Advocate for and adopt a proactive medical approach focused on preventing diseases by targeting the biology of aging, rather than a reactive approach that treats diseases only after they occur.
Implement a parallel approach combining Medicine 2.0 (treating established diseases) with Medicine 3.0 (proactive interventions targeting aging biology), viewing them as complementary rather than mutually exclusive.
Advocate for reallocating a greater proportion of research dollars from disease-specific treatments to foundational biology of aging, as this proactive investment could reduce the overall burden of late-life diseases.
Understand that biological aging is the greatest risk factor for most major causes of death, highlighting the critical need for increased research funding in this area.
Reject the widespread belief that aging is an unchangeable process; recognize that it is malleable and can be influenced through scientific interventions.
Prioritize extending “healthspan” (the period of healthy life) rather than merely extending life in a frail state, which is the core goal of the aging field.
Dispel the misconception that one must choose between extending healthspan or lifespan, as evidence suggests they are linked and tend to improve together when targeting aging biology.
Refrain from labeling aging as a disease, as it is a risk factor for many diseases, and doing so can confuse scientific discussion and policy.
Define “health” in terms of your individual ability to perform desired activities, recognizing that personal goals (e.g., gardening vs. heli-skiing) shape what a healthy life means.
Engage in the “marginal decade” exercise by identifying the most important physical, cognitive, emotional, and social activities you wish to maintain in the last decade of your life. This helps guide personalized health planning.
Conduct economic modeling to quantify the vast societal benefits of geroprotective drugs, such as increased workforce participation, delayed Medicare eligibility, and reduced healthcare spending.
Emphasize public education about the critical role of prevention in age-related diseases like Alzheimer’s, especially given the limited effectiveness of current treatments despite massive spending.
Believe that defeating major age-related diseases like Alzheimer’s, cancer, and heart disease will ultimately come from understanding and targeting the biology of aging.
Recognize immune dysfunction as a critical factor contributing to poor health outcomes and mortality in older individuals, warranting proactive rejuvenation efforts.
Prioritize research and investment into understanding and proactively rejuvenating the immune system to combat age-related susceptibility to infections and other diseases.
Navigate the longevity field by seeking out scientific rigor and being aware of the “huge gray area” between real science and “snake oil.”
Prioritize understanding the “why” behind observed correlations, seeking clear mechanistic connections for interventions, especially those preserved in humans, to build confidence in their efficacy.
To advance understanding of complex biological processes, focus on designing specific experiments that can directly test causal relationships rather than relying solely on observational correlations.
Avoid oversimplifying complex biological processes; instead, delve into specific changes within cell types and their interactions to gain a deeper, more productive understanding.
Understand that age-related diseases are downstream effects of biological aging, and interventions slowing aging may not be effective once a disease’s pathology has diverged mechanistically from the underlying aging process.
Focus on developing “aging rate indicators” that can reliably and quickly show whether an intervention is slowing the aging process in youth, rather than just biomarkers that reflect accumulated age.
Understand the difference between biomarkers (something that changes with age) and aging rate indicators (something that tells you how fast you are aging), as the latter is crucial for clinical trials.
Focus on building robust evidence to establish confidence in human aging rate indicators, which is crucial for their acceptance by regulatory bodies like the FDA and their use in clinical trials.
Exercise critical judgment when reviewing observational studies on metformin’s effects, as some may contain methodological flaws that invalidate their conclusions regarding mortality benefits.
Always critically examine the experimental conditions and underlying causes of observed effects, as initial conclusions can be misleading if the baseline pathology is extreme and unrepresentative.
Critically re-evaluate long-standing scientific metaphors or hypotheses, such as the Hayflick limit and its relation to aging, to avoid blindly following historical assumptions.
Be cautious of oversimplified explanations for aging, such as the sole accumulation of senescent cells, as they can hinder productive scientific inquiry and lead to misleading conclusions.
Be cautious of scientific terminology that, while seemingly convenient, can “trap you into patterns of thought” that are nonproductive and misleading, preventing deeper investigation into complex biological details.
Promote a culture among scientific reviewers that values new ideas and approaches, rather than favoring incremental research or proposals that merely align with established frameworks.
Advocate for and engage in more discovery science and “thinking outside the box” in aging research, as over-reliance on the “hallmarks of aging” may have prematurely narrowed the field.
Pursue research into promising areas of aging biology even if they are not explicitly listed as “hallmarks of aging,” as the current list may be incomplete and prematurely narrow the field.
Leverage the “hallmarks of aging” as a useful conceptual tool for communicating the idea of biological aging and its mechanistic basis, but avoid treating them as an exhaustive or dogmatic list.
Approach the “hallmarks of aging” framework with critical thinking, recognizing that its widespread acceptance may sometimes hinder deeper mechanistic investigation and narrow the scope of research.
Understand that significant research related to aging, such as studies on senescence in cancer or Alzheimer’s, is being conducted across various NIH institutes, even if not explicitly categorized as “aging research.”
Explore strategies to reallocate existing disease-specific research funds (e.g., NCI funding for cancer) towards investigating disease prevention through geroprotection, to overcome “turf war” issues.
Support increased funding for foundational aging science by advocating to policymakers, as current lobbying efforts for aging research are significantly underrepresented compared to disease-specific groups.
Despite historical underfunding and resistance, maintain optimism that the landscape for biological aging research funding and public support is beginning to shift positively.
Recognize that the reactive approach to disease is deeply ingrained in pharmaceutical, biomedical, and basic science research, and efforts are needed to shift this fundamental mindset.
Move beyond the binary medical definition of healthspan (free of disability/disease) to an analog, more nuanced understanding that allows for continuous discussion and measurement of health quality.
Utilize the concept of “healthspan” as a clear and useful term to communicate the goal of increasing the healthy period of life to a broader audience.
Understand that “biological age” is not a single number but rather a composite of the ages of individual organs and systems (e.g., heart, liver, brain), reflecting overall health.
When considering biological age tests, question whether their results are more predictive of future years of life than chronological age, which currently remains the single best predictor.
Consider the adoption of biological age clocks by life insurance companies for their actuarial algorithms as a strong indicator of their validity and practical utility.
Stay informed about the development of epigenetic algorithms, as they hold potential to eventually replace or complement many traditional biomarkers in measuring biological age.
Investigate and support the development of technologies for targeted epigenetic modifications, as they hold potential to modulate specific aspects of biological aging.
Explore the dozen or so identified aging rate indicators (e.g., changes in macrophage types, UCP-1 levels) that consistently change in slow-aging mice across various interventions, as these may translate to humans.
Recognize the value of comprehensive health evaluations in humans, as they can provide a rich understanding of health status that is often underestimated by animal researchers.
Be aware that most interventions effective in mouse models do not directly translate to humans due to species differences, side effects, and other factors, necessitating careful human clinical trials.
Maintain cautious optimism that interventions and biomarkers targeting normative biological aging (as opposed to artificial disease models) are more likely to translate successfully from mice to humans.
Appreciate the role of rodent-based research as a critical first step in drug development, even if it doesn’t guarantee human efficacy, as most successful human drugs have a foundation in such studies.
Consider testing potential aging rate indicators in human cohorts with extreme differences in health behaviors (e.g., obese smokers vs. healthy exercisers) to identify signals of slowed aging, while acknowledging limitations regarding sensitivity.
Investigate epigenetic algorithms like Dunedin-Pace, which show correlations with mortality and healthspan metrics, as potential tools for assessing biological aging.
Learn from long-lived animal models (e.g., tiny dog breeds) where aging is slowed across multiple systems (cancer, neurodegenerative, digestive, joint diseases), indicating a broad impact on the aging process.
Emphasize exercise for its profound impact on quality of life and healthspan, even if its direct effect on lifespan is perceived as small, as the improved quality justifies the effort.
Explore the molecular changes induced by exercise, such as increased GPLD1 (beneficial for brain neurogenesis) and Iresin (beneficial for fat), as these are also elevated in slow-aging mice.
Investigate the shared molecular pathways and effects between anti-aging drugs and exercise, as some anti-aging drugs in mice show similar beneficial molecular changes to those induced by exercise.
For animal studies, favor drug formulations that allow for easy administration (e.g., mixed into food or water) over laborious methods like injections, to streamline research efforts.
Despite skepticism and methodological concerns in some studies, consider investigating metformin’s potential geroprotective effects due to consistent observational data suggesting reductions in dementia, cancer, and cardiovascular disease.
Recognize that metformin likely reduces biological aging in the context of diabetes by effectively managing diabetic symptoms, but its efficacy in non-diabetic individuals for anti-aging purposes is less clear.
Investigate and understand the cell-specific mechanisms of action for drugs like metformin (e.g., concentration in liver and gut, but not muscle) to better predict their effects and potential side effects.
Shift research focus from broad “body-wide” drug effects to detailed organ-specific and tissue-specific changes, and how these interact, to better understand mechanisms and target therapies.
Recognize that while mechanistic understanding is valuable, it’s sometimes necessary to pursue promising therapies with suggestive evidence and low side effects, even before fully elucidating every cellular mechanism.
For off-label use of rapamycin for healthspan, a common practice among prescribing doctors is once-weekly dosing in the 3-10 milligram range, based on current understanding of side effects and efficacy.
Recognize that intermittent rapamycin dosing (e.g., once weekly) is hypothesized to reduce side effects by allowing trough levels to bottom out, thereby minimizing off-target effects on mTOR complex 2.
Understand that daily rapamycin dosing may be associated with a higher likelihood of side effects like bacterial infections or mouth sores, while once-weekly dosing has shown side effect profiles similar to placebo in some trials.
Do not take resveratrol for longevity or anti-aging purposes, as there is no compelling scientific evidence to support its efficacy, despite its continued marketing and public interest.
Recognize that it takes a long time to dispel widely accepted but unproven health claims (like resveratrol’s benefits), especially when there’s a profit motive, requiring patience and persistent communication of evidence.
Approach NAD boosters (NR, NMN) with skepticism regarding their longevity benefits, as current evidence, including strong negative findings from the ITP, is not compelling despite conceptual plausibility.
Understand that while NAD is a crucial molecule and its decline with age is plausible, the scientific data on whether boosting NAD through precursors increases lifespan or improves healthspan is “decidedly mixed.”
Be critical of expensive oral NAD precursors (NMN, NR), as data suggests they may break down to niacin in the gut, raising questions about their unique benefits over cheaper alternatives.
Weigh the potential risks of NAD boosters, such as kidney inflammation and pathology observed in aged mice at high doses, and exercise caution, particularly when considering their use in companion animals.
Support detailed investigation into the potential benefits of parabiosis or plasma exchange in humans, as its efficacy could be a “game changer” given the existing medical infrastructure for transfusions.
Focus scientific efforts on identifying the specific beneficial molecules or cells in young blood and detrimental factors in old blood, rather than relying on complex, non-specific interventions like parabiosis.
Anticipate that any benefits from blood-based rejuvenation strategies (like parabiosis) will likely stem from a complex combination of factors, rather than a single molecule, given the difficulty in identifying simple mechanisms.
Explore therapeutic plasma exchange (replacing old plasma with albumin) as a logistically simpler starting point for clinical trials investigating blood-based rejuvenation, despite its limitations in testing the “young blood” hypothesis.
When evaluating parabiosis research, consider that the surgical procedure itself can shorten lifespan in rodents, and benefits observed might be influenced by these procedural impacts.
Recognize that cells exhibiting characteristics of senescence accumulate with age in various tissues, and their removal has shown some health benefits in animal models, warranting further investigation.
Acknowledge that there is some evidence suggesting that the removal of P16 positive senescent cells can lead to improvements in health and longevity, despite ongoing debate and challenges in replication.
Be mindful of the precise use of the term “senescence,” as its current association with specific cell types (senescent cells) has “stolen” its broader meaning of aging, leading to confusion.
Consider the potential of anti-aging drugs to prevent age-related diseases like cancer, as evidenced by their ability to postpone cancer and reduce incidence rates in mice.
Exercise caution regarding products marketed for longevity that lack scientific evidence or rigorous testing, as many are sold to “gullible customers” without proven efficacy.
Do not rely on direct-to-consumer biological age tests for clinical practice or actionable recommendations due to unknown precision, accuracy, and the current “complete mess” of the industry.
Approach claims of a single “biological age” number with skepticism, as it oversimplifies a complex dataset of individual health metrics into a potentially unhelpful value.
Employ biomarkers as easily measurable indicators to gain objective information about hard-to-measure biological states or behaviors, such as cotinine levels for smoking.
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