There’s a lot that can be done to increase longevity: maintain a healthy diet, exercise regularly, prioritize sleep, manage stress and mental health, avoid harmful substances, cultivate social connections, practice positivity, and pay attention to cellular health and micronutrition. But once extrinsic factors — such as violence, accidents, infections, and similar events — are taken out of the equation, genetics plays its full role in determining how long (and how healthy) a lifespan may be. Researchers are working to better understand this role, and their findings are already having an impact on what can be done to ensure a longer, healthier, more satisfying life.

Fifty-Fifty

Longevity heritability in humans is difficult to establish, mainly because it takes a long time to collect data on human lifespans. Even when those data are available for analysis, many different factors contribute to mortality, and distinctions must be made between extrinsic and intrinsic mortality.

The Weizmann Institute of Science recently conducted an analysis of more than a century’s worth of data from three different Scandinavian twin cohorts — including a dataset of twins who were raised apart — filtering out cases of extrinsic mortality among its subjects, many of whom were born during the late 1800s and early 1900s, when external factors were much more likely to result in early death.

With those members of each cohort excluded, heritable longevity rose dramatically, from the 20-25% scientists had cited for decades to about 50%. It’s a number that correlates with many other human traits, pointing to the conclusion that roughly half of our lifespan may be determined by our genes.

Beating the Odds

Knowledge is power, and understanding that aging has a strong genetic component is the first step toward altering the blueprint and shifting the odds in the direction of increased longevity.

Human aging is characterized by a progressive decline in structure and function of organs and tissues, a process that significantly increases the risk of many chronic diseases. Can science develop the kinds of interventions required to delay aging? Many scientists believe the answer is yes.

Gene therapy, a medical technique that modifies a patient’s genes to treat or prevent disease, works by adding, correcting, or silencing specific genes. Rather than managing symptoms with medication, gene therapy targets the genetic root of disease by introducing a healthy copy of a gene, correcting a defective gene, or reducing the impact of a harmful gene at the cellular level, restoring normal function or preventing disease progression. While traditional drugs typically require ongoing administration, gene therapy has the potential to offer long-lasting effects with a single treatment.

In short, by leveraging advanced gene-editing and delivery systems to target the molecular underpinnings of aging, gene therapy holds the potential to reduce the burden of age-associated diseases and promote healthy longevity.

Regenerative Advances Ahead

Fumihiro Sanada, MD, PhD, Shinichiro Hayashi, MD, PhD, FAHA, FESC, and Ryuichi Morishita, MD, PhD, of the Department of Clinical Gene Therapy at Japan’s Osaka University Graduate School of Medicine, explain that the complex biological process known as aging involves a set of interconnected mechanisms called the hallmarks of aging. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, and dysregulated nutrient sensing.

The primary hallmarks of aging are considered the root causes of cellular aging, and interventions targeting these hallmarks — including telomerase gene therapy to counter telomere attrition, NAD+ precursors such as NMN to support DNA repair and genomic stability, partial epigenetic reprogramming with Yamanaka factors to reverse transcriptional aging, and autophagy enhancers like rapamycin to restore proteostasis — have shown promise in preclinical models. Emerging therapeutic strategies, Dr. Sanada, Dr. Hayashi, and Dr. Morishita report, aim to delay or reverse aging by targeting these specific hallmarks.

“Advances in regenerative medicine, gene editing, and organ cross-talk modulation are also contributing to the development of personalized, multi-targeted anti-aging therapies,” they added. “Integration of omics technologies and biomarker research is expected to enhance our ability to monitor biological aging and optimize interventions for healthy longevity.”

What You Can Do

Armed with the knowledge that genetics may account for about half of human longevity potential, genetic science companies have developed DNA tests that can empower individuals to make informed choices that support long-term health and wellbeing. With these scientifically backed reports on genetic predispositions for wellness traits, many people feel free to focus on lifestyle factors they can modify to help optimize their longevity potential.

As longevity science advances and emerging gene therapy solutions become more widespread, patients may find that a health management plan tailored to their genetic profile — combined with genetic insights and targeted therapeutic interventions — is the key to achieving a longer, healthier lifespan.

Research/articles:

Scientists Were Wrong About Lifespan. Your Genes Matter Way More Than We Thought

Heritability of Intrinsic Human Life Span is About 50% When Confounding Factors are Addressed

Genetic and Somatic Trade-Offs Drive Aging

New Clues to Slow Aging? Scientists Use Genetic Rewiring to Increase Lifespan of Cells

Gene Therapy Strategies for Aging Intervention