The expression of these five genes has been associated with healthy aging and longevity and their mutations with morbidity and mortality.

This story does not include health advice. It is for information, inspiration, and awareness purposes.

Photo byNational Cancer InstituteonUnsplash

One area of my research interest is exploring the influence of genes on health and longevity. As a postdoctoral researcher, I have been fascinated by specialized scientists in genetics and longevity who have pinpointed specific genes that play pivotal roles in aging over recent decades.

Researchers increasingly believe optimizing these genes' expression through lifestyle modifications and medical interventions can slow aging and promote a more youthful state. I linked to many credible sources.

Clinicians utilize these genes as biomarkers to assess health and longevity prospects. Some longevity clinics use lifestyle adjustments and pharmaceutical interventions to enhance their clientele's health and lifespan. However, as documented in this 2022 paper, no universal biomarker estimates overall health status and longevity prospects yet.

The critical point of my story is to express these known longevity genes to create epigenetic effects for a healthier and longer life. Epigenetics studies changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence.

I also focus on the promise of genetic interventions, the deliberate manipulation of genetic material using various techniques to modify specific traits and treat genetic disorders.

Updated Onim Gene Map Statistics inform that 7,503 genetic disorders have been reported, and more are constantly being described. I documented a recent case study making a deaf person hear sound for the first time.

In this story, I will provide an overview of the longevity genes I studied for personal and professional reasons without using too many scientific and technical details. I aim to inform and inspire you to consider these genes when designing your lifestyle for better health and graceful aging. First, I will provide high-level information about genetics so that you can understand the key points of the critical genes I cover.

What are genes and DNA in simple terms?

A gene is a fundamental unit of heredity that carries the instructions for building, maintaining, and regulating our traits (characteristics). Genes are located within cells in the nucleus, a specialized compartment that houses the cell’s genetic material, including DNA.

Some people confuse genes with DNA. Genes comprise DNA (deoxyribonucleic acid), a large molecule that carries the genetic instructions necessary for our growth, development, functioning, and reproduction. Each cell in the body contains a complete set of genes, collectively determining our characteristics and functions.

Genes are specific regions of DNA that contain instructions for making proteins or functional RNA molecules. While DNA is the larger molecule that contains an organism's entire genetic blueprint, genes are smaller segments that encode specific biological functions.

Each gene consists of a specific sequence of nucleotides, the building blocks of DNA. These nucleotides encode the information needed to produce a functional product, typically a protein or RNA molecule.

The Human Genome Project has estimated that humans have between 20,000 and 25,000 protein-coding genes. Every person has two copies of each gene, one inherited from each parent.

Most genes are the same in all people, but a small number (less than 1%) differ slightly between people. Alleles are forms of the same gene with minor differences in their DNA base sequence, which contribute to each person’s unique features.

Some genes do not code for proteins. These non-protein-coding genes control the expression of protein-coding genes, regulate various cellular processes, and cause epigenetics. Examples of non-coding genes include tRNA, rRNA, miRNA, lncRNA, and more.

What does gene expression mean?

Gene expression is the process through which the information stored within a gene is used to produce a functional gene product, like a protein. This process involves transcription, where the gene’s DNA sequence is copied into an mRNA molecule, and translation, where ribosomes decode the mRNA to assemble the corresponding protein.

In simpler terms, gene expression is how the instructions in our genes are used to make proteins, which are essential for the functioning of our bodies. It’s like following a recipe to cook a meal.

First, the gene’s instructions are copied into an mRNA molecule in transcription. Then, ribosomes decode this mRNA to build the protein. This process is vital for developing, growing, and maintaining our cells and tissues and influences our health and well-being.

Gene expression is fundamental in determining the characteristics and functions of our cells, tissues, and organs. It is a crucial aspect of molecular biology and genetics.

Gene expression is tightly regulated and can be influenced by various factors, such as environmental cues, developmental stage, and cellular signaling pathways. It plays a fundamental role in determining the characteristics and functions of cells and organisms.

What does gene mutation mean, and what are the consequences?

A gene mutation is a permanent alteration in the genetic code of a DNA molecule. Various factors can cause this change, such as errors during DNA replication and exposure to radiation, chemicals, or viruses.

Mutations can result in different outcomes, like no effect, a change in the gene's function, or loss of function. Depending on their location and impact, genetic mutations can lead to genetic disorders or diseases or contribute to evolutionary changes.

Mutations in genes can alter their function, which may impact various physiological processes, contribute to the development of diseases, or adversely affect aging and longevity.

However, the consequences of mutations can vary depending on the specific gene, the type of mutation, and other factors we still need to discover. These genes (Klotho, FOXO3, SIRT1, APOE, and BRCA) can also undergo mutations. Therefore, I highlight them in this story.

How about gene polymorphism of these?

Gene polymorphism is variations in the DNA sequence within a population, where each variant is present in at least 1% of the population. Klotho, FOXO3, SIRT1, APOE, and BRCA can exhibit polymorphisms.

Polymorphisms in these genes refer to variations in their DNA sequences that occur naturally within a population. These variations can include single nucleotide changes (SNPs), insertions, deletions, or other structural alterations in the DNA sequence.

Polymorphisms in these genes can influence their function, expression levels, or interactions with other molecules, potentially affecting physiological processes and disease susceptibility.

Depending on their location within the genome and their impact on gene function, polymorphisms may be harmless, have subtle effects, or be associated with increased or decreased risk of certain conditions. Studying gene polymorphisms is necessary to understand the genetic basis of complex traits and diseases and develop personalized healthcare approaches.

I documented my research into gene polymorphisms or mutations for MTHFR to prevent cardiovascular issues within the vitamin B12 context.

An Overview of Five Longevity Genes

In this section, I summarize the key points of Klotho, FOXO3, SIRT1, APOE, and BRCA genes based on literature reviews and highlight various lifestyle factors that can influence the expression of genes.

1 — Klotho

This gene was named after the Greek Fate and is responsible for spinning the thread of life, as Klotho plays a crucial role in several physiological processes. In Greek mythology, the Fates (the Moirai) were a trio of goddesses responsible for controlling the destiny of mortals and gods.

Klotho expression has gained significant interest due to its potential implications for health and longevity. Klotho is primarily expressed in the kidneys and brain, although it is also found in other tissues. It exists in membrane-bound and soluble forms, with the latter acting as a hormone.

Klotho is involved in diverse biological functions, such as regulating phosphate and calcium metabolism, modulating insulin signaling, suppressing oxidative stress, and promoting autophagy. Its anti-aging properties stem from its ability to suppress insulin/IGF-1 signaling, which is associated with longevity.

Studies in animal models have shown that Klotho overexpression extends lifespan and protects against age-related diseases such as cardiovascular disease, neurodegeneration, and cancer. For example, interestingly, this paper reviewing its impact is titled “Klotho: An Elephant in Aging Research.”

Variations in the Klotho gene have been associated with differences in cognitive function, bone mineral density, and susceptibility to age-related disorders in humans. The neuroprotective role of Klotho on dementia was documented in a 2023 paper.

Furthermore, these studies show that higher blood levels of soluble Klotho correlate with better cognitive function, lower cardiovascular events, and increased longevity in some populations.

Understanding Klotho's role in human health and aging has significant implications for developing interventions to promote healthy aging and prevent age-related diseases. Strategies to enhance Klotho expression or mimic its effects could potentially lead to the development of novel therapeutics for age-related conditions.

Klotho Lifestyle Factors: Exercise, fasting, caloric restriction, meditation.

2 — FOXO3

FOXO3 (Forkhead box protein O3) has attracted considerable attention in longevity and aging research due to its potential implications for our health and lifespan. Named after the “Forkhead” family of transcription factors, FOXO3 plays a pivotal role in regulating various biological processes critical for longevity.

While primarily known for its involvement in the insulin/IGF-1 signaling pathway, FOXO3 also influences diverse cellular functions, such as DNA repair, apoptosis, oxidative stress response, and metabolism. Various cellular signaling pathways tightly regulate its activity, allowing it to modulate gene expression in response to environmental stimuli and stressors.

Numerous studies in model organisms have demonstrated that FOXO3 activation can extend lifespan and enhance stress resistance, highlighting its significance in aging biology.

Variations in the FOXO3 gene have been associated with differences in longevity, age-related diseases, and cognitive function. People with specific FOXO3 variants may exhibit enhanced resilience to age-related disorders ( cardiovascular disease and cancer).

FOXO3 has been implicated in regulating stem cell function and tissue regeneration, suggesting its potential role in maintaining tissue homeostasis and promoting healthy aging.

Understanding the mechanisms underlying FOXO3's mediated effects on aging and longevity holds promise for developing interventions to enhance healthspan and combat age-related diseases. Strategies targeting FOXO3 activation or modulation could offer novel avenues for promoting healthy aging and improving the overall quality of life in aging populations.

FOXO3 Lifestyle Factors: Exercise, caloric restriction and fasting.

3 — SIRT1

SIRT1 (Sirtuin 1) has gained significant attention in longevity and aging research, especially in the context of neurodegeneration. Belonging to the sirtuin family of proteins, SIRT1 is a histone deacetylase enzyme that regulates various cellular processes associated with aging and longevity.

One of its primary functions is the modulation of gene expression through histone deacetylation, which can influence diverse biological pathways such as DNA repair, apoptosis, inflammation, and metabolism.

SIRT1 activity is influenced by nutrient availability, oxidative stress, and cellular energy status, allowing it to respond dynamically to environmental cues and stressors.

Studies in model organisms have revealed that SIRT1 activation can extend lifespan and confer protection against age-related diseases. In humans, SIRT1 has been implicated in physiological processes like energy metabolism, insulin sensitivity, stress response, and inflammation, suggesting its potential role in promoting healthy aging.

This 2021 Nature paper documented that genetic variations and mutations in the SIRT1 gene have been associated with differences in longevity and susceptibility to age-related health conditions, highlighting its significance in human aging biology.

This paper in Cell documented that SIRT1 activation has been linked to the beneficial effects of caloric restriction and exercise on longevity and health span. This further highlights its potential as a target for therapeutic interventions promoting healthy aging.

Understanding the complex mechanisms underlying SIRT1-mediated effects on aging and longevity could lead to developing novel strategies to enhance lifespan and mitigate age-related diseases in human populations. SIRT1 activity and expression levels may be valuable biomarkers for assessing individual aging trajectories, especially for men.

SIRT1 Lifestyle Factors: fasting and caloric restriction. Resveratrol might activate SIRT1, possibly enhancing its anti-aging properties, but preliminary findings haven’t been replicated yet.

4 — APOE

APOE (Apolipoprotein E) has garnered considerable interest in longevity and aging studies due to its significant impact on our health and lifespan. APOE encodes a protein involved in lipid metabolism and transport, particularly in the brain and peripheral tissues. This protein is crucial in regulating cholesterol metabolism, neuronal repair, and inflammation, making it a key player in various physiological processes.

APOE has three significant isoforms: APOE2, APOE3, and APOE4. Each has distinct functional properties and associations with disease risk. APOE4, in particular, has been linked to an increased risk of Alzheimer’s disease and cardiovascular disease, while APOE2 is associated with a reduced risk of these conditions.

Studies have also suggested that the APOE genotype may influence lifespan and cognitive function. APOE4 carriers exhibit accelerated cognitive decline and reduced longevity compared to APOE3 and APOE2 carriers.

The effects of APOE on aging and disease risk are complex and multifaceted, involving interactions with various pathways related to lipid metabolism, neuroinflammation, and synaptic function. Understanding the role of APOE in aging biology is essential for explaining the mechanisms underlying age-related diseases and developing targeted interventions to promote healthy aging and longevity.

APOE Lifestyle Factors: Dietary patterns, such as the Mediterranean diet can enhance APOE expression and reduce cardiovascular disease risk. Regular exercise may also boost APOE expression, lowering the risk of cognitive decline and Alzheimer’s disease. Quitting smoking can help restore APOE’s expression, promoting better health.

5 — BRCA

BRCA (Breast Cancer Gene) has been renowned for its implications in longevity and health since 1994, particularly in cancer susceptibility and genetic predisposition. Located on chromosome 17, BRCA1 codes for a tumor suppressor protein involved in DNA repair and maintaining genomic stability.

Its role in safeguarding against cancer is paramount, as mutations in BRCA1 can significantly increase the risk of breast, ovarian, prostate, and other cancers. This 2022 paper on Frontiers provided therapeutic strategies.

BRCA1 operates within intricate cellular pathways, orchestrating DNA damage repair, cell cycle regulation, and apoptosis. These processes are crucial for preventing the accumulation of harmful mutations. People with BRCA1 mutations are at heightened risk for developing aggressive forms of cancer at earlier ages.

However, BRCA1’s impact extends beyond cancer susceptibility, with emerging evidence linking it to various physiological processes such as cellular metabolism, inflammation, and aging.

BRCA1/2 testing is a pivotal tool for assessing cancer risk and guiding clinical decision-making, empowering individuals and healthcare providers to implement proactive cancer prevention and early detection. Like BRCA1, BRCA2 is also involved in DNA repair processes.

BRCA Lifestyle Factors: Carcinogens like tobacco smoke can affect BRCA expression, increasing the risk of breast and ovarian cancer. A healthy diet and lifestyle, avoiding processed foods and alcohol, can support BRCA function and reduce cancer risk. Regular screening is crucial for managing cancer risk in individuals with BRCA mutations.

How about mTOR and IGF-1 for longevity?

mTOR (mammalian target of rapamycin) and IGF-1 (insulin-like growth factor 1) are signaling pathways rather than individual genes. These pathways involve a complex network of genes, proteins, and cellular processes that regulate various aspects of metabolism, growth, and aging.

The mTOR pathway regulates cell growth, metabolism, and aging. Inhibition of mTOR signaling has been shown to extend lifespan and improve healthspan in various organisms. Fasting or caloric restriction is one intervention that inhibits mTOR.

Insulin-like growth factor 1 (IGF-1) is a hormone that regulates growth and development. In animal models and human observations, reduced IGF-1 signaling has been associated with increased lifespan and improved metabolic health.

Conclusions and Takeaways

These are just a few examples of genes implicated in longevity and aging that we know so far. Research into the genetics of aging is ongoing, and scientists continue to discover new genes and pathways that influence lifespan and healthspan.

The expression of the longevity genes influences various physiological processes and is associated with improved healthspan and lifespan. Further research into its mechanisms of action and potential therapeutic applications holds promise for promoting healthy aging and preventing age-related diseases.

Lifestyle factors can modulate gene expression, promote health and longevity, and reduce the risk of age-related diseases. For example, I fast and exercise to lower the impact of mTOR and IGF-1 on biological aging.

However, genetics also interact with lifestyle factors, and individual responses may vary. Consulting with qualified healthcare professionals can provide personalized recommendations based on genetic predispositions and lifestyle choices.

My story focused on the impact of known longevity genes in inducing epigenetic changes that promote better health and longevity. Epigenetics explores alterations in gene expression or cellular traits driven by mechanisms beyond modifications in the DNA sequence.

Our genetic fate no longer binds us. We are discovering ways to harness our genes to improve our lives.

This means that understanding and leveraging the effects of specific genes associated with longevity can potentially lead to lifestyle and medical interventions that promote better health and a longer lifespan.

Epigenetics reveals how these genes influence gene expression and cellular behavior, offering insights into how we can optimize our well-being through targeted interventions. Aging is inevitable, but graceful aging is possible.

Thank you for reading my perspectives. I wish you a healthy and happy life.

If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.