIA, CLU, and PRKCH have emerged as significant, with new rare variants continually being discovered.
The Role of Protein-Truncating Variants
Recent research suggests that the size of gene variants, particularly protein-truncating variants (PTVs), may also play a critical role in determining lifespan. This study, which analyzed data from over 350,000 participants in the UK Biobank, found that PTVs—gene variants with shortened coding sequences—are associated with reduced lifespan.
For instance, a stop-gain mutation can create a premature stop signal in a protein-coding sequence, resulting in an incomplete and ineffective protein. The researchers identified four specific PTVs linked to a decreased lifespan: variants in the genes BRCA1, BRCA2, ATM, and TET2. Notably, all four genes are connected to various cancer types, suggesting that their association with shorter lifespans is not entirely unexpected.
Interestingly, these genes had not previously appeared in genome-wide association studies focused on lifespan. Researchers noted that rare PTVs tend to have more pronounced effects on complex traits than common noncoding variants, yet they are often underrepresented in GWAS genotyping arrays. This could be due to the significant selective pressure to eliminate PTVs from the population, rendering them quite rare.
Based on allele frequency, it is suggested that the TET2 variant likely arises from somatic mutations, rather than being inherited. The other three variants are likely inherited from one’s parents.
Conclusion
Thank you for engaging with this exploration of the intricate relationship between our genetic makeup and lifespan. For those interested in broader scientific discussions, consider subscribing to my newsletter, Thinking Ahead, where I delve into various topics in science, technology, philosophy, and occasionally fiction.
The first video, "Is Longevity Genetic?" discusses the genetic factors influencing lifespan, exploring research on longevity-associated gene variants.
The second video, "How Much of Aging is Genetic?" investigates the extent to which genetics determines the aging process, focusing on various studies and findings.