How Does Caloric Restriction Enable Longevity? Part III: When genes matter (and when they don’t)

Healthy Aging

When and how genes influence our longevity

It’s International Longevity Month, which coincides well with a big study published in Nature that evaluated how dietary restriction extends longevity. Over the past two weeks, we covered this study’s findings that overall body resilience is THE key to living longer. For our last week focusing on this latest study, let’s go genetic.

Alrighty – one last time: Key findings from this study.

Di Francesco et al. evaluated the effects of lifelong dietary restriction and intermittent fasting among 1,000 genetically varied mice. While studying which effects, such as body weight and blood values, of these dietary practices had the most influence on longevity, they found the following:

• Serious dietary restriction = longer life. Of the different dietary interventions, consistently restricting daily dietary calories by 40% throughout life resulted in the longest lives.
• Resilience = longer life. Maintaining healthy body weight, red blood cells, and immune responses with age had the greatest influence on longevity.
• Weight loss and lower glucose ≠ longer life. While body weight loss and improved glucose handling did occur among many dietary restricted mice, these effects did not influence longevity.
• Genes win, at least over dietary restriction. Genetics had a significant influence on which dietary restricted mice had the longest lifespan.

So, let’s talk about the strong influence genes had on longevity.

Explaining varying longevity outcomes among dietary-restricted individuals.

Although restricting the dietary intake of mice by 40%  extended overall longevity, not all mice in this group lived longer. This variation was particularly apparent in Di Francesco et al.’s study thanks to their smart use of:

• A large study population of 1,000 mice
• Genetically diverse mice

These two factors allowed the team to evaluate how and why some dietary restricted mice live longer… while others did not. Previously, we shared that the following three key markers of resilience had the greatest influence on longer life: stronger red blood cells, maintained balanced immunity, and maintained healthy body weight (especially avoidance of weight loss during their oldest years).

Additionally, the team found that a mouse’s individual genetics had a stronger influence on longevity than dietary restriction itself.

The strong role of genes + longevity is not really a surprise.

You were probably not blown away by that last point, right? We all know families that have people who have “good genes” and are more likely to live longer. Our co-founder Eric’s grandmother lived to 104. Eric’s mom, who is 80 years old, is still skiing black diamond runs.

While black-diamond skiing mice would make for amazing TikTok content, it was important enough for Di Francesco et al to show the following:

• If a mouse had “longevity” genes, no matter its diet, it was most likely to live longer.
• If a mouse had the right “resilience-supporting” genes and it went on a severely restricted diet, it was more likely to live longer than other mice.
• If a mouse didn’t have the right “resilience-supporting” genes and it went on a severely restricted diet, it wasn’t as likely to experience extended longevity.

So, is this good or bad news? Well, it depends.

The relevance of mouse genes + dietary restriction + longevity to you.

As shared in an invited editorial in Nature on this latest paper, Dr. Schork noted that “the mechanisms behind the possible benefits of… dietary restriction, are more complex than previously thought.”

Here’s the good news:

• If you have strong overall longevity-supporting genes, your chances of living longer go up.
• If you have genes that support resilience (aka stronger red blood cells, maintained balanced immunity, and maintained healthy body weight) in the face of challenges, your chances of living longer go up, too.

Here’s the less-than-good-news:

If you don’t have strong longevity or resilience-supporting genes, your chances of living longer, even using dietary restriction or intermittent fasting, are lower. At least according to this latest study.

Sounds like Eric needs to treat his mom and her longevity genes to dinner this week (and every week).