8.) Our current health care setting fails to prioritize such measures. What could be done to improve the situation? On the level of the individual person, health care professionals, health insurance providers, society and politics. How could we pay for this?

8/9

7.) In contrast for physiological, functional and anthropometric biomarkers, solid and broad human data exist! E.g. #VO2max, body composition (muscle and #fat mass/distribution), #muscle force and power, activity levels, gait speed and other frailty markers.

7/9

6.) How measure aging trajectories or "biological age"? Current state of molecular #biomarkers, e.g. #epigenetic marks, plasma proteomics or #telomere length.

6/9

5.) What does work? Interventions with solid data on human aging, #morbidity, #mortality and/or #longevity: physical activity, #sleep, #nutrition, #stress, social interactions, socioeconomic disparities, #climatechange and much more!

5/9

4.) Proposed "#anti-aging drugs" and interventions in human aging, e.g. #rapamycin, #metformin, #resveratrol, but also #reprogramming, #rejuvenation, #caloric restriction. Potentially negative effects on other health-beneficial interventions (e.g. #exercise).

4/9

2.) How to study aging? E.g. Genetic diseases of "accelerated aging" (e.g. #progeria), (super-) #centenarians and geography (e.g. in a so-called #BlueZone).

3.) How might human aging differ from that in animals? What could this mean for the study of model organisms in this field?

3/9

1.) What is aging? An inevitable normal biological process? A disease that can be treated or even cured? In any case, aging is one of the strongest risk factors for many (mostly chronic diseases), e.g. #cancer, #neurodegeneration and #dementia, or #cardiovascular pathologies.

2/9

This is opposed the therapeutic effect of PGC-1alpha in #Duchenne and other diseases, but similar to the worsening in other pathological models with elevated muscle glycogen ( #Pompe or Raptor KOs).

The project was supported by the Jain Foundation and @snsf-ch.bsky.social

doi.org/10.1101/gad....

Intriguingly, even though membrane integrity seems improved by #PGC-1alpha in dysferlin-deficient muscle, the overall pathology is worsened: potentially, the synergy in glycolytic shutdown and glycogen buildup contributes to this. BTW, PGC-1alpha needs dystrophin for full functionality!

3/4

Knockout of #dysferlin results in a.) increased glucose uptake, yet b.) strong downregulation of glycolysis, c.) elevated muscle glycogen levels, and d.) mitochondrial dysregulation and increased cGAS-STING activation in skeletal #muscle. This phenotype is improved by #exercise!

2/4

Our new paper on #metabolism in #dysferlinopathies / #LGMD2B is out! Why is restoration of membrane repair insufficient to improve disease pathology? Possible explanations in this paper by @regula-furrer.bsky.social and colleagues @biozentrum.unibas.ch @unibas.ch

doi.org/10.26508/lsa...

1/4 🧵

Just wondering who might have been fastest PI at today's @biozentrum.bsky.social staircase run???