Latest Research About Reversing Aging Cells

Dr. Robins stated that the conventional advice of diet and exercise remains the most validated approach to reduce senescent cell burden. In mouse models, exercise and dietary restriction produce outcomes comparable to senolytics, though sometimes the drug provides a slightly greater benefit. He emphasized that not everyone will adopt these lifestyle habits, which justifies developing pharmaceutical options for those who don't. The research on specific dietary components (carb/protein/amino acid ratios) is ongoing and not yet prescriptive. His key advice was to adopt an exercise routine and eating pattern that fit your life, rather than attempting extreme diets that are unsustainable. He mentioned that he personally learned this only after turning 50 when age-related knee pain forced him to find appropriate exercise.

Dr. Robins and collaborators published the first study showing fisetin has senolytic activity, which led to multiple clinical trials. He himself began taking fisetin during the pandemic after mouse data showed protection against a SARS-CoV-2-like virus. He acknowledges that many longevity researchers self-experiment with fisetin, but stresses that the lack of dosing data is a problem. The field needs better biomarkers to identify who has high senescent cell burden and would benefit. He does not recommend large doses for everyone, noting that it's still experimental. His team is developing analogs with higher potency and better targeting, aiming for clinical trials.

Dr. Robins explains that rapamycin doesn't kill senescent cells but suppresses their inflammatory factor release. It's not fully known which hallmark of aging rapamycin primarily targets—whether it's inflammation, metabolism, or stem cell function. He cites a study by Joan Mannick showing that intermittent rapamycin treatment boosted immune responses to vaccines in older people. He also mentions rapalogs, which may more selectively inhibit the mTOR complex 1 associated with side effects. The optimal dosing and start age remain open questions, but rapamycin remains a cornerstone of pharmacological anti-aging research.

Dr. Robins mentioned metformin alongside SGLT2 inhibitors as drugs that normalize metabolism and reduce senescence markers. He noted that SGLT2 inhibitors also show broad healthspan benefits. He emphasized that these are already used by millions for type 2 diabetes, and the geroscience interest is their ability to improve health across multiple systems. He did not personally continue metformin but sees it as a promising agent if the TAME trial confirms efficacy. He also highlighted its affordability as key for equitable deployment.

At a recent aging research meeting in Copenhagen, a panel of pharma experts unanimously agreed that GLP-1 agonists may be the first genuine anti-aging drugs. Dr. Robins notes that every time he opens a journal, there's an article about a GLP-1 compound positively affecting an age-related disease. He highlights osteoarthritis: patients show structural improvements in the joint, not just pain relief from weight loss. Surprisingly, receptors for GLP-1 are expressed on chondrocytes in the joint and neurons in the brain, hinting at direct signalling beyond appetite. However, he cautions about potential adverse effects on muscle mass, and companies are developing combination drugs to preserve muscle function. The mechanism remains unclear, but the broad benefits have made GLP-1 agonists a hot topic in geroscience.

Dr. Robins' team has identified compounds that reduce senescence markers without inducing cell death, and observed that some drugs make senescent cells appear younger at the transcriptional and epigenetic levels. He calls partial rejuvenation the 'holy grail' because it could circumvent the problem of killing non-replenishable cells like neurons. They are now running assays to validate these effects, suspecting that many drugs thought to target individual hallmarks of aging actually work by partially rejuvenating aged cells. The approach uses multi-omics readouts—transcriptome, lipidome, metabolome—to confirm youth-like cellular states. This could lead to drug cocktails that make cells 'look younger' without the risks of gene therapy or full reprogramming.

Dr. Robins explains that in the liver alone, one can find senescent hepatocytes, senescent Kupffer cells, and senescent infiltrating immune cells, each with a different inflammatory signature. This implies that a disease like liver fibrosis might require clearing one subtype, while another liver disease might require clearing a different subtype. Similarly, in the brain, it appears that microglial cells develop a senescent-like phenotype, and clearing those may be beneficial, while clearing senescent neurons might be detrimental. However, animal data so far haven't shown adverse effects from clearing a few senescent cells, even in the brain. The field is still working on markers to distinguish 'good' acute senescent cells (wound healing, embryogenesis) from 'bad' chronic ones.

Dr. Robins describes how senescence can be triggered by oncogene activation, and the ensuing cell cycle arrest is an anti-tumor mechanism. However, the same pathways that block apoptosis in tumor cells also keep senescent cells alive. Thus, drugs targeting those survival pathways—like dasatinib, which inhibits tyrosine kinase receptors—kill both cancer cells and senescent cells. This conceptual overlap suggests that senolytics, by clearing cells with oncogene activation before they break through senescence arrest, may also reduce cancer risk. Many natural products with senolytic properties similarly show anti-cancer activity. This dual function positions senolytics as agents that simultaneously extend health span and potentially reduce cancer incidence.

Dr. Robins is part of a collaboration with Albert Einstein and Columbia University to sequence centenarian genomes. They discovered a more active variant of SIRT6 that led them to study fucoidin as a SIRT6 agonist. The vision is that one day, safe gene editing could introduce such variants into somatic cells. However, significant safety concerns remain: off-target effects, cost, and the fact that beneficial variants can counterbalance harmful ones (some centenarians carry APOE4 or BRCA1 mutations but still live long). He notes that current therapies should be developed for everyone, not just the wealthy, and gene editing will require much more validation before it's used in healthy people. Nevertheless, the lab has already shown that delivering a centenarian SIRT6 variant to mouse liver via AAV improves healthspan.