Dr.  Ron  Rosedale.  Too  Much  Protein  –  Effects  on  Longevity  Aging  and  Cancer    

Since  I  have  a  half  an  hour  to  discuss  nutri3on,  cancer  and  aging,  

I  will  not  waste  3me.  

And  in  fact  I'll  have  to  even  do  more.  

It's  said  that  the  only  real  way  to  learn  

it's  first  to  unlearn  things  that  you  think  you  know.  

And  that  always  seems  to  entail  confusion.  

So  I  will  not  consider  my  job  a  success  tonight,  this  a@ernoon,  

unless  I  have  confused  you.  

So  remember  that  at  the  end.  

Here's  the  answer.  

It's  really  all  you  have  to  now.  

This  is  what  I've  said  for  many  years,  actually  several  decades.  

And  if  I'd  have  to  summarize  everything  in  one  sentence  it's  this...  

That  your  health  and  lifespan  will  most  be  determined  

by  the  propor3on  of  fat  versus  sugar  you  burn  over  a  life3me.  

You  can  gauge  anything  you  hear  about  nutri3on  with  that  statement.  

If  it  helps  you  burn  fat,  it's  probably  good.  

If  it  doesn't,  it's  probably  not.  

And  that  will  be  determined  by  the  communica3on  of  hormones.  

And  those  hormones  will  be  determined  by  what  you  eat.  

It's  not  the  simple  "calories  in,  calories  out".  

You  eat  to  affect  the  hormones  

that  will  affect  whether  you  burn  sugar  or  whether  you  burn  fat.  

In  other  words  every  meal  you  eat,  it's  probably  the  most  important  effector  

of  hormones  that  you  will  be  exposed  to  that  day.  

And  that  hour  and  a  minute.  

Now  25  years  ago  there  were  a  handful  or  less  of  people  

who  were  recommending  low  carbohydrate.  

And  the  impetus  for  that  really  was  to  lose  weight.  

And  it  was  found  that  a  low  carbohydrate  diet  was  very  good  for  weight  loss.  

The  other  handful  of  people,  other  than  myself,  

were,  as  I  say,  looking  to  lose  weight,  or  looking  to  affect  weight  loss  

and  a  high-­‐protein  diet  worked  very  well,  

plus  fat  was  really  vilified  at  that  3me  and  it's  s3ll  vilified.  

But  if  you  can  imagine  a  quarter  of  a  century  ago,  

fat  was  the  Darth  Vader  of  health.  

And  so  nobody  would  even  aQempt  to  think  of  ea3ng  a  high-­‐fat  diet.  

Except  me.  

Because  I  was  not  dealing  with  weight  loss,  I  didn't  really  care  at  all  about  weight  loss.  

I  wanted  to  treat  diabe3cs  and  heart  disease  pa3ents.  

And  I  knew  that  protein  was  very  good  at  turning  into  sugar  

and  the  diabe3cs'  one  of  the  major  problems  was  gluconeogenesis,  

where  they  turned  protein  into  sugar,  

so  I  could  not  see  the  point  of  feeding  a  diabe3c  a  lot  of  protein  

and  certainly  I  didn't  see  the  point  of  feeding  a  diabe3c  sugar  

and  then  giving  them  medica3ons  to  get  rid  of  that  sugar.  

That  made  no  sense  whatsoever.  

Which  is  s3ll  being  done.  

So  what's  le@?  

I  mean  there's  not  a  whole  lot  of  choices  here.  Right?  

So  I  went  into  a  high-­‐fat  diet.  

And  worked  very  well  for  diabetes,  cardiovascular  disease...  

And  diabetes  in  my  studies,  and  my  background  was  the  biology  of  aging,  

was  really  a  model  for  accelera3ng  aging.  

So  I  knew  I  was  onto  something.  

And  the  only  thing  that  I  think  I've  changed  over  the  years  

has  been  just  how  important  it  is  to  restrict  protein.  

In  the  book  that  I  put  out  maybe  a  decade  ago,  a  liQle  over,  

the  only  nutrient  I  had  people  count  was  protein.  

So  I  knew  it  was  important,  but  I  would  have  to  say  that  today  

I  would  say  it  perhaps  is  more  important  to  restrict  protein  

than  it  is  to  restrict  carbohydrates.  

And  I  know  that's  a  new  statement.  

But  I  told  you  I  wanted  to  confuse  you  a  liQle  bit.  

And  I  will  hopefully  be  able  to  give  a  few  reasons  why  in  the  next  20  minutes  or  so.  

But  to  do  so  we  have  to  go  back  pre-­‐Paleo.  

And  Paleo  was  at  maybe  half  a  billion  years  of  something...  

When  did  Paleo  start?  Not  even  then,  right?  

Few  hundred  million...  

Well,  life  started  about  4  billion  years  ago.  

And  that's  really  when  the  rules  of  ea3ng  began.  

Actually  before  that,  but  we  won't  go  there.  

So  let's  quickly  take  an  overview  of  life.  

We  started  out  as  single  cell  organisms  floa3ng  around  the  oceans.  

Lots  of  them.  

Unicellular  organisms  whose  requisite  to  stay  alive  was  to  divide.  

Divide  as  fast  as  you  can  and  beat  your  neighbors  to  the  punch.  

What  does  that  sound  like  today?  

Cancer  -­‐  okay,  that's  the  history  of  cancer.  

It's  our  bacterial  heritage.  

Unicellular  organisms  were  dividing  and  that  went  on  by  the  way  

for  a  billion  and  a  half,  maybe  two  billion  years...  

Half  of  our  en3re  life3me.  

The  history  of  life  was  single  cell  organisms  flourishing  in  the  oceans.  

Un3l  one  of  them  developed  photosynthesis  

and  started  pu^ng  out  oxygen  into  the  atmosphere.  

Well,  that  killed  about  everything.  

There  were  no  defenses,  we  talk  about  oxida3on.  

That  was  the  major  pollu3on  crisis  for  life.  

It's  es3mated  that  at  least  90%  of  all  life  was  wiped  out.  

Un3l  one  smart  bacteria  figured  out  a  way  to  use  that  oxygen...  

...and  burn  organic  material  food  with  it.  

Which  did  wonderful  things  because  it  saved  the  organisms  from  being  oxidized  

and  generated  tons  of  energy.  

And  then  another  unicellular  bacterial  en3ty,  organism,  

ate  that  proto-­‐mitochondria,  that  we  call  mitochondria  now  

and  they  became  friends.  

Were  that  proto-­‐mitochondria  got  nice  room  and  board  

in  exchange  for  lots  of  energy.  

So  then  you  had  eukaryotes.  

And  you  had  the  ability  then  to  fuel  mul3cellular  organisms.  

Mul3cellular  organisms  have  a  lot  more  genes.  

Not  necessarily  you  need  an  individual  cell,  

but  you  have  a  lot  of  cells  with  a  lot  of  genes.  

And  they  have  to  mul3ply  -­‐  it  took  a  lot  of  energy.  

That  couldn't  have  occurred  

un3l  you  had  that  nice  symbio3c  rela3onship  

between  one  bacteria  and  a  proto-­‐bacteria  and  a  lot  of  energy  informed  

and  protec3on  from  oxidizing.  

So  it  was  a  great  liQle  symbiosis,  

probably  the  greatest  event  in  the  evolu3on  of  life.  

Because  that  allowed  for  everything  else,  

culmina3ng  maybe,  if  you  want  to  call  us  a  combina3on...  us.  

So  is  allowed  mul3-­‐cellularity  and  a  division  of  labor.  

The  greatest  division  of  labor  

came  between  the  genome,  our  genes,  the  informa3on  of  life  

and  the  other  cells  around  it.  

The  other  cells  around  it,  called  the  soma  -­‐  its  purpose  is  to  protect  that  genome  

and  pass  it  along.  

That's  the  purpose  of  the  division  of  labor  

between  the  genome  and  soma.  

Huge  dis3nc3on  and  a  huge  event  in  the  history  of  life.  

Why?  

Because  that  is  why  we  die.  

There  was  no  death  un3l  then.  

And  the  purpose  of  that  soma  is  to  protect  that  genome,  pass  it  along  

and  then  nature  doesn't  care.  

Which  is  why  we  die.  

Nature  doesn't  care  we're  going  to  die.  

It  takes  a  lot  of  effort  to  stay  alive.  

Now  that  tells  us  something  that  a  lot  of  people  don't  realize.  

And  this  isn't  going  to  be  a  very  popular  thing  to  say  here.  

However  it  tells  us  that  we  can  study  Paleo  all  we  want.  

And  we  can  argue  and  debate  what  Paleo-­‐man  ate.  

I  will  tell  you  they  won't  tell  us  much.  

If  we  finally  figure  it  out,  all  it  would  tell  you  is  what  diet  did  we  evolve  with  

that  might  have  maximized  our  reproduc3ve  success.  

Not  what  will  give  us  a  long  post  reproduc3ve  lifespan  

that  nature  doesn't  care  about,  

nor  is  there  a  way,  even  if  there  was,  

something  like  a  longevity  gene,  

it  would  be  no  way  to  pass  it  along.  

Since  the  power  of  selec3on  wins  quite  rapidly,  post  reproduc3vely.  

So  we  can  use  nature  in  general  

to  tell  us  how  to  live  a  long,  happy,  healthy  life.  

Because  nature  doesn't  care.  

We  are  probably  the  only  species  certainly  on  earth  that's  ever  even  thought  about  it.  

Nature's  purpose  is  to  get  those  genes  passed  along.  

But  that  also  created  a  problem  with  the  alloca3on  of  energy.  

As  the  mul3cellular  organisms  flourished  in  the  ocean,  

there  was  compe33on  and  an  arms  race,  especially  for  food.  

It  wasn't  so  plen3ful  anymore,  they  had  to  compete.  

But  that  also  meant  you  had  to  use  it  wisely  

and  you  had  to  decide,  

"Do  we  have  enough  food  to  replicate,  to  reproduce?  

Or  do  we  direct  our  resources  to  staying  alive?"  

That's  what  nature  cares  about.  

Nature  will  keep  us  alive  long  enough,  

such  as  we  have  a  sufficient  opportunity  to  pass  our  genome  along.  

Nature  has  a  lot  of  tricks  to  do  that.  

It  will  up  regulate  DNA  repair,  

heat  shock  proteins,  intercellular  an3oxidants...  

All  sorts  of  cool  stuff  that  nature  has  that  will  keep  us  alive  

so  that  we  can  pass  our  gene3c  informa3on  to  the  next  genera3on.  

All  we  want  to  do  is  to  apply  that  science  post  reproduc3vely.  

In  other  words  what  does  nature  do  that  allows  us  to  be  healthy  

such  that  we  can  take  care  of  our  genome  and  pass  it  along,  

so  that  we  can  use  that  knowledge  and  con3nue  using  it  post  reproduc3vely.  

Has  nothing  to  do  with  Paleo.  

So  that's  the  why  we  age.  

Mostly  because  nature  doesn't  care  that  we  do.  

The  how  we  age  is  a  liQle  bit  of  a  different  story.  

You  can  consider  aging  to  be  a  compe33on  between  damage  and  repair  of  damage.  

If  we  could  repair  damage  as  fast  as  it  occurred,  we  would  live  forever.  

However,  our  repair  mechanisms  become  damaged  too  over3me.  

And  that's  why  we  don't.  

And  we  can't  stop  that  damage.  

Now  there  are  different  reasons  why  we  can  stop  that  damage.  

One  being  we  can't  stop  breathing.  

And  so  you  hear  about  an3oxidants...  

Well,  your  best  an3oxidant  would  be  to  not  breathe.  

But  wouldn't  get  you  very  far.  

And  we  glycate.  

Glucose  combines  with  proteins  and  DNA  and  gums  up  the  works...  

You  know,  the  food  industry  is  called  carameliza3on.  

Oxida3on  is  called  rancidity.  

So  we  turn  rancid  and  we  caramelize  with  age.  

That's  "the  how".  

But  because  we  had  to  allocate  energy  towards  either  repairing  damage  

and  repairing  damage  is  really  where  it's  at...  

We're  not  going  to  stop  damage.  

We're  much  beQer  off  at  up  regula3ng  repair  of  damage.  

We  know  that  we  can  do  that.  

We  can  do  that  because  all  life  apparently  has  mechanisms  

to  allow  our  cells  or  single  cells  

to  outlast  a  nutrient  depriva3on  -­‐  A  famine.  

So  some  organisms  will  go  into  a  deep  freeze,  

some  will  desiccate  and  then  come  back  to  life  

at  a  future  more  opportunity  nutri3onally  advantageous  3me.  

Because  of  this  compe33on  for  food,  

the  choice  between  whether  we  should  allocate  our  resources  

towards  maintenance  and  repair,  i.e.  living  longer,  

or  inves3ng  those  resources  into  replica3on  or  reproduc3on.  

There  had  to  be  nutrient  sensors,  

there  had  to  be  something  that  says,  "How  much  food  is  there  available  to  do  this?"  

And  because  this  is  so  important  there  are  lots  of  them.  

We've  got  insulin  we  know,  IGF...  

And  they  are  close  cousins.  

In  fact  they  are  one  and  the  same  in  the  early  organisms  -­‐  worms.  

There's  no  such  thing  as  a  dis3nc3on  between  the  two,  

they  are  just  called  IIF.  

Insulin  IGF,  one  and  the  same.  

And  that's  one,  lep3n...  You've  got  energy  itself.  

The  ADP  to  ATP  ra3o,  NAD  to  NADH  ra3o,  

AMPK  which  is  the  enzyme  involved  in  changing  AMP  to  ATP.  

You  have  all  these  nutrient  sensors,  but  to  keep  yourself  from  becoming  schizophrenic,  

there  had  to  be  something  that  organizes  all  of  these.  

And  indeed  there  is.  

And  it's  called  the  mammalian  target  of  rapamycin.  

Most  people  haven't  heard  of  it.  

The  most  important  pathway  in  your  body.  

It  will  sense  all  the  nutrient  sensors  and  decide  should  this  self  replicate  

or  should  it  stay  alive  and  replicate  at  a  future  more  opportune  3me.  

That's  what  we  want.  

TOR,  the  target  of  rapamycin  has  been  around  since  the  beginning  of  animal  life.  

It's  found  in  bacteria,  it  way  predates  insulin...  

It  started  almost  with  life,  because  that  was  such  a  cri3cal  decision.  

Calorie  restric3on.  

We  know  that  that's  a  mechanism  that's  been  used  since  1930  to  extend  lifespan.  

It  slows  aging,  extends  life.  

How?  

Well,  a  friend  of  mine  actually  received  the  first  Methuselah  prize,  

which  is  given  to  the  aging  researcher  that  is  able  

to  keep  double  a  mouse's  lifespan,  from  two  to  four  years,  

by  inhibi3ng  IGF  receptors.  

So  if  you  inhibit  the  growth  of  a  mouse,  it  lives  longer.  

In  other  words,  if  you  inhibit  IGF,  

there  is  a  dichotomy  apparently  between  growth  reproduc3on  and  longevity.  

That's  what  this  slide  shows.  

The  role  of  insulin  and  IGF.  

Insulin  and  IGF  represent  a  family  of  hormones,  

growth  factors  that  regulate  metabolism,  growth,  

cell  differen3a3on  and  survival  of  most  3ssues  in  mammals  -­‐  that's  us.  

Insulin  and  IGF  ini3ate  their  ac3on  by  highly  homologous  signaling  systems.  

I  le@  that  in  there  because  a  lot  of  what  we  thought  

had  to  do  with  insulin  signaling  and  extending  lifespan  

wasn't  really  insulin,  but  IGF.  

They  cross-­‐react.  

High  insulin  is  bad  and  I  talked  about  this  20  years  ago,  

about  the  detriments  of  insulin  and  health,  

and  s3ll  believe  it.  

But  the  reason  high  insulin  is  so  bad  is  because  it  also  s3mulates  IGF  receptors.  

It's  a  growth  hormone.  

You  also  then  become  insulin  resistant,  but  that  insulin  resistance  by  the  way  

is  more  of  the  metabolic  aspects  you  become  insulin  resistant,  

but  not  the  anabolic  aspect.  

So  the  anabolic  aspect  of  high  insulin  flourishes.  

Well,  the  insulin  resistance  cells  are  actually  protected  from  the  glyca3on.  

I  talked  this  in  there  too,  again  in  this  ar3cle  as  a  quote.  

"Some  of  the  common  and  consistent  effects  of  calorie  restric3on  

in  rodents  and  nonhuman  primates  include  lower  fat  mass,  par3cularly  visceral  fat,  

"lower  circula3ng  insulin  and  IGF  concentra3ons  increase  insulin  sensi3vity,  

"lower  body  temperature,  lower  fat-­‐free  mass,  

decreased  levels  of  thyroid  hormones  and  decrease  oxida3ve  stress."  

So  when  people  see  that  their  thyroid  hormones  are  going  down  a  liQle  bit,  

when  they  follow  a  so-­‐called  ketogenic  high-­‐fat  diet  

and  they're  worried  about  and  you  hear  these  blogs  that  say,  

"You've  got  thyroid  disease."  

Not  in  the  least  -­‐  there's  a  very  healthy  way  to  live.  

You're  running  cooler,  

you're  alloca3ng  more  resources  towards  maintenance  and  repair  and  longevity.  

It's  not  thyroid  disease  and  I  know  that,  

because  your  TSH  does  not  go  up,  

which  is  how  you  actually  define  hyperthyroidism  in  medicine.  

So  don't  believe  all  that  stuff.  

"In  conclusion,  strong  similari3es  exist  between  insulin  IGF  

in  yeast,  worms,  flies,  mammals  and  humans."  

"...  Suggest  that  insulin  and  IGF  arose  early  in  evolu3on  

"and  is  a  central  component  of  an  an3-­‐aging  system,  

which  is  conserved  from  yeast  to  humans."  

In  other  words  it's  important.  

Does  it  apply  to  people?  

This  is  a  family  of  people  in  Ecuador  that  has  a  very  rare  disorder  

known  as  Laron  syndrome.  

They  basically  have  exactly  what  the  mice  have.  

Mice  that  lived  twice  as  long.  

They  have  an  IGF  recep3ve  muta3on,  

cancer  and  diabetes  is  unknown  despite  them  being  fat.  

Now  they  have  a  very  hard  life,  

they  died  a  lot  of  alcoholism  and  accidents.  

But  if  one  controls  for  those,  they  also  live  lots  longer.  

So  if  you  control  for  kind  of  non-­‐age  related  diseases,  

they  have  a  very  long  lifespan.  

"In  yeast,  worms  and  mice  the  restric3ng  growth  hormone  

"could  make  those  creatures  live  longer.  

Guevara-­‐Aguire-­‐-­‐  if  I'm  pronouncing  that  correctly...  

He  is  the  one  who  kind  of  discovered  this  Ecuadorian  family.  

It's  a  rare  syndrome  caused  by  a  gene  muta3on.  

Over  the  course  of  his  years  with  the  family  members  

he  no3ced  the  people  with  Laron  syndrome  almost  completely  avoided  cancer  and  diabetes.  

An  observa3on  that  squared  with  the  research  of  Longo  and  others  

who  have  done  this  in  yeast  and  animals.  

It  could  be,  because  cells  must  invest  energy  

in  either  trying  to  grow  and  reproduce  or  in  protec3on.  

I.e.  maintenance  repair,  what  I've  been  saying.  

It's  a  huge  decision  and  we  want  to  swing  it  towards  maintenance  repair.  

When  we  talk  about  cellular  replica3on,  we  want  to  curtail  that  for  the  most  part.  

Right?  

Because  then  you  curtail  cancer.  

In  nature  dwarf  models  live  longer.  

Ponies  live  longer  than  horses,  small  dogs  live  longer  than  large  dogs.  

It's  a  very  fascina3ng  field,  a  fascina3ng  field  in  aging.  

Un-­‐growth  hormone  increases  longevity.  

It's  a  drug  that  counters  growth  hormone  

and  it  inhibited  several  human  cancers,  

including  prostate,  brain,  breast  and  lung  cancers.  

Long-­‐term  effects  of  calorie  or  protein  restric3on  

on  serum  IGF  and  IGF  binding  protein.  

Our  data  provide  evidence  that  protein  intake  

is  a  key  determinant  of  circula3ng  IGF-­‐1  levels  in  humans.  

And  suggest  that  reducing  protein  intake  may  become  an  important  component  

of  an  an3-­‐cancer  and  an3-­‐aging  dietary  interven3on.  

There  is  a  huge  difference  between  a  low  carbohydrate  high-­‐protein  diet  

and  a  low  carbohydrate  high-­‐fat  diet.  

Namely  one  is  healthy  and  one  isn't.  

And  so  early  on  when  the  few  people  20  or  25  years  ago  

who  were  advoca3ng  low-­‐carb-­‐-­‐  

That  was  a  kind  of  a  revela3on,  it  was  good  enough,  

but  the  dis3nc3on  wasn't  made  between  high-­‐protein  or  high-­‐fat  par3cularly.  

And  virtually  everyone  else  went  to  high-­‐protein,  because  fat  was  so  vilified.  

And  that  really  set  it  back,  

because  there  were  a  lot  of  problems  with  high-­‐protein.  

And  it  worked  certainly  for  weight  loss.  

And  so,  the  advantageous  publicity  was  more  for  weight  loss,  

not  as  much  for  disease  and  diabetes.  

And  certainly  not  for  cancer.  

But  you  didn't  find  that  out  for  years.  

But  now  we  know.  

An  an3-­‐Atkins  low-­‐protein  diet  extends  lifespan  in  flies.  

Now  Atkins,  bless  his  soul,  at  least  got  low  carbohydrate  known...  

His  deal  was  just  low  carbohydrate  and  preQy  much  anything  else  went  

and  since  nobody  wanted  to  eat  fat  back  then,  

they  all  gravitated  to  high-­‐protein,  that  was  the  problem.  

It  appears  that  high-­‐protein  accelerates  aging,  reducing  protein  extends  life.  

Why?  

We  talked  about  insulin  and  IGF  

and  all  these  different  things  that  can  extend  life  and  affect  health  and  longevity  

and  they  all  intersect  at  the  mammalian  target  of  rapamycin.  

Rapamycin  is  an  an3fungal  agent.  

It  was  discovered  in  the  eastern  island  of  Rapa,  so  they  called  it  rapamycin.  

And  they  found  it,  well,  inhibits  cancer.  

So  it's  an  immunosuppressant.  

And  it's  used  to  this  day  as  an  immunosuppressant  for  organ  transplanta3ons,  

especially  kidney  transplanta3ons.  

So  people  take  rapamycin  which  inhibits  mTOR.  

They  found  that  those  kidney  transplanta3on  pa3ents  who  were  taking  rapamycin  

ended  up  having  a  far  lower  incidence  of  cancer.  

Lo  and  behold.  

Even  though  it  inhibited  immunity.  

In  other  words  it  was  something  else  there  

that  was  really  working  wonders  as  far  as  cancer.  

Okay,  so  this  is  what  you  will  be  quizzed  on.  

Now,  the  amino  acids  affect  TOR  directly.  

No  middleman.  

Doesn't  have  to  affect  hormones,  it  doesn't  have  to  raise  insulin  or  IGF.  

It  just  goes  right  to  mTOR,  does  not  pass  go.  

You've  got  insulin  and  IGF,  so  you've  got  growth  factors.  

See  that  at  the  very  top?  

All  the  growth  factors  up  regulate  TOR.  

You've  got  glucose  -­‐  again,  directly  it  will  affect  increase  insulin  

but  all  by  itself  it  increases  TOR.  

Here  is  TOR,  it's  actually  in  two  complexes  -­‐  TORC1,  TORC2.  

They  do  slightly  different  things.  

It's  complicated.  

But  it's  been  so  important  that  it's  been  almost  unchanged  since  bacteria.  

That's  how  ancient  this  is  and  that's  how  important  it  is.  

And  it  is  what  regulates  growth  or  not.  

And  when  you  keep  it  down,  you  up  regulate  maintenance  and  repair,  

that  translates  to  longevity.  

That's  what  we  want,  we  want  to  keep  it  down.  

But  we  know  that  it  began  with  bacteria,  

ancient  life  

and  it  senses  nutrient  availability,  

what  are  those  nutrients  that  it  evolved  with...  

Glucose  and  amino  acids.  

Those  where  the  components  and  fuel  necessary  to  replicate  life.  

You  keep  those  down  and  you  keep  all  these  other  things  down  

that  otherwise  would  increase  mTOR  and  prevent  this  up  regula3on  

of  the  gene3c  expression  of  maintenance  and  repair.  

It's  really  quite  elegant.  

We  know  that  TOR  is  also  largely  responsible  for  something  called  autophagy.  

Autophagy  is  really  important  -­‐  it  gets  rid  of  the  crap.  

So  if  you  have  malfunc3oning  proteins  in  your  cells,  

you  want  to  get  rid  of  them  before  you  can  make  new  ones.  

Just  like  we  purposely  try  and  break  down  our  bones  

so  that  we  can  rebuild  our  bones.  

You  have  to  get  rid  of  the  bad  proteins  to  replace  them  with  good  proteins.  

You  do  that  with  autophagy.  

Part  of  that  is  also  mitophagy  to  get  rid  of  bad  mitochondria,  

so  you  can  replace  it  with  good  mitochondria.  

That's  largely  controlled  by  mTOR.  

"mTOR  from  growth  signal  integra3on  to  cancer,  diabetes  and  aging  

"and  all  eukaryotes  -­‐  that's  us-­‐-­‐  the  target  of  rapamycin  

"signaling  pathway  couples  energy  and  nutrient  abundance  

"to  the  execu3on  of  cell  growth  and  division,  

"owing  to  the  ability  of  TOR  protein  kinase  

"to  simultaneously  sense  energy,  nutrients  and  stress,  

"and  in  metazoans  -­‐  meaning  animals  -­‐  growth  factors.  

"In  the  past  few  years  a  significant  advance  in  our  understanding  

"of  the  regula3on  and  func3ons  of  mTOR  

"has  revealed  the  crucial  involvement  of  this  signaling  pathway  

in  the  onset  and  progression  of  diabetes,  cancer  and  ageing."  

And  I  might  also  add  obesity.  

When  we  say  growth  factor,  when  mTOR  is  up  regulated,  

it  makes  you  fat  also.  

That's  kind  of  a  newer  associa3on  between  mTOR  and  health.  

Amino  acids  mediate  the  mTOR/raptor  signaling  

through  ac3va3on  of  phospha3dylinositol.  

"We  found  that  a  major  pathway  by  which  amino  acids  control  mTOR  signaling  

is  dis3nct  from  that  of  insulin."  

And  there  have  been  experiments  recently  to  determine  

what  are  the  most  powerful  signals  that  s3mulate  mTOR  

and  without  ques3on  the  most  powerful  signals  that  s3mulate  mTOR  

are  the  amino  acids.  

In  fact  there's  nothing  else  you  can  do  that  if  you  eat  excess  protein  

and  the  cells  were  exposed  to  excess  immuno  acids,  

you  can  be  good  about  everything  else  -­‐  

you  could  keep  glucose  down  and  insulin  down  and  IGF  down,  

and  mTOR  would  be  s3ll  elevated.  

That's  how  important  restric3ng  protein  is  

and  that's  why  I  say  now,  even  though  I  knew  20-­‐25  years  zero  

that  restric3ng  protein  was  important,  

now  I  would  say  it's  even  more  important  than  restric3ng  carbohydrates.  

And  here  we  have  it.  

"The  ra3o  of  macronutrients,  not  caloric  intake,  dictates  cardio  metabolic  health,  

aging  and  longevity  in  ad  libitum-­‐fed  mice"  

"Longevity  and  health  were  op3mized  when  protein  was  replaced  with  carbohydrate  

to  limit  compensatory  feeding  for  protein  and  suppress  protein  intake."  

"The  results  suggest  that  longevity  can  be  extended  in  animals  

"that  feed  whenever  they  want  to  

by  manipula3ng  the  ra3o  of  macronutrients  to  inhibit  the  mTOR  ac3va3on."  

Now  it  didn't  test  it  against  a  high-­‐fat  diet.  

This  was  strictly  tes3ng  carbohydrate  versus  protein.  

And  they  found  that  if  they  increased  the  carbohydrates,  

which  then  sa3ated  the  animal  enough  that  they  wouldn't  eat  extra  protein,  

they  lived  longer.  

In  other  words  protein  restric3on  was  more  important  than  carbohydrate  restric3on.  

There  is  a  drug  Novar3s  Afinitor.  

It  helps  women  with  advanced  breast  cancer  live  longer.  

The  protein  targets  mTOR  and  cancer  cells,  

a  protein  that  acts  as  an  important  regulator  of  tumor  cell  division,  

blood  vessel  growth  and  cell  metabolism.  

Resistance  to  hormonal  therapy  in  breast  cancer  

has  been  associated  with  over  ac3va3on  of  the  mTOR  pathway.  

And  I  might  add  now  that  almost  all  cancers  up  regulate  mTOR.  

So  we  don't  want  to  do  that.  

How  do  you  not  do  it?  

Restrict  protein.  

The  best  drug  to  reduce  mTOR  signaling,  to  slow  aging  

and  the  chronic  diseases  associated  with  it  is  present.  

You  don't  need  Afinitor.  

Reduce  your  protein  intake!  

It  doesn't  mean  that  I  want  you  to  eat  carbohydrates.  

No,  no,  no.  

What's  le@?  

Fat.  

You  want  to  eat  a  high-­‐fat  diet.  

These  are  really  compelling  reasons  for  that.  

Now  I  told  you  I  wanted  to  leave  you  a  liQle  bit  confused.  

So  far  I  have  just  giving  you  answers.  

I  can't  just  give  you  answers.  

First  we'll  talk  about  what's  high.  

I  used  to  say  about  a  gram,  protein  per  kilogram  of  lean  body  mass.  

In  other  words  es3mate  what  your  mass  is  without  any  fat  

and  as  a  fudge  factor,  

you  could  have  up  to  a  gram  of  protein  per  kilo  of  lean  mass  per  day.  

And  diabe3cs  I  would  give  0.75.  

What  I  would  say  now  is  that  everybody  should  have  0.75  

and  you  can  even  go  lower.  

Your  body  would  conserve  that  protein.  

You  will  lower  mTOR,  you  will  increase  maintenance  and  repair.  

And  you  will  be  healthier.  

Now  here  is  where  you'll  get  confused.  

Ketone  body  u3liza3on  drives  tumor  growth  and  metastasis.  

There  have  been  finding  and  this  actually  I  think  went  around  the  Paleo  community.  

And  everybody  were  scratching  their  heads  and  coming  up  

with  really  unfortunately  rather  bogus  excuses.  

I  think  that  Eric  Westman  had  the  best  comment  on  it  

when  he  said,  "Cancer  is  complicated."  

Yes  it  is.  

But  there  actually  is  an  answer  to  this.  

And  again  it's  not  going  to  ingra3ate  too  many  people...  

But  it's  not  ketogenesys  really  that  we  are  a@er.  

It's  fat  burning.  

They're  not  the  same  -­‐  it's  a  high-­‐fat  diet.  

It's  not  the  same.  

You  can  have  a  ketogenic  diet  by  ea3ng  high-­‐protein.  

It  isn't  the  ketones  necessarily  that  give  you  the  benefit.  

It's  the  fact  that  you  are  burning  fat.  

The  ketones  are  a  byproduct  so  you  have  to  specify  if  you're  going  to  say  

a  ketogenic  diet  it's  a  high-­‐fat  ketogenic  diet.  

And  it's  really  the  burning  of  the  high-­‐fat  that's  of  benefit,  

the  burning  of  the  faQy  acids.  

As  a  result  you  will  get  ketones  that  your  brain  needs.  

They  do  good  things  too  and  they  signal,  

but  you  don't  want  to  be  a@er  4+  ketones  in  the  blood.  

That's  not  what  you're  striving  for.  

That's  not  why  it's  a  good  diet.  

So  a  ketogenic  diet  is  a  good  diet,  but  not  because  it's  ketogenic.  

It's  because  it's  an  indica3on  that  you  are  burning  fat.  

And  I'm  going  to  just  to  take  ques3ons.