Pathology


Despite its occasional detractors and debate about how it works (at both global and molecular levels), biogerontologists generally consider calorie restriction (CR) to be A Good Thing™.

CR, as the catechism goes, is the only intervention that significantly increases lifespan in every organism studied. This strict dietary regimen also has other benefits, e.g., modifying adipocyte (fat cell) gene expression to increase insulin sensitivity and thereby fend off late-onset insulin-resistant diabetes.

At the immunological level, too, CR shows great promise, apparently slowing immune system aging by delaying clonal senescence and increasing the effectiveness of response to both previously encountered and novel pathogens.

All the more surprising, then, is the finding that CR increases susceptibility to certain types of infection. Deborah Kristan has demonstrated that chronically food-limited mice are less capable of fighting off a nematode parasite, despite their higher immunoglobulin and eosinophil responses to the infection.

Contrary to predictions, CR mice had more worms than ad libitum-fed mice and the worms from CR mice produced more eggs than worms from ad libitum-fed mice. These data indicate that, despite the evidence that long-term CR enhances traditional measures of immune function, CR may actually increase susceptibility to intact parasite infection.

In other words, despite prior reasons to believe that CR would boost immunity, and evidence from this very study supporting the theory (i.e., the increased immune response), the ultimate result turned out exactly the opposite: CR mice had a higher parasite load, at least in this particular model of infection.

This outcome demonstrates the importance of continuing to drive a field toward the best answers by asking the best questions. “Does CR enhance the immune system?” is a good question, but it’s not as good as “Does it do so in a manner that is functionally relevant?” Kristan didn’t stop at what some would have considered the finish line, but pushed ahead to ask the next question — one whose answer casts quite a different light on CR.

Skepticism, the healthy tendency to test the corollaries of past findings rather than lean back and contently predict them, has great value in science — perhaps even more so in the face of an emerging consensus. While no one (at least, no one responsible) has claimed that CR is a panacea for all ills, it is crucial to temper our enthusiasm about its growing list of benefits (from longevity to diabetes and beyond) by keeping in mind its potential shortcomings, from bone loss to depression and now potentially immunological compromise.

While it’s unlikely that large swaths of the population will ever voluntarily restrict their caloric intake, it seems increasingly likely that CR mimetics will someday be a reality. Knowledge about the pitfalls of CR, and whether a given downside can be uncoupled from its benefits, will dramatically influence drug design, clinical indications for the use of mimetics, and strategies for long-term care of the end users.

Over at grailsearch.org, a partial list of aging-related pathologies. Imposing, all the more so for being incomplete. Stop on over and check the list — if you have suggestions for additions, I’m sure they’d like to hear them. For extra credit, store a copy in your wallet and read it aloud whenever someone talks about the “dignity” of the “natural process of aging.”

A meeting devoted to clinical research in aging. This is mainstream geriatrics, with a twist: the organizers have a higher-than-usual interest in work related to translating basic biogerontological findings into the clinic.

The UCSD Clinical Investigation Institute (CII) and Nature Medicine invite you to attend the third annual Frontiers of Clinical Investigation Symposium, Aging 2007: Bench to Bedside to be held October 18-20, 2007 in La Jolla, California. The theme for this year’s symposium explores innovative approaches to bridge laboratory investigation to clinical research in aging. The topic stands at the crossroads of many disciplines, including endocrinology and cardiology as well as neurodegenerative and musculoskeletal diseases. Multi-disciplinary sessions will include basic, translational, and clinical presentations on cutting edge research to provide an integrated approach to understanding the science of healthy aging. This symposium will provide unique insights and tools for optimizing and streamlining clinical investigation from discovery to drug development.

Abstract submission deadline is August 27th; registration gets costlier after September 16th.

More at the conference website.

(Hat tip to reader and biogerontologist John Cumbers for bringing this conference to our attention.)

The Journal of Pathology‘s most recent issue is devoted entirely to the pathology of aging. From the introductory article by Martin and Sheaff:

The rising numbers and proportion of aged individuals in the population is a global demographic trend. The diseases associated with ageing are becoming more prevalent, and the associated healthcare costs are having a significant economic impact in all countries. With these changes have come great advances in our understanding of the mechanisms of ageing. The mechanisms of cellular ageing at a genetic, protein and organelle level are becoming clearer, as are some of the more complex associations between environment and ageing. System ageing is also becoming better understood, and the potential biological advantages of ageing are being explored. Many of the advances in these fields are opening up the prospect of targeted therapeutic intervention for ageing and age related disease.

The articles cut a broad swath through the field, from molecular changes in aging cells to tissue- and system-scale phenomena in immunology, reproductive endocrinology, and beyond. The authors are in many cases the same eminences grises who would have written comparable reviews in high-impact basic science journals.

J Path itself is the highest-impact journal devoted to pathology, and its readership consist primarily of MDs and academic pathology researchers. The devotion of an entire issue to this subject is just the latest example of the increasing mainstream attention being paid to the biology of aging.

For your delectation, the table of contents:

While J Path doesn’t have a newsstand price, I must say I’d be tempted to pay it for this issue.