SENS framework

Right, let's talk about the genuinely exciting work happening in rejuvenation biotechnology. The field's matured tremendously since I first proposed the SENS framework, and we're seeing multiple approaches that actually repair aging damage rather than merely slow its accumulation.

Senolytics are leading the charge - these drugs selectively kill senescent cells that accumulate with age and poison their neighbours through inflammatory secretions. The beauty is they target anti-apoptotic pathways that these zombie cells rely on for survival. We're seeing dramatic results in mice, and early human trials are showing reduced inflammation and senescent cell burden.

Senomorphics take a gentler approach - they modulate senescent cell behaviour without killing them, suppressing their toxic SASP secretions. Rapamycin and metformin fall into this category. Less side effects potentially, though I prefer the more decisive approach of elimination.

What's particularly fascinating is how senescence in immune cells drives aging throughout the body. DNA damage accumulates in immune cells, they become senescent, and this alone can trigger senescence and functional decline in multiple organs. It's a cascade effect - both through loss of immune surveillance and active SASP-mediated damage propagation.

The cellular mechanisms are multifaceted. We're dealing with DNA damage response pathways, p16/RB arrest mechanisms, oxidative stress cascades, and epigenetic dysregulation. In epithelial cells particularly, you get this early arrest driven by oxidative stress and defective DNA repair, creating both tumor-initiating and tumor-promoting conditions.

Here's the crucial bit though - we need combination approaches. That's why at LEV Foundation we're running RMR2 with eight different interventions targeting multiple damage categories simultaneously. No single intervention will get us to longevity escape velocity. We need the full toolkit: senolytics, stem cell therapies, mitochondrial interventions, partial reprogramming, the lot.

The translational challenges remain significant - we lack reliable biomarkers for senescent cell burden in humans, and we need careful dose selection and patient stratification. But the rapid progress from discovery to clinical testing is unprecedented. We're not just understanding aging anymore; we're actively dismantling it.