Spermidine improved cardiac measures and survival in separate mouse cohorts. Cardioprotection depended on cardiomyocyte Atg5 in a genetic experiment.
Spermidine improved cardiac measures and survival in separate mouse cohorts. Cardioprotection depended on cardiomyocyte Atg5 in a genetic experiment.
The Atg5 experiment used young mice with a severe autophagy defect, whereas the late-start survival experiment used older wild-type animals. That comparison supports cardiac mechanism involvement but does not assign the entire survival effect to cardiac autophagy.
An age-prediction measure and a validated surrogate for clinical benefit are different things. A change in a clock alone cannot establish that a person will live longer or remain healthier.
An age-prediction measure and a validated surrogate for clinical benefit are different things. A change in a clock alone cannot establish that a person will live longer or remain healthier.
Intervention studies should assess measurement reliability and links to meaningful outcomes alongside biomarker change.
Proofreading-deficient PolgA knock-in mice accumulated excess mitochondrial mutations and developed shortened lifespan and premature aging-like pathology. This demonstrates causality under an engineered high-mutation condition.
Proofreading-deficient PolgA knock-in mice accumulated excess mitochondrial mutations and developed shortened lifespan and premature aging-like pathology. This demonstrates causality under an engineered high-mutation condition.
Testing normal aging requires measuring naturally occurring mutation burdens and evaluating interventions started after damage has accumulated. The mutator experiment alone does not establish that late-life mutation reduction reverses aging.
The aged-muscle experiment combined p38 inhibition with soft-hydrogel culture and transplantation. It supports a localized cell-therapy research strategy.
The aged-muscle experiment combined p38 inhibition with soft-hydrogel culture and transplantation. It supports a localized cell-therapy research strategy.
It does not establish that systemic p38 inhibition alone rejuvenates aged muscle or is safe in humans.
In a randomized one-year study of 48 older adults, alagebrium had no independent vascular benefit and did not enhance exercise effects.
In a randomized one-year study of 48 older adults, alagebrium had no independent vascular benefit and did not enhance exercise effects.
A null result for this compound and cohort does not exclude every extracellular-matrix intervention. New candidates need compound-specific human evidence.
This is a real translational limitation. Animal experiments can identify mechanisms and candidates; they do not establish benefit or safe dosing in people.
This is a real translational limitation. Animal experiments can identify mechanisms and candidates; they do not establish benefit or safe dosing in people.
The research response is staged clinical testing with relevant health outcomes, rather than treating preclinical longevity as a clinical result.
Replacing part of old-mouse plasma with saline and albumin improved selected tissue outcomes without adding young plasma.
Replacing part of old-mouse plasma with saline and albumin improved selected tissue outcomes without adding young plasma.
The human component measured serum effects on cultured cells, not randomized clinical rejuvenation. Dilution and replacement mechanisms require separate testing.
Boredom so bad that suffering age-related decline & dying are preferred is unlikely:
Bored people don't typically commit suicide to escape boredom & suffering from age-related health decline cannot be understated. Retirees get bored, but anti-aging would allow good health for people to continue work (enabling more career building or changing careers), sports, dating, & other entertainment undiminished. Thus, aging therapies might reduce boredom.
Boredom so bad that suffering age-related decline & dying are preferred is unlikely:
Bored people don't typically commit suicide to escape boredom & suffering from age-related health decline cannot be understated. Retirees get bored, but anti-aging would allow good health for people to continue work (enabling more career building or changing careers), sports, dating, & other entertainment undiminished. Thus, aging therapies might reduce boredom.
More entertainment over time:
There are more entertainment options than ever & more created all the time. Games, music, video & written content are created faster than anyone can consume a tiny % of. Travel possibilities expand over time as travel becomes faster/easier & previously inaccessible places reachable.
The mouse aging atlas detects both altered gene expression within cell types and changing proportions of cells across organs. A bulk-tissue signal can combine these effects.
The mouse aging atlas detects both altered gene expression within cell types and changing proportions of cells across organs. A bulk-tissue signal can combine these effects.
Cell-resolved measurements and composition-aware analyses help distinguish mechanisms. A change in average expression alone does not prove that individual cells became younger.
Uncontrolled reprogramming carries real risks. The partial-reprogramming study used limited, cyclic factor expression to separate beneficial effects from adverse effects seen with stronger induction.
Uncontrolled reprogramming carries real risks. The partial-reprogramming study used limited, cyclic factor expression to separate beneficial effects from adverse effects seen with stronger induction.
Those mouse results motivate testing controllable and tissue-specific approaches; they do not establish universal safety or human rejuvenation.
Senescence has context-dependent functions. Experimental removal of senescent cells delayed wound healing in mice, illustrating why indiscriminate clearance cannot be assumed harmless.
Senescence has context-dependent functions. Experimental removal of senescent cells delayed wound healing in mice, illustrating why indiscriminate clearance cannot be assumed harmless.
Target selection, timing, tissue context, and safety outcomes need direct study; senolytic research does not require claiming that every senescent cell is detrimental.
In a two-strain mouse study, 20% calorie restriction improved survival in C57BL/6 females, while 40% restriction did not produce the same overall survival benefit relative to unrestricted feeding.
In a two-strain mouse study, 20% calorie restriction improved survival in C57BL/6 females, while 40% restriction did not produce the same overall survival benefit relative to unrestricted feeding.
Dose, genetic background and sex need to be tested together. Improvements in mitochondrial or proteostasis measures cannot substitute for measuring survival and functional health directly.
In a randomized trial of 60 postmenopausal women, dasatinib plus quercetin did not improve the primary 20-week bone-resorption endpoint in the overall group.
In a randomized trial of 60 postmenopausal women, dasatinib plus quercetin did not improve the primary 20-week bone-resorption endpoint in the overall group.
Signals in participants with higher senescent-cell burden justify further testing with prespecified selection criteria; they do not establish a general skeletal benefit.
Short-term ALK5 inhibition in old mice increased hippocampal progenitor measures and improved new muscle-fiber formation after experimental injury.
Short-term ALK5 inhibition in old mice increased hippocampal progenitor measures and improved new muscle-fiber formation after experimental injury.
Follow-up should measure durable tissue function and adverse effects, including cognition and uninjured muscle performance. Histological regeneration is a narrower result than those outcomes.
Condemning billions of others & waiting decades is the worst overthrow plan:
In ranking ways to overthrow a dictatorship, evaluation criteria should include how many others get hurt (collateral damage) & how quickly positive change happens. Globally withholding aging therapies kills billions of innocents & takes the ruler's remaining lifetime, and even then a positive result is far from assured as replacement dictators are common (eg, Venezuela). Almost any other plan is better.
Condemning billions of others & waiting decades is the worst overthrow plan:
In ranking ways to overthrow a dictatorship, evaluation criteria should include how many others get hurt (collateral damage) & how quickly positive change happens. Globally withholding aging therapies kills billions of innocents & takes the ruler's remaining lifetime, and even then a positive result is far from assured as replacement dictators are common (eg, Venezuela). Almost any other plan is better.
Number of autocracies & % of people living in them both decreasing:
Worldwide the trend is for fewer dictators and a smaller fraction of global population living under them, and not due to any decrease in natural lifespans of the dictators. Thus, this is already a decreasing problem.
Anti-aging's goal is less/no decrepitude & suffering, not more:
The existing healthcare (aka sick-care) system allows aging to cause widespread physiological decline, only treating individual diseases after clinical manifestation (mid-late stage of the full process),
and has caused longer end-of-life periods of frailty & decrepitude. Anti-aging's goal & so far its scientific reality is to reverse or prevent the initial stages of this decline to prevent decrepitude.
Anti-aging's goal is less/no decrepitude & suffering, not more:
The existing healthcare (aka sick-care) system allows aging to cause widespread physiological decline, only treating individual diseases after clinical manifestation (mid-late stage of the full process),
and has caused longer end-of-life periods of frailty & decrepitude. Anti-aging's goal & so far its scientific reality is to reverse or prevent the initial stages of this decline to prevent decrepitude.
A Mendelian-randomization study associated genetically longer telomeres with higher risk of several cancers and lower risk of selected non-neoplastic diseases.
A Mendelian-randomization study associated genetically longer telomeres with higher risk of several cancers and lower risk of selected non-neoplastic diseases.
Lifelong genetic proxies do not directly predict the effects of a short, tissue-specific treatment. Telomere interventions need disease-specific benefit and risk assessment.
Lower job turnover due to longer periods of health & productivity is good not bad:
To the extent that less aging allows people to stay in jobs longer than they otherwise would due to maintaining youth, and thus to not step aside for the more recently born, this is a net benefit to society. If chronologically younger competitors are more qualified, they should get a given job. If not, it is better for society for the job to be more competently done by the less recently born person.
Lower job turnover due to longer periods of health & productivity is good not bad:
To the extent that less aging allows people to stay in jobs longer than they otherwise would due to maintaining youth, and thus to not step aside for the more recently born, this is a net benefit to society. If chronologically younger competitors are more qualified, they should get a given job. If not, it is better for society for the job to be more competently done by the less recently born person.
New job types & some turnover will insure jobs for new generations:
Even if less aging results in less job turnover, turnover will happen as some decide to sabbatical or change careerrs and others are outcompeted despite their experience. Also, new job categories are created all the time, possibly at an accelerating rate.
Avoiding the health decline of biological aging does not preclude the benefits of living longer:
Living longer can bring benefits such as experience, knowledge, wisdom, & accomplishment, but these are not inherently tied to nor dependent on the poor health, suffering, disability, & death caused by age-related diseases
In fact, these benefits increase faster when young or middle aged. Untreated biological aging slows the accumulation of these benefits & eventually in many people reverses the process by robbing them of knowledge, wisdom, & skills.
Avoiding the health decline of biological aging does not preclude the benefits of living longer:
Living longer can bring benefits such as experience, knowledge, wisdom, & accomplishment, but these are not inherently tied to nor dependent on the poor health, suffering, disability, & death caused by age-related diseases
In fact, these benefits increase faster when young or middle aged. Untreated biological aging slows the accumulation of these benefits & eventually in many people reverses the process by robbing them of knowledge, wisdom, & skills.
Anti-aging therapies not likely to be expensive (for long):
Technologies, including medical technologies, and drugs get cheaper after introduction so won't stay expensive long. Many anti-aging therapies may be as cheap as existing medical treatments, just with different targets. Recent high therapy costs are due to treatments targeted at small patient groups, but development costs for aging therapies can be divided by everyone past middle age.
Anti-aging therapies not likely to be expensive (for long):
Technologies, including medical technologies, and drugs get cheaper after introduction so won't stay expensive long. Many anti-aging therapies may be as cheap as existing medical treatments, just with different targets. Recent high therapy costs are due to treatments targeted at small patient groups, but development costs for aging therapies can be divided by everyone past middle age.
Governments will subsidize treatments:
The aged currently cost governments huge amounts for medical costs & pensions. Even expensive anti-aging therapies would be cheaper for governments to subsidize directly than current standard of care that mostly keeps the old unhealthily.
Overpopulation unlikely to be caused by less/no aging:
Population growth is primarily determined by birth rates, not death rates. Birth rates are falling, so global population projected to stop growing (@~11B). Peak population primarily determined by how fast birth rates fall from well above 2 & birth rates drop as health improves so healthspan increases could even help. Only a small reduction in birth rate compensates for reduced age-related deaths.
Overpopulation unlikely to be caused by less/no aging:
Population growth is primarily determined by birth rates, not death rates. Birth rates are falling, so global population projected to stop growing (@~11B). Peak population primarily determined by how fast birth rates fall from well above 2 & birth rates drop as health improves so healthspan increases could even help. Only a small reduction in birth rate compensates for reduced age-related deaths.
Global supply of land/food/water/etc. more than sufficient:
Even if population grows, world population density is vastly lower than it could comfortably be. Global food supply is increasing faster than population & hunger expected to be eradicated worldwide by 2030. Population growth rate will be slow enough to allow for needed adaptations.
In mito-QC reporter mice, loss of Pink1 left basal mitophagy comparable in most examined tissues, with pancreatic islets an exception.
In mito-QC reporter mice, loss of Pink1 left basal mitophagy comparable in most examined tissues, with pancreatic islets an exception.
Direct tissue-level turnover measurements are needed alongside pathway markers. Basal and stress-induced mitochondrial clearance can use different mechanisms.
Human progress is not driven by urgency from impending death:
Many economic pressures drive individual incentives that in turn drive overall societal progress irrespective of lifespan: food & survival, competition at work & for mates, security, property, knowledge, entertainment, admiration. Few think that the doubling (tripling) of lifespans in the past century(ies) has slowed rate of progress & many (most?) think progress is faster now.
Human progress is not driven by urgency from impending death:
Many economic pressures drive individual incentives that in turn drive overall societal progress irrespective of lifespan: food & survival, competition at work & for mates, security, property, knowledge, entertainment, admiration. Few think that the doubling (tripling) of lifespans in the past century(ies) has slowed rate of progress & many (most?) think progress is faster now.
Wasting a resource one has in abundance is a sign of being better off:
To the extent to which progress is slowed because people waste more time as a result of having more, this is best seen as a sign of good times. One wastes what one has in abundance and having enough time to waste some is better than having too little.
Most hard data suggests the world is improving, not getting worse:
By most objective measures the world has been on a clear, positive trajectory, eg: lower global poverty & hunger, more recreation time, less violence & killing, improving education & health, faster travel & communication, increasing engineering & computational capabilities.
Most hard data suggests the world is improving, not getting worse:
By most objective measures the world has been on a clear, positive trajectory, eg: lower global poverty & hunger, more recreation time, less violence & killing, improving education & health, faster travel & communication, increasing engineering & computational capabilities.
Natural does not mean better:
Plenty natural is bad & much unnatural good, including modern healthcare (see appeal to nature fallacy). Anti-aging natural-ness is no more a problem than plumbing, vaccines, antibiotics, surgery...
Natural does not mean better:
Plenty natural is bad & much unnatural good, including modern healthcare (see appeal to nature fallacy). Anti-aging natural-ness is no more a problem than plumbing, vaccines, antibiotics, surgery...
Long lives or negligable aging are natural:
Some species live for 500 years, others appear not to age (no increasing risk of death w/ age), so evolution has created natural examples.
Those too old to be productive or healthy are a burden, but longer health is not:
Longer life without late-life improvements in productivity & health would cost more in pensions & healthcare, but less/no aging would make the currently projected unsustainability of western pension &
healthcare costs less problematic & may be the best way to avoid/minimize the projected demographic disaster (eg, bankruptcy of US Social Security). Increasing healthspans would improve economies
by improving the dependency ratio due to the shrinking fraction of life that is dependent.
Those too old to be productive or healthy are a burden, but longer health is not:
Longer life without late-life improvements in productivity & health would cost more in pensions & healthcare, but less/no aging would make the currently projected unsustainability of western pension &
healthcare costs less problematic & may be the best way to avoid/minimize the projected demographic disaster (eg, bankruptcy of US Social Security). Increasing healthspans would improve economies
by improving the dependency ratio due to the shrinking fraction of life that is dependent.